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Updates in Acanthamoeba Keratitis
Abstract
Acanthamoeba keratitis is a potentially blinding microbial disease that has been increasing in incidence during the past two decades. Prognosis of this serious disease had been dismal, but improvement in diagnosis, a better understanding of the natural course of the disease, and recent introduction of multiple and effective therapeutic agents have resulted in improvement of visual outcomes.
A review of literature pertaining to Acanthamoeba keratitis.
Contact lens wear and exposure to contaminated water sources remain the most important risk factors; however, in vivo confocal microscopy and improved biomicroscopic screening have proven instrumental in accurate early diagnosis. Complications of Acanthamoeba keratitis include dacryoadenitis, corneal melting and scarring, severe secondary glaucoma, cataract, and chronic anterior segment inflammation that can rarely lead to reactive blinding retinal ischemia. Combination chemotherapeutic agents have been shown to be more effective than monotherapy, whereas rehabilitative surgery such as penetrating keratoplasty is best performed on a quiet eye free of ocular inflammation and with no residual amoebae.
Increased suspicion by clinicians for Acanthamoeba and confocal microscopy have allowed more rapid and accurate diagnosis; treatment with multiple antiamoeba drugs is essential to disease resolution. Provided there are no residual amoebae after treatment, penetrating keratoplasty has been successful in visual rehabilitation. Secondary glaucoma occurs frequently and may require drainage procedures for control of intraocular pressure. Posterior complications are rare but may lead to ischemic retinitis.
... In approximately 23% of cases [62,[64][65][66], a mixed infection involving viruses, bacteria, or fungi is observed. Chuang et al. showed two cases of co-infection of Acanthamoeba with Pseudomonas (a contact-lens wearer presenting with a paracentral corneal ulcer and perineuritis) and microsporidia (presentation with multiple raised corneal lesions associated with epitheliitis): perineuritis in contact-lens wearers and epitheliitis in patients without risk factors are unusual presentations for AK and should raise suspicion of coinfection with other pathogens [67]. ...
... The initial stages within the first two weeks of infection exhibit alterations in the epithelial and subepithelial layers, characterized by the term "chameleon-like epithelial changes." These changes encompass features such as "dirty epithelium", pseudodendritiform epitheliopathy, epithelial microerosions, and microcysts [64][65][66]70,71]. ...
... These The initial stages within the first two weeks of infection exhibit alterations in the epithelial and subepithelial layers, characterized by the term "chameleon-like epithelial changes." These changes encompass features such as "dirty epithelium", pseudodendritiform epitheliopathy, epithelial microerosions, and microcysts [64][65][66]70,71]. ...
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.
... This trend of increasing cases was classified as outbreaks. [48][49][50] The Centers for Disease Control and Prevention (CDC, USA) suggested an association with complete Moisture Plus (Abbot Medical Optics, USA), but its recall did not result in any appreciable decline in CL-related AK. [17,51] Overall, since 2004, there has been a tenfold increase in AK, but it should be understood that it is still an uncommon cause of keratitis, affecting approximately 20 patients in 1 million CL wearers in a given year. [52] All types of CL have been implicated in AK, but the use of soft CL predominates. ...
... The observed clinical features vary according to the duration of symptoms prior to presentation. [38,51] Early disease, which includes punctate keratopathy, pseudodendrites, epithelial or subepithelial infiltrates, and perineural infiltrates, usually occurs within a month of onset of symptoms. Perineural infiltrates are considered pathognomonic and are believed to be due to the affinity of trophozoites for corneal nerves. ...
... Rarely, post-segment inflammation and ischemia can occur. [51] Although the severe inflammation that occurs in scleritis or posterior segment ischemia is considered to be an immune phenomenon, there have been reports of isolation of cysts from the vitreous and the sclera. [10] ...
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.
... The most widely accepted first-line treatments include a combination of two or three of the following topical therapies aimed at disrupting organism membranes: 0.1% propamidine isethionate, 0.02%-0.04% chlorhexidine, and 0.02% polyhexamethylene biguanide (PHMB) [10]. More concentrated doses of PHMB have demonstrated superior efficacy in locally advanced cases [10]. ...
... chlorhexidine, and 0.02% polyhexamethylene biguanide (PHMB) [10]. More concentrated doses of PHMB have demonstrated superior efficacy in locally advanced cases [10]. Greatest efficacy has been shown when doses are "pulsed" in a way that encourages excystment to the more susceptible trophozoite phase [10]. ...
... More concentrated doses of PHMB have demonstrated superior efficacy in locally advanced cases [10]. Greatest efficacy has been shown when doses are "pulsed" in a way that encourages excystment to the more susceptible trophozoite phase [10]. ...
Acanthamoeba species are free-living protozoa found pervasively in water and soil, which can cause infections of the central nervous system, skin, and eye. Amoebic keratitis (AK) is a vision-threatening, often chronic infection that is associated with the use of soft contact lenses due to corneal microtrauma and improper cleaning and storage. Although AK infections are rare, they cause significant morbidity including vision loss due to the diagnostic and therapeutic challenges they pose.
The clinical course is determined by the organism’s inherent pathogenicity, delay of diagnosis, and the paucity of data on effective therapeutic regimens. The case series and review of literature that follows examine current latest best practices in AK diagnosis including in vivo confocal microscopy (IVCM) and therapeutic interventions including miltefosine.
... studies revealed that different human populations are exposed to the non-pathogenic and pathogenic strains of Acanthamoeba [8][9][10][11][12][13]. Some FLA strains are facultative parasites causing Acanthamoeba keratitis (AK), a sight-threatening disease mainly reported as non-opportunistic disease in contact lens wearers and related to improper contact lens hygiene; the disease is detected with increasing frequency along with the spread of contact lens use [1,4,6,[11][12][13][14]. ...
... studies revealed that different human populations are exposed to the non-pathogenic and pathogenic strains of Acanthamoeba [8][9][10][11][12][13]. Some FLA strains are facultative parasites causing Acanthamoeba keratitis (AK), a sight-threatening disease mainly reported as non-opportunistic disease in contact lens wearers and related to improper contact lens hygiene; the disease is detected with increasing frequency along with the spread of contact lens use [1,4,6,[11][12][13][14]. A corneal epithelial injury and exposure of eye to water containing amoebic trofozoites or cysts are, apart from contact lens wear, other factors predisposing to AK. ...
... The proper diagnosis of the keratitis is difficult due to nonspecific symptoms, similar to those occurring in other eye diseases -in viral, fungal or bacterial keratitis. Treatment of AK is often unsuccessful because diagnostic mistakes delay an appropriate therapy [4,11,[13][14][15]. Exceptional high resistance of the Acanthamoeba cysts to chemicals and drugs is mentioned as the key contributors of treatment failure and a prolonged course of the disease, thus, different chemical agents were tested, also by us, and are still examined for their potential anti-amoebic in vitro activity against various species, strains/isolates of Acanthamoeba [4,[19][20][21][22][23][24]. ...
Small amoebae belonging to the Acanthamoeba genus complete their life cycles in different environmental niches as free-living protists however some of them are facultative parasites that can cause severe disease in humans. The sight-threatening Acanthamoeba keratitis develops in immune-competent persons, mainly in contact lens wearers; it is detected with increasing frequency along with the spread of contact lens use. The high abundance of the amoebae in the environment is important for dispersion and transmission of the infections among humans. Emerging threats for the public health generated by these amoebae is the serious medical problem worldwide. Nonspecific symptoms, similar to those occurring in the other eye diseases, diagnostic mistakes, the delay of an appropriate treatment, an exceptional high resistance of the amoebae to chemicals and drugs result in a prolonged course of the disease and often unsuccessful therapeutic management. Thus, different chemicals are still examined for their potential activity in vitro against various species, strains/isolates of Acanthamoeba. As the prolonged therapy often induces encystation subsequently leading to excystment and recurrences of amoebic keratitis, apart from anti-amoebic activity, cysticidal effect of examined agents is desirable. In the present study, results of our comparative investigations showed that cationic antiseptic chlorhexidine digluconate indicated in vitro anti-amoebic effect on environmental
Acanthamoeba castellanii Neff strain and pathogenic corneal Acanthamoeba polyphaga T4 genotype. Amoebostatic effect of the disinfectant was expressed in reduced number of surviving amoebae in comparison to the respective control cultures; simultaneously, despite prolonged incubation with the agent no stimulation of encystation was noted. The corneal strain was more resistant to the tested compound than the Neff strain. The cysticidal efficacy of chemicals is very expected, thus further in vitro studies on pathogenic Acanthamoeba strains with different application chemicals
pattern are needed.
... Acanthamoeba keratitis occurs worldwide and many AK outbreaks in both developed and developing countries have been reported 5) . The development of AK has been mostly linked to contact lens use 6,7) and also to the exposure to contaminated soil or water following trauma 8) . ...
... Important factors which may influence the in-vitro susceptibility testing involve the maintaining of cyst number against antimicrobial eye drop and the geographical distribution of Acanthamoeba strains 6,14) . Moreover, culturing conditions, kind of Acanthamoeba isolates, cysts storage time, procedures of drugs susceptibility test may also result in slight variations in MCC results 23) . ...
Introduction: Acanthamoeba keratitis (AK) is becoming an increasingly well-known clinical entity, resulting in corneal infections that are refractory to medical therapy. The Acanthamoeba species in their encysted state are resistant to antimicrobial agents and these render medical treatment difficult. Objective: This in-vitro susceptibility testing study was conducted to determine the effectiveness and the minimum cysticidal concentration (MCC) of 0.02% Chlorhexidine and 0.1% Propamidine isethionate (Brolene®) against four environmental isolates of Acanthamoeba ie; PHS 11, PHS 15, TLA 1 & KSA 13. Materials and Methods: The in-vitro susceptibility test adopted the method by Narasimhan et al. with slight modification. Briefly, serial doubling dilutions of the antimicrobial agents were performed in microtiter plates. After exposure of the Acanthamoeba cysts to the antimicrobial agents for 24 hours, the cysts were washed three times with PAS and centrifuged. The deposits (cysts) were cultured onto non-nutrient agar coated with heat-killed Escherichia coli. The excystment of trophozoites from cysts was observed and recorded microscopically for 14 days to determine the MCC value of each drug. Result: Chlorhexidine successfully exhibited cysticidal activities on all isolates while propamidine was effective on the majority of the isolates. The mean MCC values of Chlorhexidine and Propamidine were 10.9 μg/ml and 296.8 μg/ml respectively. Conclusion: Both Chlorhexidine and Propamidine are effective anti-Acanthamoeba agents and the combination is still suitable for the treatment of Acanthamoeba keratitis.
... A suitable animal model is vital for understanding the disease pathogenesis and to study drug effects. Few studies in the past have successfully developed AK models in rats, pigs, hamsters and rabbit using contact lenses [4][5][6][7]. Acanthamoeba tends to attach firmly to the plastic material, and non-siliconised glassware [8,9]; thus contact lenses have also been used to establish Acanthamoeba keratitis in various animal models [10,11]. However, the steep curvature and extremely small size of the mouse cornea makes it difficult for the contact lens to fit and as a result, it gets dislodged very early. ...
... Previous studies have used contact lenses of suitable size in different animal models to develop AK [6][7][8][9]25]. ...
Context
Acanthamoeba is increasingly implicated in causing keratitis in patients wearing contact lens or ocular trauma and has a poor prognosis. Establishment of an animal model is critical to study the disease pathology, pathogenesis and to evaluate anti-amoebic drugs. Some studies have used contact lenses to establish Acanthamoeba keratitis (AK) in a mouse model, which is expensive and not very successful as lenses get dislodged.
Objective
To assess the feasibility of using parafilm (Bemis Company Inc., USA) as an alternative to contact lens for the establishment of AK in the mouse model.
Methods
Thirty-six Balb/c mice in three groups of six mice each for two strains of Acanthamoeba were used to induce AK. Three experimental approaches used were; i) Acanthamoeba impregnated contact lens, ii) Acanthamoeba impregnated parafilm and iii) scratching followed by inoculation of Acanthamoeba suspension. In all three models, tarsorrhaphy was performed. Infection was evaluated by clinical examination and also through microscopic examination of corneal scrapings and corneal sections.
Results
AK model was successfully established with parafilm whereas only one mouse developed AK with the use of contact lens and none with scratching and Acanthamoeba inoculation.
Conclusion
The use of parafilm is convenient, reliable and cheaper and can be considered an alternative to contact lenses to induce AK in a mouse model.
... A canthamoeba is an amoebic parasite which targets immunocompromised patients causing central nervous system and skin infections. [1,2] However, it may involve the cornea in relatively healthy individuals. [2] One of the most known risk factors for acanthamoeba keratitis in western countries is wearing contact lenses (CL), while developing countries usually presents as a result of trauma or water exposure. ...
... [1,2] However, it may involve the cornea in relatively healthy individuals. [2] One of the most known risk factors for acanthamoeba keratitis in western countries is wearing contact lenses (CL), while developing countries usually presents as a result of trauma or water exposure. [1,3] The clinical suspension of acanthamoeba keratitis is the most important step in the diagnosis which leads to early detection and better outcome. ...
We are reporting the case of a 25-year-old female who developed acanthamoeba keratitis after wearing contact lenses for high myopia. She was diagnosed as acanthamoeba and started the treatment of antiacanthamoeba for 3 consecutive weeks, followed by bare Descemet's therapeutic lamellar keratoplasty (LKP) with the maintenance of antiacanthamoeba treatment to control the infection. In the late postoperative period, visual rehabilitation was obtained by insertion of implantable Collamer lens (ICL) with her final visual outcome was 20/30. For acanthamoeba keratitis, early bare Descemet's therapeutic LKP has a better outcome in comparison to late penetrating keratoplasty in terms of infection eradication and globe preservation. After removal of all sutures, the refractive error can be corrected with photorefractive procedures as well as ICL.
... Acanthamoeba spp. can also cause amebic keratitis, a severe, unrelenting disease among contact lens wearers, that often necessitates corneal transplantation and can result in blindness (Awwad et al., 2007). ...
... High physician vigilance and awareness of the epidemiologic factors are essential. In addition, tissue samples (CSF or brain biopsy for PAM and GAE), skin biopsies (for disseminated Acanthamoeba or Balamuthia infection), or corneal scrapings (for Acanthamoeba keratitis) are often needed (Awwad et al., 2007). Specialized diagnostic tests for parasite identification done at the CDC can also be helpful (CDC, 2017). ...
The free-living amebae Naegleria, Acanthamoeba, and Balamuthia cause rare but life-threatening infections. All three parasites can cause meningoencephalitis. Acanthamoeba can also cause chronic keratitis and both Balamuthia and Acanthamoeba can cause skin and systemic infections. There are minimal drug development pipelines for these pathogens despite a lack of available treatment regimens and high fatality rates. To identify anti-amebic drugs, we screened 159 compounds from a high-value repurposed library against trophozoites of the three amebae. Our efforts identified 38 compounds with activity against at least one ameba. Multiple drugs that bind the ATP-binding pocket of mTOR and PI3K are active, highlighting these compounds as important inhibitors of these parasites. Importantly, 24 active compounds have progressed at least to phase II clinical studies and overall 15 compounds were active against all three amebae. Based on central nervous system (CNS) penetration or exceptional potency against one amebic species, we identified sixteen priority compounds for the treatment of meningoencephalitis caused by these pathogens. The top five compounds are (i) plicamycin, active against all three free-living amebae and previously U.S. Food and Drug Administration (FDA) approved, (ii) TG02, active against all three amebae, (iii and iv) FDA-approved panobinostat and FDA orphan drug lestaurtinib, both highly potent against Naegleria, and (v) GDC-0084, a CNS penetrant mTOR inhibitor, active against at least two of the three amebae. These results set the stage for further investigation of these clinically advanced compounds for treatment of infections caused by the free-living amebae, including treatment of the highly fatal meningoencephalitis.
... [2,3] Since then, many authors have published their experience with this disease and information has been compiled in review articles. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Thus, there has been substantial growth in the knowledge about the disease. However, nearly all review articles on this topic have been published from the Western world with primary focus on contact lens (CL)-associated keratitis. ...
... [50,51] Biguanides and diamidines have the best in vitro cysticidal activity and their use in clinical practice for the treatment of AK is supported by the vast in vivo experience in peer-reviewed literature. [4][5][6][7][8][52][53][54][55][56][57] Therefore, topical biguanides with or without the addition of diamidines are the main stay of medical management of this disease. At our center, a combination of PHMB 0.02% and chlorhexidine 0.02% is used as the primary therapy. ...
The purpose of the study is to describe epidemiology, clinical features, diagnosis, and treatment of Acanthamoeba keratitis (AK) with special focus on the disease in nonusers of contact lenses (CLs). This study was a perspective based on authors' experience and review of published literature. AK accounts for 2% of microbiology-proven cases of keratitis. Trauma and exposure to contaminated water are the main predisposing factors for the disease. Association with CLs is seen only in small fraction of cases. Contrary to classical description experience in India suggests that out of proportion pain, ring infiltrate, and radial keratoneuritis are seen in less than a third of cases. Majority of cases present with diffuse infiltrate, mimicking herpes simplex or fungal keratitis. The diagnosis can be confirmed by microscopic examination of corneal scraping material and culture on nonnutrient agar with an overlay of Escherichia coli. Confocal microscopy can help diagnosis in patients with deep infiltrate; however, experience with technique and interpretation of images influences its true value. Primary treatment of the infection is biguanides with or without diamidines. Most patients respond to medical treatment. Corticosteroids play an important role in the management and can be used when indicated after due consideration to established protocols. Surgery is rarely needed in patients where definitive management is initiated within 3 weeks of onset of symptoms. Lamellar keratoplasty has been shown to have good outcome in cases needing surgery. Since the clinical features of AK in nonusers of CL are different, it will be important for ophthalmologists to be aware of the scenario wherein to suspect this infection. Medical treatment is successful if the disease is diagnosed early and management is initiated soon.
... The hallmarks of AK include ring infiltrate, radial keratoneuritis, and disproportionate pain. [31,[39][40][41] Patients usually present with unilateral disease; however, it may be bilateral in up to 7.5% of patients, especially in CL wearers associated with poor lens hygiene. [42] The disease classically starts as an epithelial lesion and progresses to involve the stroma. ...
Acanthamoeba keratitis (AK) generally displays a protracted course with significant morbidity. This is partly due to the fact that it is often misdiagnosed as viral or fungal keratitis. It is associated most with contact lens (CL) wear in developed countries, and exposure to soil or unsanitary water in the developing countries. The textbook description of AK includes the presence of ring infiltration, radial keratoneuritis, and disproportionate pain. Of the patients that presented to our tertiary care center, only 40% had a history of CL use, and 33% had a ring infiltrate. Corneal scraping for microbiological culture on non-nutrient agar serves as the gold standard for diagnosis. Corneal biopsy and confocal microscopy hold diagnostic value in deeper lesions, and polymerase chain reaction and newer molecular techniques are emerging as rapid and effective tools. Biguanides are the drug of choice for AK. But it is important to reconstitute these drugs in correct dosages; otherwise, corneal toxicity can take place. The use of corticosteroids in AK is a matter of debate. We have used corticosteroids in cases with persistent keratitis, severe pain, and extra-corneal manifestations under the cover of amoebicidal therapy. Surgical intervention in the acute phase is reserved for advanced AK with limbus encroachment, perforations, or fulminant corneal abscesses. AK is thus a severe, potentially blinding disease, where a prompt diagnosis ensuring the timely commencement of amoebicidal therapy is an essential component of improving the patient’s prognosis. In this article, we have discussed the presentation, challenges in diagnosis and management, and our experience in managing AK.
... The genus Acanthamoeba has become a major threat to human health in Zimbabwe. 1 It has become the cause of life-threatening Granulomatous Amoebic Encephalitis (GAE), pulmonary infections, cutaneous lesions, rhinosinusitis, and osteomyelitis in immunocompromised people and those who wear contact lenses. 2 It is also the cause of Acanthamoeba Keratitis (AK), which causes severe corneal damage to those who put on contact lenses and swim in hot pools and to immunocompromised patients, such as those with Acquired Immune Deficiency Syndrome (AIDS), systemic lupus erythematosus, transplanted organ and those undergoing chemotherapy for cancer. 3 AK leads to permanent impaired vision and sometimes complete eye damage. ...
Acanthamoeba species are the major cause of Acanthamoeba Keratitis (AK) of eyes, Acanthamoeba meningoencephalitis of the central nervous system, and fatal Granulomatous Amoebic Encephalitis (GAE) of the brain in humans. These diseases are difficult to treat due to their resistance to extreme temperatures, pH, alcohol, and pressure. This research aimed to determine the anti-amoebic effects of some selected plant extracts against Acanthamoeba species isolated from borehole water samples from Budiriro District, Harare, Zimbabwe. Acanthamoeba castellannii species were isolated and confirmed present in Budiriro borehole water samples using non-nutrient agar, microscope, real-time Polymerase Chain Reaction (PCR), and gel electrophoresis. The selected plant samples, Murumanyama (Xeroderris stuhlmannii) bark extract, Munhundurwa (Solanum incanum) fruit extract and Mufandichimuka (Myrothamnus flabellifolius) stem and leaf extracts were then investigated for their anti-amoebic effects against the isolated Acanthamoeba castellannii, using agar well diffusion method. Chlorhexidine gluconate antibiotic was used as a control. The results show that Acanthamoeba castellannii is the most common Acanthamoeba species in borehole water in Budiriro District in Harare and all the tested plant samples had no anti-amoebic effects against this isolated Acanthamoeba castellannii.
... In 1985, Wright et al. reported the first medical cure using a combination of topical neomycin and propamidine isethionate (Brolene ® ) [20]. Since then, medical treatments with propamidines and biguanides have revolutionized the treatment of AK with good success rates and relatively few side effects [13,[21][22][23]. Approximately 75% of AK cases can be successfully treated medically with a good visual acuity and without the need for future KP [24]. ...
Background: Early therapeutic penetrating keratoplasty (TKP) for Acanthamoeba keratitis (AK) is thought to have a worse visual prognosis than the delayed optical penetrating keratoplasty (OKP) after successful conservative treatment of AK. This has led to a tendency to prolong conservative therapy and delay penetrating keratoplasty in patients with AK. This retrospective series presents the results of patients with AK that underwent early penetrating keratoplasty after reducing the corneal amoeba load through intensive conservative therapy, so-called “low load keratoplasty” (LLKP). Patients and methods: The medical records of our department were screened for patients with AK, confirmed by histological examination and/or PCR and/or in vivo confocal microscopy, which underwent ab LLKP and had a follow-up time of at least one year between 2009 and 2023. Demographic data, best corrected visual acuity (BCVA) and intraocular pressure at first and last visit, secondary glaucoma (SG), and recurrence and graft survival rates were assessed. Results: 28 eyes of 28 patients were included. The average time from initiation of therapy to penetrating keratoplasty (PKP) was 68 ± 113 days. The mean follow-up time after LLKP was 53 ± 42 months. BCVA (logMAR) improved from 1.9 ± 1 pre-operatively to 0.5 ± 0.6 at last visit (p < 0.001). A total of 14% of patients were under medical therapy for SG at the last visit, and two of them underwent glaucoma surgery. The recurrence rate was 4%. The Kaplan–Meier graft survival rate of the first graft at four years was 70%. The second graft survival rate at four years was 87.5%. Conclusion: LLKP appears to achieve a good visual prognosis with an earlier visual and psychological habilitation, as well as low recurrence and SG rates. These results should encourage us to reconsider the optimal timing of PKP in therapy-resistant AK.
... The symptoms of AK include severe eye pain, redness, blurred vision, sensitivity to light, and excessive tearing. 6,7 The infection can progress rapidly and can cause permanent damage to the cornea if left untreated. ...
keratitis (AK) is a severe and potentially blinding corneal infection caused by the protozoan . Despite its rare occurrence, AK poses significant challenges in diagnosis, treatment, and management due to its complex pathogenesis and resistance to conventional therapies. Experimental models have played a crucial role in deepening our understanding of the disease and developing novel therapeutic strategies. This abstract review the various experimental models utilized to study keratitis. These models encompass both in vitro and in vivo systems, enabling researchers to simulate the pathogenic processes involved and evaluate potential therapeutic interventions. , models include cell cultures, corneal epithelial cell lines, and three-dimensional corneal constructs. These systems allow the investigation of adhesion, invasion, host immune responses, and drug efficacy. They provide insights into the molecular mechanisms underlying pathogenesis and aid in the screening of potential anti- agents. models, including animal models such as rabbits and mice, mimic the clinical manifestations of AK and provide a platform for assessing disease progression, evaluating host immune responses, and testing therapeutic interventions. These models have been instrumental in elucidating the factors influencing pathogenesis, including host susceptibility, immune responses, and corneal tissue interactions. Overall, experimental models of keratitis have significantly contributed to our understanding of the disease and provided a platform for developing and evaluating novel treatment strategies. The insights gained from these models hold promise for developing more effective therapies, aiming to improve patient outcomes and mitigate the devastating consequences of keratitis.
... 67 Contaminated water exposure increases the risk of microbial keratitis in contact lens wearers (Figure 3), in particular Acanthamoeba keratitis. 68 Therefore, recommendations should be made for daily contact lens wear over monthly or extended wear lenses and advice against swimming, showering or sleeping in contact lenses should be provided to all potential travellers. Prescription swimming goggles should also be considered. ...
Rationale for review:
Eye diseases pose a significant public health and economic burden, particularly for travellers exposed to ocular hazards who may lack access to specialist eye care. This article offers an evidence-based review for travel-health practitioners, with a particular emphasis on ocular infections and trauma that are more prevalent among travellers. Providing an overview of these issues will allow travel health practitioners to comprehensively address ophthalmic considerations of travel.
Methods:
A systematic literature search was conducted on PubMed and Embase electronic databases, using keywords related to travel medicine and ophthalmology. Inclusion was based on the relevant contribution to epidemiology, aetiology, diagnostics, management, and long-term consequences of travel-related eye conditions. The data were analysed using narrative synthesis.
Key findings:
This literature review highlighted that various travel-related eye conditions may occur. Travellers should be aware of the risk of travel-related ocular complications, which can arise from ocular infections, high-risk activities, high altitude and space travel. The economic and logistical challenges associated with medical tourism for ophthalmic procedures are discussed. For travellers with pre-existing eye conditions or visual impairment, careful planning may be needed to promote eye health and ensure safety of travel.
Conclusions:
Travel medicine practitioners should have a comprehensive understanding of the major ocular risks associated with overseas travel, including eye infections, eye injuries and solar eye damage. Further research in this area can enhance overall wellness and alleviate the burden of ocular diseases on travellers. Evidence-based guidelines based on research can also improve the quality of care and prevent long-term vision problems.
... 3,4 Acanthamoeba trophozoites and cysts can spread to the limbus and sclera, and overwhelming infection and inflammation may lead to a painful, blind eye, resulting in need for enucleation. 5,6 Surgical approaches include epithelial debridement, cryotherapy, deep anterior lamellar keratoplasty (DALK), and penetrating keratoplasty (PKP). 3,7 Among these procedures, therapeutic PKP has the potential advantage of debulking all the cysts from the corneal tissue. ...
Purpose:
The purpose of this study was to report a novel approach of prepenetrating keratoplasty (PKP) corneal map biopsies to define the extent of Acanthamoeba cyst infiltration in recalcitrant Acanthamoeba keratitis.
Methods:
Corneal map biopsies were performed 1 week before PKP. Four biopsies, 1 from each peripheral corneal quadrant, were obtained to delineate the extent of microscopic infection. Histological results of these map biopsies were used to determine the size and location of the subsequent PKP.
Results:
In our first case, map biopsies revealed Acanthamoeba cysts in 2 of the 4 biopsies. This led to an inferotemporally eccentric 8.5-mm PKP. The final histology report indicated that the closest resection margin was 0.08 mm. In our second case, the peripheral map biopsies were clear and an inferiorly eccentric 8.25-mm PKP was performed. The final histology report indicated that the closest resection margin was 2.3 mm. Both grafts have remained clear at 6 months postoperatively.
Conclusions:
Map biopsies of the cornea can achieve total removal of the corneal tissues infested with Acanthamoeba cysts and prevent reinfection of the donor graft.
... İmmün sistemi baskılanmış bireylerde hayatı tehdit eden granülomatöz amibik ensefalite (GAE) ve kontakt lens kullananlarda görmeyi tehdit eden amip keratitine neden olan bu protozoon son zamanlarda daha fazla dikkat çekmeye başlamıştır. Nitekim, son yıllarda GAE kaynaklı ölüm oranları ve keratite bağlı göz hasarları vakalarında artış gözlemlenmiştir (1,2). Acanthamoeba türlerinin tanımlama ve alt cins düzeyinde klasifikasyonunda sıkıntılar bulunmaktadır. ...
Bu çalışma, farklı su kaynaklarından elde edilmiş Acanthamoeba türlerinin moleküler prevalanslarının saptanması ve 18S rRNA gen bölgesine göre filogenetik karakterlerinin belirlenmesi amacıyla gerçekleştirilmiştir. Çalışmada, Sinop ve Ordu yörelerindeki çeşme suyu, havuz suları, kaplıca ve göllerden 80 örnek toplanmıştır. Su örneklerinin kültür ortamında üretilmesini takiben, DNA izolasyonu ve PCR analizleri gerçekleştirilmiştir. 18S rRNA gen bölgesi yönünden pozitif belirlenen amplikonlar klonlanmış ve plazmid pürifikasyonu yapılmıştır. Plazmidler vektör spesifik primerlerle sekanslanarak hedef dizilimler elde edilmiştir. İlgili sekanslarla birlikte GenBank veri tabanında kayıtlı benzer izolatları içeren toplam 31 sekanslık veri seti oluşturulmuştur. Çalışmada, Sinop yöresinde %17,1, Ordu yöresinden %20 Acanthamoeba pozitifliği tespit edilmiştir. Filogenetik incelemelerde, elde edilen Acanthamoeba izolatlarının Türkiye’den ve dünyadan rapor edilen T4 genotipine ait izolatlarla aynı kümede kümelendikleri görülmüştür. İzolatlar arasında iki haplotip saptanmış ve ortalama haplotip diversitesi 0,682±0,084 olarak belirlenmiştir. 18S rRNA veri setinde, TRERUAcantha1 ve TRERUAcantha2 haplotiplerinin de bulunduğu T4 genotipindeki tüm izolatların %100 identik oldukları belirlenmiştir. Filogenetik analizlerde T4 genotipindeki izolatların monofiletik yapılanma gösterdiği saptanmıştır. T4 genotipinde oldukları saptanan izolatlarımızın %99,9 ile Almanya’da kontakt lensten izole edilen ve T13 genotipinde yer alan KaBo (KJ476522) izolatıyla en yakın benzerliği gösterdiği görülmüştür.
... 85,88 Clinical symptoms of acanthameba keratitis include pseudodendritiform epitheliopathy, epithelial microerosions, microcysts, multifocal stromal infiltrates, and ring infiltrate. 89,90 Acanthameba keratitis is usually misdiagnosed and treated as herpetic, bacterial, or mycotic keratitis due to the similarity of several clinical signs and symptoms. Diamidines such as propamidine-isethionate (Brolene), hexamidinediisethionate (Hexacyl), and dibromopropamidine are administered at a concentration of 1%. ...
Keratitis is a disease characterized by inflammation of the cornea caused by different pathogens. It can cause serious visual morbidity if not treated quickly. Depending on the pathogen causing keratitis, eye drops containing antibacterial, antifungal, or antiviral agents such as besiloxacin, moxifloxacin, ofloxacin, voriconazol, econazole, fluconazole, and acyclovir are used, and these drops need to be applied frequently due to their low bioavailability. Studies are carried out on formulations with extended residence time in the cornea and increased permeability. These formulations include various new drug delivery systems such as inserts, nanoparticles, liposomes, niosomes, cubosomes, microemulsions, in situ gels, contact lenses, nanostructured lipid carriers, carbon quantum dots, and microneedles. Ex vivo and in vivo studies with these formulations have shown that the residence time of the active substances in the cornea is prolonged, and their ocular bioavailability is increased. In addition, in vivo studies have shown that these formulations successfully treat keratitis. However, it has been observed that fluoroquinolones are used in most of the studies; similar drug delivery systems are generally preferred for antifungal drugs, and studies for viral and acanthameba keratitis are limited. There is a need for new studies on different types of keratitis and different drug active substances. At the same time, proving the efficacy of drug delivery systems, which give promising results in in vivo animal models, with clinical studies is of great importance for progress in the treatment of keratitis.
... Broad-spectrum antibiotics are the current mainstay of treatment, though some studies have reported the potential use of topical alcohol in superficial Acanthamoeba keratitis (AK) and Pythium keratitis [72,73]. Early AK typically presents with punctate keratitis, epithelial and subepithelial infiltrates and pseudodendrites [74,75]. Most of the acanthamoebae are confined to the epithelial layer in the initial stages, which progresses to stromal involvement when the disease remains untreated [76]. ...
Alcohol (ethanol) has been used in medicine since time immemorial. In ophthalmic practice, besides as an antiseptic, it was given as retrobulbar injections to relieve severe ocular pain. Alcohol can be applied topically to the surface of neoplastic or suspicious lesions to kill cells that might desquamate and seed during surgical excision, to treat epithelial ingrowth that can occur following corneal surgeries, particularly laser in situ keratomileusis (LASIK), and to treat superficial infectious keratitis. In view of its ability to achieve a smooth cleavage plane between the epithelium and the Bowman's layer, alcohol-assisted delamination (ALD) of the corneal epithelium has been used widely and effectively for a variety of diagnostic and therapeutic indications, at times delivering both outcomes. Diagnostically, ALD yields an intact epithelial sheet which can be fixed flat to provide excellent orientation for histopathological evaluation. Therapeutically, it is most commonly used to treat recurrent corneal erosion syndrome, where its efficacy is comparable to that of phototherapeutic keratectomy but with several advantages. It has also been used to treat various forms of epithelial/anterior stromal dystrophies, which can obviate or delay the need for corneal transplantation for several years. In addition, ALD is performed in corneal collagen cross-linking and corneal refractive surgery for relatively atraumatic removal of the epithelium. In this review, we aimed to provide a comprehensive overview of the diagnostic and therapeutic use of topical alcohol in ophthalmology, to describe the surgical and fixation techniques of ALD, and to highlight our experience in ALD over the past decade.
... De éstas, la QA es la manifestación clínica más frecuente, principalmente en personas inmunocompetentes usuarios de lentes de contacto (7) , reportándose que 1 de cada 1500 usuarios de lentes de contacto, en el transcurso de 30 años de uso, pueden desarrollar úlcera corneal. Actualmente, se reconoce el incremento de las úlceras corneales producidas por amibas del género Acanthamoeba, en diferentes partes del mundo (8) . ...
Dentro del género Acanthamoeba existen especies relacionadas con patologías presentes en
los humanos. Su identificación y clasificación se realizaba por morfología, pero es subjetiva y
de baja sensibilidad y especificidad. Por ésto, es importante incorporar herramientas de biología
molecular. El objetivo de esta investigación fue caracterizar molecular y morfológicamente 24
aislados de Acanthamoeba, mantenidos en el Laboratorio de AmibiasisEscuela
de BioanálisisUCV,
mediante PCRRFLP
(HinffI, HhaI y HaeIII), previamente identificados morfológicamente
como Acanthamoeba (Pussard y Pons 1977). Ningún aislado perteneció al grupo I. De los 24
aislados, 45,8% presentó características morfológicas compatibles con el grupo II, 45,8% con el
grupo III y 8,4% con ambos grupos. Molecularmente, 50% de los aislados amplificaron
productos de 900 pb y 50% de 700 pb. Los aislados del grupo III, no se pudieron caracterizar
molecularmente por PCRRFLP,
ya que el patrón de digestión no coincidió con patrones
previamente publicados. Solo se identificó el 33% de los aislados resultando: A. polyphaga (A9,
A12, A13, A14), A. castellanii (A26, A27, A28 y A29) y A. castellanii o A. polyphaga (A15, A25
y A30). Las especies identificadas coinciden con las patógenas más comúnmente descritas en
la literatura.
... [41][42][43] The patients' presentations can vary and may involve common signs of ocular inflammation, such as blurred vision, photophobia, pain, and tearing, usually involving one eye but occasionally both. 44 Many articles have emphasized the degree of pain associated with AK and have even regarded it as the hallmark symptom; the pain has been described as "severe or excruciating" or "characteristically disproportionate to relatively mild clinical findings." 9 However, the diagnosis of AK cannot be ruled out if pain is absent. ...
Acanthamoeba keratitis (AK) is a rare but severe ocular infection with a significant risk of vision loss. Contact lens use is the main risk factor for AK. The orthokeratology (OK) lens, a specially designed contact lens, has been used worldwide as an effective method of myopia control. However, the OK lens is associated with an increased risk of Acanthamoeba infection. Many primary practitioners are concerned about this infection because of its relative rarity, the lack of promising therapeutic medications, and the need for referral. We herein report two cases of AK associated with OK lenses, present a systematic review of such cases, and discuss the possible reasons for the higher incidence rate of this infection in patients who wear OK lenses. We combined the clinical knowledge and skills of corneal specialists and lens experts with the sole objective of addressing these OK lens-related AK cases. We found that the most common risk factors were rinsing the lenses or lens cases with tap water. Prompt and accurate diagnosis along with adequate amoebicidal treatment are essential to ensure desirable outcomes for OK lens wearers who develop AK. Appropriate OK lens parameters and regular checkups are also important.
... Infection recurrence due to Acanthamoeba excystment occurs in approximately 10% of cases. Complications of AK include dacryoadenitis, corneal melting and scarring, severe secondary glaucoma, and chronic anterior segment inflammation [8]. Scleral inflammation, often referred to as sclerokeratitis, may also develop [9]. ...
Acanthamoeba keratitis (AK) can occur in healthy individuals wearing contact lenses and it is a painful, blinding infection of the cornea caused by a free-living ameba Acanthamoeba. Current treatment for AK relies on a combination of chlorhexidine, propamidine isethionate, and polyhexamethylene biguanide. However, the current regimen includes an aggressive disinfectant and in 10% of cases recurrent infection ensues. Therefore, development of efficient and safe drugs is a critical unmet need to avert blindness. Acanthamoeba sterol biosynthesis includes two essential enzymes HMG-CoA reductase (HMGR) and sterol 14-demethylase (CYP51), and we earlier identified a CYP51 inhibitor isavuconazole that demonstrated nanomolar potency against A. castellanii trophozoites. In this study, we investigated the effect of well-tolerated HMGR inhibitors and identified pitavastatin that is active against trophozoites of three different clinical strains of A.castellanii. Pitavastatin demonstrated an EC50 of 0.5 to 1.9 µM, depending on strains. Combination of pitavastatin and isavuconazole is synergistic and led to 2- to 9-fold dose reduction for pitavastatin and 11- to 4000-fold dose reduction for isavuconazole to achieve 97% of growth inhibition. Pitavastatin, either alone or in combination with isavuconazole, may lead to repurposing for the treatment of Acanthamoeba keratitis.
... Bei jedem 2. Patienten zeigen sich Epithelveränderungen wie Epithelunruhe, epitheliale Trübungen (sog. "dirty epithelium"), epitheliale Mikroerosionen oder Mikrozysten innerhalb der ersten beiden Wochen [9] (▶ Abb. 2 a). Im Gegensatz zur Keratitis dendritica herpetischer Genese fehlen bei der klassischen "pseudodendritiformen Epitheliopathie" der Akanthamöbenkeratitis die terminalen kölbchenartigen Auftreibungen [10]. ...
Zusammenfassung
Die Akanthamöbenkeratitis ist ein „Chamäleon“. Sie präsentiert sich klassischerweise mit gräulichen Epithelveränderungen, Perineuritis, oberflächlichen multifokalen stromalen Infiltraten und Ringinfiltrat. Bei klinischem Verdacht auf Akanthamöbenkeratitis ist eine Polymerase-Ketten-Reaktion, eine Kultivierung oder die histopathologische Untersuchung zur Diagnosestellung notwendig. Die konfokale Mikroskopie hat sich als noninvasive Ad-hoc-Diagnostik bei Initialverdacht instituiert.
... An effective animal model is currently being sought for the study of infectious keratitis of a mixed nature, which is essential for the progress of the treatment of such coinfections. However, obtaining a method to accurately identify etiological agents during the early stages is proving to be a challenge for researchers in this field [43,44]. Ocular infection models have been described in rabbits, mice, and rats, but many aspects of pathogenesis are currently unknown. ...
... However, the incidence of AK has gradually increased because Acanthamoeba has a widespread distribution in the environment while contact lens use is increasing [2,3]. AK is a painful corneal infection that may lead to vision loss or enucleation [4]. The first critical step in the pathogenesis of infection is its adhesion to the surface of host tissues. ...
Pathogenic Acanthamoeba spp. cause granulomatous amoebic encephalitis and keratitis. Acanthamoeba keratitis (AK) is a rare but serious ocular infection that can result in permanent visual impairment or blindness. However, pathogenic factors of AK remain unclear and treatment for AK is arduous. Expression levels of proteins secreted into extracellular space were compared between A. castellanii pathogenic (ACP) and non-pathogenic strains. Two-dimensional polyacrylamide gel electrophoresis revealed 123 differentially expressed proteins, including 34 increased proteins, 7 qualitative increased proteins, 65 decreased proteins, and 17 qualitative decreased proteins in ACP strain. Twenty protein spots with greater than 5-fold increase in ACP strain were analyzed by liquid chromatography triple quadrupole mass spectrometry. These proteins showed similarity each to inosine-uridine preferring nucleoside hydrolase, carboxylesterase, oxygen-dependent choline dehydrogenase, periplasmic-binding protein proteinases and hypothetical proteins. These proteins expressed higher in ACP may provide some information to understand pathogenicity of Acanthamoeba.
... Acanthamoeba keratitis (AK) is a potentially sight-threatening infection caused by several types of amoeba of the genus Acanthamoeba. 1 In recent years, AK has been increasing in prevalence, and outbreaks attributable to the use of certain types of contact lenses and cleaning solutions have been recorded. 2,3 The traditional treatments for AK are topical medications such as biguanides (0.02% chlorhexidine or 0.02% polyhexamethylene biguanide [PHMB]) and diamidines (0.1% propamidine isethionate); for those who fail topical treatments, surgical interventions such as therapeutic penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty are undertaken. ...
Purpose
The aim of this study was to evaluate the long-term outcomes of ethanol pretreatment in Acanthamoeba keratitis (AK).
Patients and methods
This single-center, retrospective, interventional study included 22 patients (24 eyes) who developed AK and underwent ethanol pretreatment between 2009 and 2015. Samples for smears, polymerase chain reaction, and culture for evidence of Acanthamoeba were collected. After ethanol pretreatment, the patients were treated with corneal epithelial debridement, topical 0.02% polyhexamethylene biguanide, and 0.1% propamidine isethionate. The primary outcomes were a clinically stable ocular surface, complete recovery from corneal infection, and acceptable corneal haze. The secondary outcome measure was improvement in best-corrected visual acuity. Complications and predictors of the visual outcome were also recorded.
Results
Ethanol pretreatment was successful in 20 (83.3%) of the 24 eyes, and no further optical keratoplasty was required. Four eyes required rescue therapeutic keratoplasty because of rapid progression of AK. Patients in whom ethanol pretreatment was successful achieved good final visual outcomes regardless of sex, age, or causative Acanthamoeba species. Patients with worse initial best-corrected visual acuity and rigid gas permeable lens-related AK had better improvement in vision.
Conclusion
Ethanol as a pretreatment for AK is safe and effective. Combined with corneal epithelial debridement, ethanol pretreatment may preclude the need for optical and therapeutic keratoplasty. This technique is suitable for all stages of AK presenting within 3 weeks of symptom onset and achieves favorable results especially in early AK.
... The common risk factor for the development of Acanthamoeba keratitis is contact lens wear and it is estimated about 85% of patients being contact lens wearers (Awwad et al. 2007), while about 10% of cases occur following trauma and exposure to contaminated soil or water (Dart 1995). There are about 80 million contact lens wearers throughout the world in 2000 and in Malaysia it is worn by about 5% of the population, which may increase the rate of infection (Barr et al. 2000;Anne 2001). ...
Introduction: Acanthamoeba spp. are free-living protozoan parasites that can cause painful, severe ocular inflammation and sight-threatening keratitis. Acanthamoeba keratitis is a widespread infectious corneal disease that has been reported worldwide. Objective: This study investigates the effectiveness and the range of minimum cysticidal concentration (MCC) of four antimicrobial agents in therapeutic doses; 0.02% chlorhexidine, 0.1% propamidine isethionate (Brolene®), 0.3% ciprofloxacin and 0.3% gentamicin against 4 clinical isolates of Acanthamoeba. Four isolates of Acanthamoeba cysts being used were derived from clinical cases (HKL 95, HKL 109, HS 5 and HS 6). Materials and methods: Serial doubling dilutions of the antimicrobial agents were performed in microtiter plates. After exposure of the four Acanthamoeba isolate cysts to the four antimicrobial agents for 24 hours, the cysts were washed three times with PAS and centrifuged. The deposits (cysts) were cultured onto non-nutrient agar coated with heat-killed Escherichia coli. The excystment of trophozoites from cysts was observed and recorded microscopically for 14 days to determine the MCC value of each drug. Results: Results of this study showed that chlorhexidine, propamidine isethionate, ciprofloxacin and gentamicin successfully exhibited their cysticidal activities in therapeutic doses on all isolates. The values of MCC for chlorhexidine, propamidine isethionate, ciprofloxacin and gentamicin varied from 6.25 to 25 μg/ml, 125 to 250 μg/ml, 1500 to 3000 μg/ml and 1500 to 3000 μg/ml, respectively. Moreover, chlorhexidine, propamidine isethionate, ciprofloxacin and gentamicin were found to exhibit cysticidal activities with their mean MCC values of 17.2 ± 9.4 μg/ml, 156.3 ± 62.5 μg/ml, 2625 ± 750 μg/ml and 1875 ± 750 μg/ml, respectively. Conclusion: The in vitro sensitivity test can be used as a standard test to determine values of MCC of drugs on Acanthamoeba isolates and to study the susceptibility pattern of anti-Acanthamoeba drugs. Chlorhexidine and Propamidine isethionate exhibited the best anti-Acanthamoeba activity and are therefore highly recommended for use in the treatment of Acanthamoeba keratitis. © 2018 Japan Health Sciences University & Japan International Cultural Exchange Foundation.
... Acanthamoeba keratitis (AK) is a rare, visual-threatening condition which has increased in recent years due to wearing soft contact lens. 1 Acanthamoeba is a protozoa found in soil, fresh and sea water, and in contact lens cleaning solutions. 2 A strong association has been established between AK and contact lens use. 3 The major risk factors for developing AK comprise epithelial microtrauma, contact lens overuse, improper contact lens maintenance, contact lens wear in contaminated water such as the swimming pool, and exposure to contaminated water. 4 The diagnosis of AK is a challenging issue. ...
Purpose
To report a rare and complicated case of acanthamoeba keratitis (AK) presented with total necrosis and dislodgment of cornea, iris, and crystalline lens with exposure of vitreous hyaloids face.
Methods
Case report of 28-year-old female referred to the Farabi Eye Hospital with a history of known left eye AK since 4 months earlier. She also had a history of soft contact lens wear for two years and topical steroid use before proper diagnosis. Slit-lamp examination of the left eye revealed ring infiltration and stromal edema with haziness. The patient was prescribed anti-acanthamoeba treatment. She returned after 2 weeks with increasing ring infiltration and slight vision loss. Slit-lamp examination showed spontaneous total necrosis of cornea, iris, and crystalline lens with vitreous exposure to the air.
Results
The patient underwent an urgent operation consisting of total debridement of necrotic tissues including a 1 mm rim of the sclera, anterior vitrectomy, tectonic penetrating keratoplasty, and amniotic membrane transplantation (AMT) with temporary lateral tarsorrhaphy. The graft was clear within the 4 years of follow-up. At the last examination, the left eye was pthysic due to ciliary shut down and visual acuity remained light perception.
Conclusion
Early suspicion to AK, especially in contact lens wearers, and applying diagnostic modalities like confocal microscopy and early appropriate management with cysticide agents such as polyhexamethylene biguanide may prevent these untoward complications.
... The popularity of the contact lens use is rising in Poland; for this reason, severe, vision-threatening AK cases are reported with increasing frequency every year. [4,[13][14][15][16]. The clinical pattern of the disease may include redness, photophobia, excessive tearing, severe eye pain, eyelid edema and progressive visual impairment; epithelial inflammations and hyper reflective tissue of corneal ulcers appearing in affected eyes may be detected by slit-lamp. ...
Amphizoic amoebae belonging to the genus Acanthamoeba are known as etiological agents of sight-threatening Acanthamoeba keratitis. The leading risk factor for the development of this serious human disease is contact lens wearing which popularity increases worldwide, also in Poland. The disease with active epithelial inflammations, corneal ulcers, including loss of the visual acuity is a serious medical problem as an emerging threat for the public health related to improper contact lens hygiene. The treatment of the amoebic keratitis is difficult, often unsuccessful due to delayed proper diagnosis. The clinical picture of the disease, often with severe course is nonspecific, similar to that occurring in viral, fungal or bacterial keratitis, thus clinical symptoms alone are not sufficient to identify the causative agent of the amoebic infection. Early diagnosis is decisive for the suitable therapeutic management and the treatment efficacy. In our studies, several complicated, difficult to treat Acanthamoeba keratitis incidences pertaining Polish patients using contact lenses have been retrospectively analyzed in terms of the usefulness of non-invasive methods of in vivo confocal microscopy and in vitro culture techniques applied for diagnosis. Hyper-reflective double-walled spherical Acanthamoeba cysts, with a more reflective outer wall were detected in the epithelium and anterior layers of the corneal stroma. In vivo confocal microscopy, if available, may be a valuable, sensitive tool for diagnosis in late identified severe infections mainly with strong viability strains, however confoscan may offer limited value at lowintensity amoebic infections. The microscopic visualization of amoebae in slides prepared directly from corneal scraping and laboratory examinations of specimens from in vitro cultivated corneal isolates allow to confirm or verify results of in vivo examinations, furthermore to identify directly the pathogens and to clarify previous misdiagnoses.
... La infección humana por AVL es poco frecuente, sin embargo hay un incremento de casos con la emergencia del VIH/ SIDA en los reportes de MEAP y EGA, ya que los pacientes inmunosuprimidos son particularmente susceptibles a estas infecciones (3,4) . Por otro lado, los casos de KA son más frecuentes por el uso de los lentes de contacto (5) . ...
Objectives. To determine the presence of free-living amoeba (FLA) in water bodies from Lima department and assess their pathogenic ability in normal mice and immunosuppressed. Material and methods. Water samples were collected from rivers, lakes, swimming pools and wells in Lima, Peru. The isolation was performed by culture in non-nutritious agar with 2% of E. coli or E. aerogenes at 37 °C. Subsequently were injected into normal mice and immunosuppressed (betamethasone 1.4 mg/mL, a single dose) with a suspension of amoeba isolated. For the 15 days were assessed histological damage in both groups. Results. AVL were identified in 40/83 samples, 31.3% of the samples were developed in cultures. 26 strains were isolated from AVL of seven genera (Hartmannella, Acanthamoeba, Mayorella, Naegleria, Vahlkampfia, Vannella and Saccamoeba), Acanthamoeba was the most frequent (44.2%). AVL was found in 53.8% of immunosuppressed mice and 15.4% of the normal (p
... Acanthamoeba can cause severe keratitis. Approximately 90% of Acanthamoeba keratitis has been associated with wearing soft contact lenses (SCLs) (Awwad et al. 2007). Most SCL wearers use multipurpose solution (MPS) for disinfecting, rinsing, cleaning, and storing of SCLs. ...
Lactoferrin (LF) is an iron-binding basic glycoprotein that has an antimicrobial effect against certain microbes. The purpose of this study is to evaluate the amoebicidal effect of bovine milk LF (bLF) against Acanthamoeba clinical-isolate trophozoites, which cause severe keratitis. Most of the risk factor for Acanthamoeba keratitis is from wearing soft contact lenses (SCLs). Acanthamoeba trophozoites were incubated in bovine LF (bLF) solution, and the ratios of viability and encystment were determined with microscopic analysis of cyst formation. The amoebicidal effect of bLF was assessed by Trypan blue assay. The ratios of viable cells in the presence of iron-free bLF (apo-bLF), native-bLF, and iron-saturated bLF (Fe-bLF) at the concentration of 10 μmol/L for 60 min were 7.7% ± 4.6%, 80.7% ± 10.1%, and 97.3% ± 1.5%, respectively. Apo-bLF showed potent amoebicidal effect against Acanthamoeba trophozoites, but Fe-bLF did not have this effect. After treating with apo-bLF, most dead cells were nonglobular forms of trophozoites but not cystic forms. Encystment of Acanthamoeba was assessed by the sarkosyl-calcofluor white assay. The encystment ratios treated with 0.5% propylene glycol (positive control) and 10 μmol/L apo-bLF for 24 h were 96.12% ± 10.6% and 0.47% ± 0.5%, respectively. These results suggest that the amoebicidal effect of apo-bLF without encystment might lead to the prevention of contamination of Acanthamoeba in SCL stock cases.
... Therefore, physicians should consider Acanthamoeba keratitis as an alternative diagnosis in patients with presumed herpes simplex keratitis with decreased corneal sensation [159]. Complications of Acanthamoeba keratitis include dacryoadenitis, corneal melting and scarring, severe secondary glaucoma, cataract, and chronic anterior segment inflammation [160]. Progression of the disease led to a cloudy cornea with a stromal ring infiltrate, poor vision, elevated intraocular pressure, mature cataract and finally corneal melt [161]. ...
Purpose:
The US Food and Drug Administration (USFDA) granted the miltefosine orphan drug designation in 2016 for treating Acanthamoeba keratitis. This study evaluates miltefosine's in vitro efficacy against clinical isolates of Acanthamoeba from patients with keratitis and its safety profile in human corneal epithelial cell line to rationalize its localized ocular application.
Methods:
Acanthamoeba spp. isolated from corneal scrapings of keratitis patients (n = 17) were cultured axenically, genotyped, and tested for miltefosine's minimal cysticidal and trophozoicidal concentrations (MCC and MTC) by microbroth dilution method. Safer concentrations of miltefosine were determined using human corneal epithelial (HCE) cells at four incubation points. Trophozoites and cysts of one of the isolates, A. castellanii, were challenged on confluent monolayers of HCE in the presence and absence of miltefosine for 24 h. Cytopathic effects were evaluated using microscopic analysis.
Results:
The majority of Acanthamoeba isolates tested were T4 genotypes (94.11%). MTC90 and MCC90 of miltefosine were 0.125 and 4 mg/mL, respectively. Miltefosine was found safe on HCE at 0.0625 and 0.125 mg/mL for 4 and 0.25 h, respectively. Microscopical findings showed that A. castellanii trophozoites destroyed the cellular structures of HCE within 24 h without miltefosine. Drug pre-treatment prevented the initiation of infection at both the tested concentrations (0.0625 and 0.125 mg/mL) upto 24 h.
Conclusion:
Miltefosine was effective against Acanthamoeba trophozoites and cysts in vitro with >30-fold higher cidal concentration for cysts compared to trophozoites. An effective trophozoicidal concentration of miltefosine (0.125 mg/mL), found to be safe for HCEs, suggests its potential utility as an adjunct treatment for Acanthamoeba keratitis.
Purpose
To investigate the combined anti-Acanthamoeba effects of nitric oxide (NO) donors and hypochlorite to maximize amoebicidal outcomes while minimizing damage to human corneal epithelial cells (HCECs).
Methods
Acanthamoeba castellanii and primary cultured HCECs and keratocytes were treated with sodium hypochlorite (NaOCl), NO donors (sodium nitroprusside [SNP] and sodium nitrite [NaNO2]), or a combination of hypochlorite and NO donors. The viability of A. castellanii, HCECs, and keratocytes was assessed. Minimal inhibitory concentration (MIC) and fractional inhibitory concentration of NaOCl and NO donors were determined. The activation of mammalian targets of rapamycin (mTOR) and ERK and the expression of nitrite reductase and Nrf2 were assessed in HCECs using Western blot analysis. The cysticidal effects of combined NaOCl and NO donors were also evaluated.
Results
A dose-dependent toxicity was observed in A. castellanii, HCECs, and keratocytes when treated with NaOCl and SNP. The range of tested NaNO2 concentrations showed no significant toxicity to HCECs; however, dose-dependent toxicity to A. castellanii was observed. The MIC of NaOCl against HCECs and A. castellanii was 8.0 mg/mL. The MIC of NaNO2 and SNP was 500 mM and 10 mM in both HCECs and A. castellanii, respectively. Weak attenuation of the mTOR and ERK phosphorylation was observed and Nrf2 expression decreased slightly after exposure of HCECs to 2.0 mg/mL NaOCl. For the combination treatment, NaOCl (0.125 mg/mL) was selected based on the safety of HCECs and the toxicity of A. castellanii. A more potent anti-Acanthamoeba effect and HCEC toxicity were observed when NaOCl was combined with SNP rather than NaNO2.
Conclusions
Combined NaOCl and NO donors had a stronger anti-Acanthamoeba effect compared to either drug alone.
Translational Relevance
This study demonstrates that the combined use of various drugs for the treatment of Acanthamoeba infection can enhance the anti-Acanthamoeba effect while minimizing the toxicity of the individual drug.
The Clinical Manual of Contact Lenses , can help both students and practitioners to fit, evaluate, and troubleshoot contact lens issues in everyday practice. Corneal edema occurred significantly more frequently with poly(methyl methacrylate) than with Polycon lenses. Acanthamoeba keratitis is a severe sight‐threatening corneal infection that has become a significant medical problem, especially among contact lens wearers. The disease manifests as eye pain, congestion, blurred vision, lachrymation, and ring‐shaped infiltrates of the cornea, and can lead to permanent blindness. Presbyopia is a condition associated with the aging of the eye that results in progressively worsening ability to focus clearly on close objects. Myopia can be easily corrected with optical and surgical interventions, however, pathological myopia is known to increase the risk of eye diseases such as cataracts, glaucoma and macular degeneration. A disinfecting solution for contact lenses consists of the combination of a polymeric biguanide and a quaternized vinylimidazole polymer.
Acanthamoeba keratitis (AK) is a dangerous disease of the cornea, its prevalence has increased significantly due to widespread usage of contact lenses. The similarity of the clinical manifestations of AK to other infectious keratitis (especially herpetic keratitis) requires introduction of a rapid diagnosis method into clinical practice.
Purpose:
To evaluate the capabilities of corneal confocal microscopy (CCM) in the diagnosis of acanthamoeba keratitis.
Material and methods:
We examined 33 patients (35 eyes) with suspected acanthamoeba keratitis using light and laser confocal microscopy of the cornea (ConfoScan and HRT devices, respectively).
Results:
CCM was technically feasible in 23 of 35 cases (65.7%). Acanthamoeba cysts were detected in 16 cases (69.6%); trophozoites were visualized in 17.4% of cases; signs of keratoneuritis were detected in 12 eyes (52.2%); in 7 cases (30.4%), hyporeflective honeycomb-like cavities were observed in the stroma; deep stromal striae were observed in 9 cases (39.1%); activated keratocytes were detected in 11 patients (47.8%), and Langerhans cells were detected in 19 cases (82.6%).
Conclusions:
The main diagnostic value of confocal microscopy is the detection of direct markers of AK - cysts and trophozoites of Acanthamoeba. Both light and laser CCM techniques are suitable for the diagnosis of AK, but the resolution of laser confocal microscopy is higher. The non-invasive nature of this method and the possibility of multiple subsequent examinations make it possible to verify the diagnosis of acanthamoeba keratitis and monitor the treatment.
Objective
Acanthamoeba keratitis is often refractory to medical and surgical therapy, primarily due to the remarkable resilience of Acanthamoeba cysts. In this study we directly compared the cysticidal activity and potency of several candidate medical therapies in vitro.
Design
Experimental study.
Subjects: in vitro Acanthamoeba specimens obtained from 9 patients with keratitis seen at the Francis I. Proctor Foundation from 2008-2012.
Methods
The minimum cysticidal concentration (MCC) of povidone iodine, natamycin, and chlorhexidine was investigated using an established assay technique. The relative potency of each agent was estimated starting with concentrations commonly used in clinical practice and determining the number of two-fold dilutions required to reach the MCC. Statistical comparisons of relative potency were performed using bootstrap simulations and permutation tests.
Main Outcome Measures
MCC and the number of two-fold dilutions required to reach the MCC.
Results
The MCC for chlorhexidine ranged from 3.1 to 25 μg/mL (median 12.5 μg/mL, interquartile range [IQR] 6.25 to 12.5 μg/mL), for natamycin ranged from 390.6 to 3,125 μg/mL (median 390.6 μg/mL, IQR 390.6 to 781.2 μg/mL), and for povidone iodine ranged from 0.3 to 78.1 μg/mL (median 2.4 μg/mL, IQR 0.6 to 9.8 μg/mL). Doses commonly used in clinical practice (povidone iodine 1%, natamycin 5%, and chlorhexidine 0.04%) were approximately 12, 6, and 5 two-fold dilutions higher than the drug’s corresponding median MCC, respectively (P<0.001 comparing three drugs). Povidone iodine 1% had the highest potency of the three medications tested, requiring more dilutions than natamycin 5% (P<0.001) and chlorhexidine 0.04% (P<0.001) to reach the MCC.
Conclusions
All three medications demonstrated in vitro cysticidal activity in each of the 9 isolates. The potency of 1% povidone iodine was greater than standard formulations of natamycin or chlorhexidine. While its clinical efficacy is yet to be determined, povidone iodine may be considered as a potential adjuvant treatment in cases of recalcitrant Acanthamoeba keratitis.
Clinical signs of Acanthamoeba keratitis are in early stages grey-dirty epithelium, pseudodendritiformic epitheliopathy, perineuritis, multifocal stromal infiltrates, ring infiltrate and in later stages scleritis, iris atrophy, anterior synechiae, secondary glaucoma, mature cataract, and chorioretinitis. Acanthamoeba keratitis is diagnosed by polymerase chain reaction (PCR), confocal microscopy, in vitro culture, and histopathological examination. As conservative treatment, we use up to 1 year triple-topical therapy (polyhexamethylene-biguanide, propamidine-isethionate, neomycin). In therapy-resistant cases, surgical treatment options such as corneal cryotherapy, amniotic membrane transplantation, riboflavin-UVA cross linking, and penetrating keratoplasty are applied.
Purpose
To describe the development and report psychometric properties of the Contact Lens Risk Survey (CLRS) to identify patients at risk for soft contact lens-related complications.
Methods
Psychometric properties of the CLRS, a web-based survey with branching logic, were determined using data from 5 multi-site fieldings (n = 1059), including re-fielding to sub groups. Responses from participants with and without an active red eye were used to identify risk factors of a red eye event and calculate an overall risk score. A 6th fielding of the CLRS (n = 171) was used to assess discriminate validity.
Results
Participants needed 11−12 min to complete the survey with a negligible difference by age. Internal consistency was excellent (Cronbach’s α ≥ 0.70) for 3 of the 5 constructs identified by factor analysis. Twelve of the 17 survey items exhibited excellent within-subject repeatability (Kappa ≥ 0.61). Between-subject agreement, assessed in 18−25 year olds, was high for the majority of items, suggesting good generalizability across different populations of SCL wearers. The ability of the model using individual items of the CLRS to discriminate Controls and participants with a red eye was good with an area under the curve of 0.779.
Conclusion
The CLRS tool is a repeatable and valid instrument to standardize documentation of demographic, behavior, and exposure factors which appear to drive the greatest risk of a contact lens related red eye event.
Context
Acanthamoeba is increasingly implicated in causing keratitis in patients wearing contact lens or ocular trauma and has a poor prognosis. Establishment of an animal model is critical to study the disease pathology, pathogenesis and to evaluate anti-amoebic drugs. Some studies have used contact lenses to establish Acanthamoeba keratitis (AK) in a mouse model, which is expensive and not very successful as lenses get dislodged.
Objective
To assess the feasibility of using parafilm (Bemis Company Inc., USA) as an alternative to contact lens for the establishment of AK in the mouse model.
Methods
Thirty-six Balb/c mice in three groups of six mice each for two strains of Acanthamoeba were used to induce AK. Three experimental approaches used were; i) Acanthamoeba impregnated contact lens, ii) Acanthamoeba impregnated parafilm and iii) scratching followed by inoculation of Acanthamoeba suspension. In all three models, tarsorrhaphy was performed. Infection was evaluated by clinical examination and also through microscopic examination of corneal scrapings and corneal sections.
Results
AK model was successfully established with parafilm whereas only one mouse developed AK with the use of contact lens and none with scratching and Acanthamoeba inoculation.
Conclusion
The use of parafilm is convenient, reliable and cheaper and can be considered an alternative to contact lenses to induce AK in a mouse model.
Microscopic evaluation of the ocular structures has always been a challenge for ophthalmic clinicians and researchers. In Vivo Confocal Microscopy utilized ophthalmologists and scientists to evaluate the anterior segment and revolutionized some aspects of diagnosis and management the patients. Nowadays confocal microscopy is becoming an indispensable tool for studying living cornea and other ocular surface structures at a cellular level. This technology provides fast and non-invasive images of different layers in both normal and pathologic eyes which are so helpful in studying of normal cornea, diagnosis of several disorders and monitoring the patients. The purpose of this chapter is to describe the principles of confocal microscopy and its different types and finally summarize several applications of confocal microscopy and characteristics findings in some of clinical states such as infectious keratitis, dry eye, ocular allergy and contact lens wearing.
Purpose
To summarize actual literature data on clinical signs, differential diagnosis, and treatment of acanthamoeba keratitis.
Methods
Review of literature.
Results
Clinical signs of acanthamoeba keratitis are in early stages grey-dirty epithelium, pseudodendritiformic epitheliopathy, perineuritis, multifocal stromal infiltrates, ring infiltrate and in later stages scleritis, iris atrophy, anterior synechiae, secondary glaucoma, mature cataract, and chorioretinitis. As conservative treatment, we use up to one year triple-topical therapy (polyhexamethylene-biguanide, propamidine-isethionate, neomycin). In therapy resistant cases, surgical treatment options such as corneal cryotherapy, amniotic membrane transplantation, riboflavin-UVA cross-linking, and penetrating keratoplasty are applied.
Conclusion
With early diagnosis and conservative or surgical treatment, acanthamoeba keratitis heals in most cases.
Purpose:
Acanthamoeba keratitis is a well-known intractable corneal infectious disease. We investigated the anti-Acanthamoeba effect of exogenous nitric oxide (NO).
Methods:
Acanthamoeba castellanii was axenically cultured and exposed to various concentrations of NO donors, such as sodium nitrite, sodium nitroprusside (SNP), and NO-releasing silica nanoparticles (coated in branched polyethylene imine, size:100 nm), for 1 to 7 days (sodium nitrite and SNP: 0, 0.1, 1, 10, 100, and 1000 μM; silica nanoparticles: 0, 6.25, 12.5, 25, 50, and 100 μg/mL). Human corneal epithelial cells (HCECs) were cultured and exposed to sodium nitrite, SNP (0, 0.1, 1, 10, 100, and 1000 μM), and silica nanoparticles for 1, 2, and 3 days.
Results:
Sodium nitrite and SNP showed a dose-dependent inhibitory effect on A. castellanii viability. A more prominent inhibitory effect was observed with SNP (less than 10% of organisms survived at 7-day culture with 1000 μM) compared with sodium nitrite. However, more cytotoxicity on HCEC was observed with SNP. NO-releasing silica nanoparticles were successfully internalized into the amoebic cytoplasm and accumulated in large vacuoles. Although blank silica nanoparticles had no inhibitory effect on A. castellanii viability, NO-releasing silica nanoparticles showed a dose-dependent amoebicidal effect. Furthermore, no cystic transformation of A. castellanii was observed under a phase contrast microscope or transmission electron microscope after exogenous NO treatment.
Conclusions:
Our results demonstrated the anti-Acanthamoeba effect of exogenous NO. This finding suggests that NO-releasing drug platforms, including nano-carriers, can be a promising therapeutic strategy for Acanthamoeba keratitis.
This is the protocol for a review and there is no abstract. The objectives are as follows: The objective of this review is to evaluate the effectiveness and safety of medical therapy for the treatment of AK. © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
The present report discusses a new case of dacryoadenitis with extraocular muscle inflammation associated with Acanthamoeba keratitis (AK) in a contact lens wearer. A 41-year-old male, who has worn silicone hydrogel contact lenses on an extended basis for about 10 years, attended with the complaints of vision disturbance, hyperemia, and pain in his right eye. His history revealed that 1.5 month ago, he had been diagnosed with allergic conjunctivitis and had used steroid eye drops. Biomicroscopic examination revealed eyelid edema, chemosis, and ring infiltration, radial keratoneuritis and an epithelial defect in the cornea. Magnetic resonance imaging demonstrated enlarged lacrimal gland with edematous changes consistent with inflammation due to dacryoadenitis. There were also thickening and edema of the right superior oblique and lateral rectus muscle. The treatment protocol for AK was applied with no specific treatment for dacryoadenitis. After 4 months of the treatment, dacryoadenitis and keratitis regressed. Dacryoadenitis and extraocular muscle inflammation may accompany AK more frequently than expected and previously known. The evaluation of the lacrimal gland and extraocular muscles in presence of AK might be beneficial for understanding better the exact clinical picture and course of the keratitis.
Purpose:
To test the ability of responses to the Contact Lens Assessment in Youth (CLAY) Contact Lens Risk Survey (CLRS) to differentiate behaviors among participants with serious and significant (S&S) contact lens-related corneal inflammatory events, those with other events (non-S&S), and healthy controls matched for age, gender, and soft contact lens (SCL) wear frequency.
Methods:
The CLRS was self-administered electronically to SCL wearers presenting for acute clinical care at 11 clinical sites. Each participant completed the CLRS before their examination. The clinician, masked to CLRS responses, submitted a diagnosis for each participant that was used to classify the event as S&S or non-S&S. Multivariate logistic regression analyses were used to compare responses.
Results:
Comparison of responses from 96 participants with S&S, 68 with non-S&S, and 207 controls showed that patients with S&S were more likely (always or fairly often) to report overnight wear versus patients with non-S&S (adjusted odds ratio [aOR], 5.2; 95% confidence interval [CI], 1.4-18.7) and versus controls (aOR, 5.8; CI, 2.2-15.2). Patients with S&S were more likely to purchase SCLs on the internet versus non-S&S (aOR, 4.9; CI, 1.6-15.1) and versus controls (aOR, 2.8; CI, 1.4-5.9). The use of two-week replacement lenses compared with daily disposables was significantly higher among patients with S&S than those with non-S&S (aOR, 4.3; CI, 1.5-12.0). Patients with S&S were less likely to regularly discard leftover solution compared with controls (aOR, 2.5; CI, 1.1-5.6).
Conclusions:
The CLRS is a clinical survey tool that can be used to identify risky behaviors and exposures directly associated with an increased risk of S&S events.
Purposes:
A literature review to describe the current diagnosis and management of Acanthamoeba keratitis.
Results:
Acanthamoeba is a ubiquitous protozoan: 8 species, 5 genotypic classes have been reported to cause keratitis. It is potentially a sight-threatening infection, and there is often a poor prognosis because of a significant delay in diagnosis and frequently a lack of effective medical management. Main risk factors are contact lens wear, poor hygiene, and contact with contaminated water. Current methods of diagnosis include corneal scrapings for histopathologic analysis, tissue culture, confocal microscopy, and polymerase chain reaction (PCR), each are reviewed in turn. Treatment options include medical (biguanides, diamidines, and corticosteroids) and surgical (epithelial debridement, amniotic membrane transplant, and penetrating keratoplasty).
Conclusions:
Earl diagnosis and treatment are required to effectively manage this condition.
A 5-year-old Korean boy developed multiple subcutaneous, nontuberculous granulomas and died with meningoencephalitis. Autopsy disclosed amebic granulomas in subcutaneous tissue, the left adrenal gland, and the pancreas, with more acute inflammatory lesions in the liver, kidney, and brain. The causative organism is believed to be an Acanthamoeba sp.
A model of contact lens-induced Acanthamoeba keratitis was developed in Yucatan micropigs. Pigs fitted with parasite-laden soft contact lenses developed corneal infections that clinically and histopathologically mimicked the human counterpart. Three distinct stages of disease became apparent and were categorized as: acute, condensed infiltrate, and resolution stages. Viable parasites were isolated from corneal scrapings and smears were taken during the acute and condensed infiltrate stages. In addition, cysts could be identified deep within the stroma of histological specimens taken during the resolution stages. The characteristic dense, white ring-like infiltrates, stroma edema, keratic precipitates, and the chronic nature of the infections were similar to those observed in human Acanthamoeba keratitis. Histopathological examination of infected corneas revealed extensive neutrophilic infiltrates, stromal necrosis, and disorganization of the collagen lamellae. The strong correlation between the clinical and histopathologic features of contact lens-induced Acanthamoeba keratitis in the pig as well as the anatomical similarity of the pig eye with the human eye make the porcine model a valuable tool for investigations of the immunology, cell biology, and therapy for Acanthamoeba keratitis.
A crucial requirement for establishing corneal infection by the extracellular protozoal parasite, Acanthamoeba, is the ability of the parasite to bind to the corneal surface. In a series of in vitro studies, we examined the ability of Acanthamoeba castellanii [corrected] to adhere, invade, and damage normal, intact corneas of 11 mammalian and one avian species. A. castellanii [corrected] (80-90% trophozoites and 10-20% cysts) were incubated with corneas for 24 hours in vitro and examined by scanning electron microscopy (SEM). Results of several independent SEM experiments revealed that parasites not only failed to produce cytopathic effects but did not even bind to the corneal epithelium of mice, rats, cotton rats, horses, guinea pigs, cows, chickens, dogs, and rabbits. However, parasites adhered, invaded, and produced severe damage to human, pig, and Chinese hamster corneas during the 24-hour in vitro incubation period. Additional in vitro experiments quantified the binding of A. castellanii [corrected] to the corneas of selected susceptible and nonsusceptible species. In vitro binding assays revealed scant binding of parasites to mouse, rat, and rabbit (range = 5-20 parasites/7.07 mm2 corneal button). In contrast, extensive binding was observed on Chinese hamster, pig, and human corneas (range = 100-200 parasites/7.07 mm2 button). The results indicate that A. castellanii [corrected] exercises rigid host specificity at the host cell surface.
An in vitro coincubation assay was used to measure adhesion of radiolabeled Acanthamoeba trophozoites to corneal epithelium. Adhesion of amebae to corneal epithelium was higher at 25 degrees C than at 37 or 4 degrees C, did not consistently correlate with the reported pathogenicity of the strain of Acanthamoeba, and was inhibited by mannose and by methyl-alpha-D-mannopyranoside.
Following the diagnosis of Acanthamoeba keratitis in a contact lens wearer, the antimicrobial susceptibility of the clinical isolate and the environmental source of the infection were investigated. Contrary to previous reports, in vitro antimicrobial testing showed that the infecting strain was inherently resistant to propamidine isethionate. Restriction endonuclease digestion analysis of Acanthamoeba whole-cell DNA of strains isolated from the patient's cornea, contact lens storage container, saline rinsing solution, and kitchen cold-water tap showed that the isolates were identical. This implicates, for the first time, domestic tap water as the source of Acanthamoeba sp. in this infection. It is therefore recommended that the use of homemade saline solutions and the rinsing of contact lenses in tap water be strongly discouraged.
Axenic cultures of Acanthamoeba castellanii contained a collagenolytic enzyme that digested collagen shields and purified collagen in vitro. Specificity of biologic activity was determined by the addition of selected enzyme inhibitors to the assays and revealed that the parasite-conditioned medium contained both collagenase and lower concentrations of other proteolytic enzymes. However, most of the collagenolytic and pathogenic activity was directly attributable to specific collagenase. Intrastromal injection of sterile, Acanthamoeba-conditioned culture medium into naive Lewis rats produced corneal lesions clinically similar to and closely resembling those found in biopsy specimens of human patients diagnosed with acanthamoebic keratitis. Histopathologic analysis revealed moderate-to-severe neutrophil infiltration, disruption of stromal lamellae, and edema. Identical pathologic sequelae were produced by intrastromal injection of purified collagenase (25 units/ml). The pathogenicity of the soluble parasite-derived product was removed by passage over affinity columns armed with antibody specific for collagenase. These results indicated that soluble parasite-derived factors were capable of producing lesions characteristic of acanthamoebic keratitis and that the pathogenicity of these factors was either directly or indirectly attributable to specific collagenase activity.
Acanthamoeba keratitis is a chronic infection of the human cornea. Many people who have this infection wear soft contact lenses. Usually lens wearers clean and maintain their lenses with various ophthalmic solutions including homemade saline. Recently it has been shown that homemade saline solutions play a role in lens contamination and thus in Acanthamoeba keratitis. We therefore evaluated the viability of cysts of three species of Acanthamoeba by exposing them for various time periods to saline, cleaning, and disinfectant solutions generally used to care for these lenses. We found that the viability of the cysts in saline solutions ranged from a minimum of 14 days to 90 days of exposure. In cleaning solutions, the survival times ranged from a minimum of 1 day to 90 days of exposure. Disinfectants, as expected, were the most effective of all tested solutions in killing Acanthamoeba cysts. The survival times ranged from 6 h to 14 days. None of these products were effective in destroying Acanthamoeba cysts in less than 6 h of exposure, which exceeds the suggested time that any given solution should be used for lens care.
Members of the genus Acanthamoeba are increasingly recognized as agents of indolent, chronic, infectious keratitis. Recently, Acanthamoeba corneal infection has been reported in some persons who wear soft contact lenses. In this study, three "heat" and three "cold" soft contact lens disinfection systems were tested according to the manufacturers' instructions against Acanthamoeba castellanii and Acanthamoeba polyphaga in separate trials, and with appropriate controls. Suspensions of Acanthamoeba cysts or trophozoites of each species were tested individually. Each of the three heat disinfection units killed all acanthamoebae in one cycle in all trials. A chlorhexidine 0.005%/thimerosal 0.001% solution killed A. castellanii trophozoites and cysts, but those of A. polyphaga survived. Trophozoites and cysts of both species survived an alkyl triethanol ammonium chloride 0.013%/thimerosal 0.002% solution and a hydrogen peroxide 3% preparation. Heat disinfection overall appears to be more effective in killing Acanthamoeba trophozoites and cysts as compared to cold disinfection methods.
The first medical cure of a corneal infection due to an Acanthamoeba species is reported. The 44-year-old patient developed a suppurative keratitis associated with an epithelial defect, hypopyon, and secondary glaucoma. Acanthamoeba was confirmed as the causative agent four months after presentation when positive cultures were obtained from the cornea and from the conjunctiva. Sensitivity studies of the isolated organism were performed, and the infection was successfully controlled by treatment with a combination of dibromopropamidine and propamidine isethionate ointment and drops and neomycin drops. Keratoplasty was performed 22 months after onset, and no viable acanthamoebae were present in the resected tissue, though possible cyst remnants were identified by immunofluorescent techniques.
AIM To review the clinical characteristics, diagnosis, and visual outcome in patients with non-contact lens related Acanthamoebakeratitis and compare the findings with reported series of contact lens associated Acanthamoeba keratitis. METHODS Medical and microbiology records of 39 consecutive patients with a diagnosis ofAcanthamoeba keratitis, at a tertiary eyecare centre in India between January 1996 and June 1998, were analysed retrospectively. RESULTS A majority of the patients presented with poor visual acuity and large corneal stromal infiltrates (mean size 38.20 (SD 26.18) mm). A predisposing factor was elicited in 19/39 (48.7%) patients (trauma 15, dirty water splash three, leaf juice one). None of the patients had worn contact lenses. Most patients (26/39 (66.6%)) came from a low socioeconomic background. Complaint of severe pain was not a significant feature and radial keratoneuritis was seen in 1/39 (2.5%) patients. A ring infiltrate was present in 41.1% of cases. A clinical diagnosis of fungal keratitis was made in 45% of the patients before they were seen by us. However, all patients were diagnosed microbiologically at our institute based on demonstration ofAcanthamoeba cysts in corneal scrapings (34/39) and/or culture of Acanthamoeba(34/39). Treatment with biguanides (PHMB, 15/38 (39.4%), PHMB with CHx, 23/38 (60.5%), one patient did not return for treatment) resulted in healing with scar formation in 27 out of 31(87.0%) followed up patients (mean time to healing 106.9 days). Overall visual outcome was poor with no statistical difference between cases diagnosed within 30 days (early) or 30 days after (late) start of symptoms. The visual outcome in cases requiring tissue adhesive (five) and keratoplasty (three) was also poor. CONCLUSIONS This is thought to be the largest series of cases ofAcanthamoeba keratitis in non-contact lens wearers. In such cases, the disease is advanced at presentation in most patients, pathognomonic clinical features are often not seen, disease progression is rapid, and visual outcome is usually poor. Possible existence of Acanthamoeba pathotypes specifically associated with non-contact lens keratitis and unique to certain geographical areas is suggested.
Acanthamoeba is a free-living ubiquitous ameba that is responsible for a small but increasing number of cases of keratitis. The infection is associated with minimal corneal trauma and soft contact lens wear. It typically presents as a unilateral central or paracentral corneal infiltrate, often with a ring-shaped peripheral infiltrate. The lesion is often confused with fungal, bacterial, or herpetic keratitis. Successful therapy hinges on early recognition and aggressive therapy with appropriate topical antiamebic medication, often in conjunction with penetrating keratoplasty. Thirty-five cases from the world literature are reviewed.
Objective:
To identify the methods that result in timely diagnosis and effective treatment of Acanthamoeba keratitis.Methods:
We retrospectively reviewed the medical records of 12 consecutive patients whom we treated for culture-proved Acanthamoeba keratitis in 14 eyes.Results:
Contact lenses were worn in 13 of 14 affected eyes and substandard methods were often used to care for them. The diagnosis was established in all patients by laboratory analysis of corneal scrapings; corneal biopsies were not required. Acanthamoeba organisms were identified on smears from 12 of 14 eyes with use of standard, nonfluorescent stains and recovered in culture from all patients by inoculating scrapings on nonnutrient agar overlaid with Escherichia coli. Eleven of 14 eyes were medically cured with a combination of antiamebic drugs, most commonly propamidine isethionate, neomycin sulfate, and clotrimazole. Topical corticosteroids were used in only one patient. Two of the three eyes that required therapeutic keratoplasty were not treated before surgery according to our usual protocol; the third required keratoplasty for treatment of a severe bacterial superinfection. Twelve of 14 eyes recovered 20/50 or better visual acuity. Bacterial superinfections were a serious problem, with a total of six superinfections occurring in three treated eyes.Conclusion:
With timely diagnosis and medical treatment with a combination of antiamebic drugs and avoidance of topical corticosteroids, most cases of Acanthamoeba keratitis can be cured, with an excellent prognosis for visual recovery.
• Nine cases of Acanthamoeba keratitis not associated with contact lens wear were diagnosed between July 1987 and August 1989. Patients were treated with topical neomycin-polymyxin B-bacitracin (Neosporin) drops alone or in combination with either miconazole nitrate or ketoconazole drops. At the time of data collection four patients were available for follow-up for an average of 4 months; however, four patients were unavailable for follow-up and one is still undergoing treatment. In four patients corneal infiltrates cleared completely with topical medication (Neosporin, two patients; Neosporin plus miconazole, two patients). Simple laboratory methods were found to be adequate for the diagnosis of Acanthamoeba keratitis. Therapy with Neosporin drops can result in resolution of corneal infiltrates due to Acanthamoeba species.
Acanthamoeba keratitis, most frequently occurring in the setting of contact lens wear, has been widely documented over the past several years. We encountered a case of Acanthamoeba keratitis following penetrating keratoplasty without other identifiable risk factors.Report of a Case.
—A 74-year-old white woman underwent penetrating keratoplasty in her right eye for bullous keratopathy. She was referred 6 months later for evaluation of a retrocorneal membrane and glaucoma. Examination revealed a retained Descemet's membrane, stromal edema, epithelial haze, and punctate epithelial erosions in the right eye. Repeated penetrating keratoplasty with extracapsular cataract extraction and posterior chamber intraocular lens was subsequently performed by the referring physician. Three weeks after surgery, the patient developed an inferior stromal keratitis, epithelial defect, and hypopyon in the right eye and was referred for management.See also p 463.Results of anterior chamber and vitreous taps and corneal cultures were negative for organisms, as was subsequent
• Trophozoites and cysts of amebas were found within the necrotic cornea of an enucleated eye. The organism was identified, by indirect immunofluorescent staining using specific antiserum, to be Acanthamoeba castellani. This case report illustrates the difficulty of clinical diagnosis and typical inefficacy of medical therapy shown in other reports of this rare keratitis.
purpose. Acanthamoeba trophozoites express a mannose binding receptor that facilitates adhesion of trophozoites to mannosylated proteins on corneal epithelial cells. This study was undertaken to determine the role that mannose stimulation has in the amoeba’s growth, secreted products, and ability to desquamate the corneal epithelium.
methods. Acanthamoeba castellanii trophozoites were grown in peptone-yeast extract glucose (PYG) and PYG with 100 mM methyl α-d-mannopyranoside or galactose. The proliferation of trophozoites and cysts was examined by optical density and direct counts. The molecular weight of the mannose-stimulated protein was examined by SDS/PAGE. The cytolytic protein was purified by fast protein liquid chromatography (FPLC) size exclusion and ionic exchange and then tested for cytopathic effect (CPE) and collagenolytic activity in vitro. Collagenolytic activity was examined by zymography. Proteases and protease inhibitors were used to characterize the nature of the cytolytic protein.
results. Methyl α-d-mannopyranoside inhibited the growth of A. castellanii by 50% (P < 0.05) and concomitantly induced a threefold increase in the formation of cysts. SDS-PAGE analysis revealed a mannose-induced protein of ∼133 kDa (MIP-133). The MIP-133 protein was found to be highly cytolytic against corneal epithelial cells, but not human intestinal epithelial cells and also degraded collagen in vitro. Serine protease inhibitors abrogated both CPE and collagenolytic activity of the MIP-133 protein (P < 0.001).
conclusions. The results suggest that binding of trophozoites to mannosylated proteins on the corneal surface induces A. castellanii to secrete a ∼133-kDa serine protease that kills both human and hamster corneal epithelium and degrades collagen.
We report 2 cases of cutaneous Acanthamoeba infection in patients with acquired immunodeficiency syndrome. The disease, which manifests as subcutaneous nodules, mimics other more commonly encountered clinical entities. A high index of suspicion, familiarity with the clinical and histologic appearance of skin lesions, and communication between clinicians and pathologists are crucial for early diagnosis and treatment of this potentially fatal infection.
Arch Intern Med. 1997;157:569-572
SYNOPSIS. Ten strains of Acanthamoeba from freshwater habitats were isolated in clonal cultures. Studies were made of trophic structure, nuclear division, cyst structure, some aspects of cytochemistry, and other characteristics. One strain was identified as A. castellanii (Douglas, 1930), one as A. astronyxis (Ray and Hayes, 1954), and 8 as A. polyphaga (Puschkarew, 1913). Strains of Acanthamoeba isolated by other workers were also examined comparatively.
The pattern of nuclear division in all strains resembled that in metazoan cells, with the exception that centrioles were never found. Trophic amoebae had a PAS-positive surface outline. Cyst walls were strongly PAS-positive and also gave a positive test for cellulose with zinc chloroiodide.
The genus Acanthamoeba Volkonsky, 1931 is re-defined, being distinguished from Hartmannella Alexeieff, 1912, emend. Volkonsky, chiefly by the formation of tapering, hyaline pseudopods (acanthopodia) and by a cyst made up of an ectocyst and a polyhedral or stellate endocyst, with excystment by removal of opercula. Other characteristics found in all strains include a distinctive food cup, the presence of many small refractile globules in the cytoplasm of trophic amoebae, and a cyst wall containing cellulose. The degree of spindle convergence, employed by Volkonsky as a generic criterion, was unusable.
Differential diagnoses based principally on cyst structure are offered for A. castellanii, A. astronyxis, and A. polyphaga. The strain previously called Mayorella palestinensis Reich, 1933 is a distinct species of Acanthamoeba.
Purpose. Acanthamoeba keratitis is a sight-threatening corneal infection. It is known that: (i) more amoebae bind to the surface of injured corneas than to the normal corneal surface and (ii) mannose-containing glycoproteins (GPs) possess binding sites for Acanthamoeba. The present study was undertaken to determine whether subtle corneal surface injury exposes mannose-GPs and whether more amoebae bind to the mannose-GPs of injured corneas than to those of normal corneas.
Methods. Corneal cup assays were developed to determine whether corneal surface injury exposes binding sites for a mannose/glucose-specific lectin, succinylated-concanavalin A (s-ConA). To determine whether injury exposes mannose-GPs, corneal surface proteins were biotinylated, biotin-labeled mannose-GPs were allowed to bind to s-ConA-agarose beads and were analyzed by SDS-polyaerylamide gel electrophoresis (PAGE). Amoeba binding to mannose-GPs of corneal epithelia was analyzed by PAGE-blot overlay assays.
Results. S-ConA binding site density was 2.4 times greater on the injured corneal surface than on the surface of normal corneas. Based on the analysis of the s-ConA-bound, biotin-labeled corneal surface proteins, approximately 5.2 times greater amounts of mannose-GPs were present on the surface of injured corneas than on the normal corneal surface. PAGE-blot overlay assays of s-ConA bound GPs of unlabeled corneal epithelia revealed that, on a per mg total cell protein basis, injured corneal epithelium contained 1.8 times greater amounts of Acanthamoeba-reactive mannose-GPs than normal corneal epithelium.
Conclusions. Subtle corneal injury exposes mannose-GPs on the surface of injured corneas. The newly exposed GPs may serve to provide additional attachment sites for the amoebae. This, in turn, could render the cornea susceptible to the infection. Curr. Eye Res. 17:770–776, 1998.
Purpose. A multi-centre survey was conducted to monitor the frequency of Acanthamoeba keratitis (AK), and associated risk factors, during the last 4 years in England. Methods. A consultant in each of the 15 Regional Health Authorities (RHAs) was asked to complete a clinical data sheet for each patient in their region retrospectively identified as presenting with AK between 1. 10. 92 and 30. 9. 96. Clinical and postal patient questionnaire data were entered on to a central database. Results. A preliminary report from 8 RHAs is presented. 213 patients with a diagnosis of AK were identified: 114/213 (55%) were tissue culture / histolog) positive for AK, the remainder having a clinical diagnosis supported by perineural infiltrates (47/99, 47%), or other characteristic features including culture of Acanthamoeba from contact lens (CL) paraphernalia (21/99, 21%). 197213 (92%) patients were CL wearers, and at least 115 (58%) of these were using disposable CL. From CL users who had completed a questionnaire (120) it was possible to identify one or more previously established risk factors - swimming with CL (59), non-sterile water/saline use (14), omitted disinfection (69) and chlorine-based disinfection (49) - in all but 5 patients. The total numbers of patients for each year, excluding those from overseas (14), was 47, 60,64 and 28 respectively, Conclusions. Preliminary results from this survey emphasise the preventable nature of this disease: inadvisable CL practices accounted for i 92/213 (90%) of cases, and it is hypothesised that the reduction in cases during the last year may be the result of improved CL hygiene after widespread media attention to CL-related AK during November 1995.
ABSTRACT The 18S rRNA gene (Rns) phylogeny of Acanthamoeba is being investigated as a basis for improvements in the nomenclature and taxonomy of the genus. We previously analyzed Rns sequences from 18 isolates from morphological groups 2 and 3 and found that they fell into four distinct evolutionary lineages we called sequence types T1-T4. Here, we analyzed sequences from 53 isolates representing 16 species and including 35 new strains. Eight additional lineages (sequence types T5-T12) were identified. Four of the 12 sequence types included strains from more than one nominal species. Thus, sequence types could be equated with species in some cases or with complexes of closely related species in others. The largest complex, sequence type T4, which contained six closely related nominal species, included 24 of 25 keratitis isolates. Rns sequence variation was insufficient for full phylogenetic resolution of branching orders within this complex, but the mixing of species observed at terminal nodes confirmed that traditional classification of isolates has been inconsistent. One solution to this problem would be to equate sequence types and single species. Alternatively, additional molecular information will be required to reliably differentiate species within the complexes. Three sequence types of morphological group 1 species represented the earliest divergence in the history of the genus and, based on their genetic distinctiveness, are candidates for reclassification as one or more novel genera.
PurposeTo characterize patients with Acanthamoeba keratitis and to evaluate the safety and efficacy of propamidine isethionate 0.1% ophthalmic solution (Brolene) when administered concomitantly with neomycin-polymyxin B-gramicidin ophthalmic solution (Neotricin) in the treatment of Acanthamoeba keratitis.DesignProspective, noncomparative case series.MethodsThe authors report the clinical characteristics and outcomes of patients who entered this multicentered, open-label, clinical trial. Eighty-three patients with Acanthamoeba keratitis representing 87 infected eyes entered the trial.ResultsSixty (69%) of the 87 eyes enrolled had data analyzed for treatment efficacy and safety. Of these 60 eyes, 50 (83%) experienced treatment success. Thirty (60%) patients successfully treated adhered to treatment protocol guidelines. Patients who broke protocol had disease exacerbation during the maintenance therapy phase. The only eyes lost/enucleated were 7 of 17 in which penetrating keratoplasty was performed before eradication of the infectious agent.ConclusionPropamidine isethionate and neomycin are an effective treatment for Acanthamoeba keratitis. Penetrating keratoplasty should be performed only for visual rehabilitation and not to “debulk” an active infection. The authors advocate treating patients with topical medications, mainly Brolene, until all organisms are eradicated. There should be no signs of infection for at least 3 months in the patients not receiving antiamebic medications before penetrating keratoplasty is performed.
Trophozoites and cysts of an Acanthamoeba were repeatedly isolated from the corneal scrapings of a patient suffering from acute ulceration of the right eye. The ameba was cloned and cultivated axenically in a proteose peptone-yeast extract-glucose medium. At a later date the organism was identified as A. polyphaga on the basis of its morphologic characteristics, especially those of cysts. Experimental studies on the in vitro interaction of this organism with monkey kidney tissue culture (Vero line) and its pathogenicity to mice indicated that it was a low virulent strain. When large numbers of amebae (25,000+) were inoculated into Vero cell cultures, cytopathic effects (CPE) were noticed within 5 to 6 days. The CPE consisted of cell shrinkage, nuclear pyonosis, and discontinuity of cell sheet, and the cell culture was totally destroyed in 8 to 10 days. When 20,000+ amebae were instilled intranasally into each of 20 2-week-old mice, only 1 mouse died, on the 28th day. Amebae were isolated from the brain of the dead mouse, and trophozoites and cysts were also demonstrated in the brain sections. When amebae isolated from the brain were intranasally instilled into mice, they failed to kill the mice for at least 1 month; however, when 10,000+ amebae were inoculated intracerebrally, the mice died within 5 to 8 days, exhibiting symptoms of primary meningoencephalitis.
Polyhexamethylene biguanide (PHMB) is a polymeric biguanide disinfectant that has not previously been used in the treatment of infection. Six patients with confirmed Acanthamoeba keratitis were treated with PHMB 0.02%. All patients had uncontrolled keratitis refractory to therapy with multiple conventional antiamebic agents. The rationale for use and the dose of PHMB was determined by in vitro sensitivity testing of the Acanthamoeba corneal isolates to the drugs available for use. Trophozoite forms were sensitive to most agents. Only PHMB was cysticidal at low concentrations in all cases. Sensitivity to the other drugs, including propamidine, showed wide variation. In 5 of 6 cases, complete resolution of inflammation followed the introduction of PHMB. Toxicity to the ocular surface was not evident with PHMB, unlike propamidine or neomycin. The reasons for the treatment failure in one case, despite cyst sensitivity to both PHMB and propamidine, are not clear. PHMB is a promising new treatment for this infection.
A 39-year-old man with AIDS died after developing a variety of neurologic symptoms and signs. CT showed multiple enhancing lesions in the cerebral hemispheres and cerebellum. Postmortem examination revealed parenchymal hemorrhagic and necrotizing lesions with a thrombo-occlusive vasculitis due to Acanthamoeba, which was typed as Acanthamoeba group 2, probably A rhysodes, by immunofluorescence.
To the Editor.
—We read the timely article by Sharma and coworkers1 of nine cases of Acanthamoeba keratitis in non-contact lens wearers in India during a 2-year period. We fully agree with the authors that the diagnosis of Acanthamoeba keratitis may be unduly delayed if the clinician fails to consider risk factors other than contact lens wear, ie, foreign-body injuries to the cornea and contact with contaminated water.2 There is very little reason to believe Acanthamoeba keratitis in non-contact lens wearers is a new phenomenon; it is more likely that many of these cases were missed in the past. Only now are we able to appreciate the true incidence of Acanthamoeba keratitis in non-contact lens wearers, owing to a combination of heightened awareness, better clinical diagnostic criteria, and improved laboratory studies.See also p 471.In our own 2-year experience, three of 12 cases of culture-proven Acanthamoeba ulcerative
Radial keratoneuritis, the apparent presence of infiltrate along corneal nerves in suppurative keratitis, has been described1 as an early sign of Acanthamoeba keratitis and is commonly thought to be pathognomonic for this infection. We describe herein a patient with Pseudomonas aeruginosa ulcerative keratitis in which radial keratoneuritis was a presenting sign.Report of a Case.
—A 22-year-old woman who wore extended-wear soft contact lenses first experienced discomfort in her left eye 5 to 7 days before presentation. At that time, she discontinued contact lens wear. Two days before presentation, she noted increasing redness, pain, and photophobia in the left eye. Her ophthalmologist noted radial keratoneuritis, and she was referred to the University of Illinois at Chicago Eye Center for consideration of propamidine isoethinate (Brolene) therapy. On evaluation, she reported 5 years of extended-wear soft contact lens use and had used the current pair for 1 year. Wearing time was
We treated three patients who had Acanthamoeba keratitis with oral itraconazole, a new antifungal agent, topical miconazole, and surgical débridement of the lesion. In these patients, healing and regression of the keratitis began six or seven days after initiation of oral itraconazole and miconazole 0.1% eyedrops (every hour during the day). The clinical signs of corneal infection disappeared after nine weeks in Patient 1, after five weeks in Patient 2, and after eight weeks in Patient 3. Visual acuities improved markedly from hand motions to 20/30 in Patient 1, from counting fingers to 20/16 in Patient 2, and from hand motions to 20/40 in Patient 3. In these patients, no systemic or topical signs of toxicity or adverse reactions were noted during the course of treatment.
Seven patients with documented Acanthamoeba keratitis were treated with prolonged and intensive triple antiamoebic therapy consisting of topical neomycin-polymyxin B-gramicidin, propamidine isethionate 0.1%, and miconazole nitrate 1%. Additionally, five patients were treated with topical corticosteroids. Six of seven patients were cured of Acanthamoeba keratitis with medical therapy alone, one patient required therapeutic penetrating keratoplasty to eradicate the infection. Two patients underwent penetrating keratoplasty to improve their vision after medical therapy. Our series differs from previous reports in that triple antiamoebic therapy was used in all seven patients and was successful in both early and advanced cases of Acanthamoeba keratitis. Prolonged and intensive topical therapy with these three antiamoebic drugs may be an effective mode of therapy for Acanthamoeba keratitis.
An unrecognized case of Acanthamoeba keratitis became quiescent after prolonged scleritis, resulting in a central corneal scar with extensive scleral ectasia. Twenty-one months after the onset of the sclerokeratitis, a penetrating keratoplasty was performed. Acanthamoeba cysts were found in the host corneal button. The corneal transplant has remained thin and clear for 2 1/2 years following surgery. Acanthamoeba keratitis extending to the limbus may become self-limited due to immunologic mechanisms available at the limbus, which do not appear to be active within the cornea itself. However, the prolonged inflammatory reaction manifesting as scleritis may result in extensive scleral ectasia.
Nine cases of Acanthamoeba keratitis not associated with contact lens wear were diagnosed between July 1987 and August 1989. Patients were treated with topical neomycin-polymyxin B-bacitracin (Neosporin) drops alone or in combination with either miconazole nitrate or ketoconazole drops. At the time of data collection four patients were available for follow-up for an average of 4 months; however, four patients were unavailable for follow-up and one is still undergoing treatment. In four patients corneal infiltrates cleared completely with topical medication (Neosporin, two patients; Neosporin plus miconazole, two patients). Simple laboratory methods were found to be adequate for the diagnosis of Acanthamoeba keratitis. Therapy with Neosporin drops can result in resolution of corneal infiltrates due to Acanthamoeba species.
Calcofluor white (CFW) is a chemofluorescent dye with an affinity for the polysaccharide polymers of amebic cysts. Using CFW staining with fluorescent microscopy, we demonstrated amebic cysts in corneal scrapings and keratectomy specimens from four patients with culture-proved Acanthamoeba keratitis and from one in whom CFW was the only positive laboratory test. Calcofluor white staining is simple, rapid, and highly reliable in the diagnosis of Acanthamoeba keratitis.
We examined and treated six patients with acanthamoeba keratitis associated with contact lens wear from 1981 to 1988. Five patients were treated with topical neomycin-polymyxin B-gramicidin (Neosporin) and propamidine isethionate (Brolene) drops. The patients were followed up for an average of 32 months (range 16-75 months). Two patients underwent penetrating keratoplasty at 22 and 26 months after the onset of symptoms and have maintained clear grafts with no evidence of recurrence. In four patients corneal infiltrates cleared on topical medication. All six patients have 6/6 best corrected vision. Early diagnosis and medical treatment alone can result in resolution of corneal infiltrates due to acanthamoebae. With this initial therapy we have had no treatment failures.
We surveyed members of the Ocular Microbiology and Immunology Group and reviewed laboratory requests at the Centers for Disease Control to determine better the epidemiology of Acanthamoeba keratitis in the United States. A total of 208 cases of Acanthamoeba keratitis were identified. The number of cases increased gradually between 1981 and 1984, with a dramatic increase beginning in 1985. Males and females were equally affected. Of the 208 patients, 85 (41%) resided in California, Texas, Florida, or Pennsylvania. Of 189 patients, 160 (85%) wore contact lenses, predominantly daily-wear or extended-wear soft lenses. Of the 138 patients who wore contact lenses and for whom information was available, 88 (64%) used saline prepared by dissolving salt tablets in distilled water. Patients aged 50 years and older were more likely to have had a history of trauma than younger patients, and males were more likely to have a history of trauma than females.
Several diagnostic signs of Acanthamoeba keratitis have been reported recently. We treated three patients who developed a dendritiform epithelial pattern seen early in the course of Acanthamoeba keratitis that likely represents epithelial infection by Acanthamoeba before any stromal involvement. In these three cases, the early diagnosis of Acanthamoeba keratitis coupled with wide epithelial debridement and medical therapy proved effective in eradicating the protozoan. In two additional cases, Acanthamoeba keratitis was not diagnosed until significant stromal involvement was present. Medical therapy was effective in eradicating the organism in one case, although penetrating keratoplasty was necessary for visual rehabilitation. In the other case, medical therapy was ineffective, as corneal perforation resulted and Acanthamoeba cysts were demonstrated by fluorescent staining in the host corneal button.
Two patients with Acanthamoeba keratitis developed a corneal abnormality following prolonged treatment with topical 0.1% [corrected] propamidine isethionate. In both instances, withdrawal of drug therapy resulted in a gradual clearing of the keratopathy, with no permanent sequelae. The changes we observed may be confused with those of active Acanthamoeba infection.
We examined seven patients with Acanthamoeba keratitis. All patients had a history of soft contact lens use. Predisposing factors included use of homemade saline, hydrogen peroxide disinfection, a history of improper lens care, and swimming with contact lenses. Currently recommended medical therapy, including topical propamidine isethionate and dibromopropamidine isethionate, miconazole, Neosporin, corticosteroids, and systemic ketoconazole, was used in all patients. Five patients have undergone penetrating keratoplasty for progressive primary Acanthamoeba keratitis (four patients) or recurrent infection (one patient) after maximal medical therapy. Two patients who began medical therapy less than three weeks after the onset of symptoms have done well. Early diagnosis of Acanthamoeba keratitis appears critical for successful medical therapy. Penetrating keratoplasty continues to have a central role in the management of more advanced cases that are unresponsive, or only transiently responsive, to medical therapy.
Acanthamoeba is a free-living ubiquitous ameba that is responsible for a small but increasing number of cases of keratitis. The infection is associated with minimal corneal trauma and soft contact lens wear. It typically presents as a unilateral central or paracentral corneal infiltrate, often with a ring-shaped peripheral infiltrate. The lesion is often confused with fungal, bacterial, or herpetic keratitis. Successful therapy hinges on early recognition and aggressive therapy with appropriate topical antiamebic medication often in conjunction with penetrating keratoplasty. Thirty-five cases from the world literature are reviewed.
Acanthamoeba is a free-living, fresh-water protozoan that can cause severe corneal disease. Acanthamoeba keratitis can closely mimic epithelial and stromal Herpes simplex keratitis. Three cases of severe keratitis, were referred for treatment. One patient presented with a pseudodendritic epithelial lesion that gradually progressed to stromal involvement. A second patient presented with central stromal infiltrate and necrosis, while a third exhibited features of a disciform lesion with the later development of an immune ring. Acanthamoeba was recovered from the cornea in each case. The distinctive characteristics of the history and clinical findings in Acanthamoeba keratitis can aid the clinician in distinguishing between these two clinical entities. Cytopathology and special staining and culture techniques can confirm the diagnosis.
Three patients (a 13-year-old girl, a 25-year-old man, and a 22-year-old woman) who used daily-wear soft contact lenses, sterilized with saline made from distilled water and salt tablets, developed Acanthamoeba keratitis. Acanthamoeba was cultured from the contact lens solution of one patient. This patient, in whom the diagnosis was made by corneal biopsy early in the clinical course, was successfully treated with topical neomycin-polymyxin, miconazole, and propamidine isethionate. The other two patients underwent penetrating keratoplasty. One of these patients, who received a graft early in the clinical course, developed a recurrence of disease in the graft, whereas the other, who received the graft 18 months after the initial symptoms, has maintained a clear corneal transplant with useful vision.
A healthy Huntingdonshire schoolteacher of 32 had mild unilateral keratoconjunctivitis and uveitis which did not respond to treatment. 6 months later progressive indolent corneal ulceration, pain, and loss of vision led to a corneal graft, which was rejected. A free-living soil amœba, Acanthamœba polyphaga, was repeatedly isolated from the affected eye. A Lincolnshire farmer of 59 developed an identical clinical condition which required enucleation of the eye after a year. A similar Acanthamœba was grown from his eye tissue. These are the first eye infections caused by free-living amœbæ to be reported in the U.K.
A recalcitrant corneal ulcer resulted in an extensive corneal opacity requiring penetrating keratoplasty. Histopathologic studies and subsequent cultures established the diagnosis of Acanthamoeba keratitis. A second transplant was performed due to a culture-proven recurrence of the keratitis in both the recipient and the graft, with progressive thinning. This has remained clear for six months on systemic ketoconazole and topical miconazole drops. This case demonstrates the difficulty in initial diagnosis of Acanthamoeba keratitis and the apparent successful medical control of the infection despite transplantation into an infected recipient bed.
There are 2 main types of meningoencephalitis caused by free-living amoebae. The first is a well-defined acutely fatal disease resembling fulminating bacterial meningitis. It is caused by the single species Naegleria fowleri. The second is a more poorly defined disease that runs a subacute or chronic course and is characterized by focal granulomatous lesions in the brain. The causative organisms are probably Acanthamoeba sp. in most cases, but it is possible that other genera may be involved. The first case of the subacute form of the disease to be recognized in Australia is described. A 2 1/2-yr-old, previously well girl presented with ataxia and lower motor neurone paralyses. The cerebrospinal fluid was pleocytic and she was thought to be suffering from a relatively minor viral brain-stem encephalitis. Her symptoms persisted in a peculiarly fluctuating way for 30 d when she suddenly collapsed and died from an intracranial haemorrhage. Necropsy showed focal granulomatous lesions associated with necrotizing vasculitis in the basal regions of the brain. The lesions contained well preserved free-living amoebae which were morphologically different from N. fowleri and most closely resembled Acanthamoeba sp. The ultrastructure of the organisms was particularly well preserved and is described in some detail. Immunohistological studies also excluded N. fowleri but were inconclusive for Acanthamoeba or other genera of free-living amoebae. Difficulties with the diagnosis and treatment of this disease are discussed and some practical suggestions are made.
The long-term storage of pathogenic and nonpathogenic strains of both Naegleria and Acanthamoeba spp. were tested on Page amoeba saline agar slopes for 24 months at room temperature and for 8 months at -10, 4, 10, and 15 degrees C. Acanthamoeba strains showed better survival potential than Naegleria strains, particularly when they were stored at temperatures equal to or lower than room temperature.
A 67-year-old man with chronic keratitis was treated with a multitude of antibiotics, corticosteroids and other medicines. Despite temporary relief, perforation with iris prolapse occurred about 4 months after the initial symptoms, and the eye had to be removed. Histological examination revealed cystic bodies in the corneal stroma which could be identified as belonging to the genus Acanthamoeba. Trophozoites were seen as well. Although these amoebae are free-living organisms, occurring almost everywhere in the water and air, corneal infections are rare and have been reported only recently. It has been suggested that Acanthamoebae may only invade the tissues in the case of mixed infections or in corneas with a reduced immunological response, e.g. after corticosteroid therapy. Conservative therapy seems to have little effect, although antibiotic/antiviral/antimycotic treatment should supplement antiamoebic therapy, considering the possibility of mixed infections. Penetrating keratoplasty was indicated in most of the reported cases and usually had a beneficial effect.