Acanthamoeba Keratitis Associated with Soft Contact Lenses

Overview of this Dissertation Example

Acanthamoeba Keratitis (AK) is a rare but severe corneal infection caused by free-living Acanthamoeba species, primarily associated with improper soft contact lens hygiene. This infection can lead to vision impairment or blindness if untreated. Acanthamoeba is found in various environmental sources, including water, soil, and air, and improper disinfection of lenses allows the amoeba to infect the eye. Symptoms include eye pain, redness, blurred vision, and tearing. Preventive measures, such as proper contact lens care, are essential to minimize the risk. This literature review dissertation example was written as an example by Best Dissertation Writers.

Literature Review Chapter – Acanthamoeba Keratitis Associated with Soft Contact Lenses

Introduction

Acanthamoeba, which is a free-living amoeba, occurs worldwide in different environments such as water, soil filters of heating, air conditioning units, and ventilation (Johnston et al. 2009). Furthermore, Kilvington et al. (2010) indicate that the microorganism can also be obtained from medical equipment such as dental irrigation units, gastric wash tubing, contact lenses, and contact lens solutions. Other studies, such as Siddiqui, Lakhundi and Khan (2015), Lorenzo-Morales, Khan and Walochnik (2015), and Cope et al. (2016) have discovered that the acanthamoeba presents in vegetables, human, animal tissues, and cell cultures. Furthermore, Johnston et al. (2009) noted that the amoeba is often found in natural and man-made environments, such as dumpsites that are characterised by high levels of herbicides, pesticides, pharmaceuticals, polychlorinated biphenyls and heavy metals, as free-living organism. Kilvington et al. (2010) on the other hand, noted that the Acanthamoeba may reside in the human body as opportunistic disease and often gains entry into the body through the cornea.

The Acanthamoeba keratitis is a very rare disease which is caused by the invasion of the corneal layer of the eye by the Acanthamoeba (Roozbahani et al. 2018). Papaioannou, Miligkos and Papathanassiou (2016) note that approximately between 1.2 million and 3 million people are affected every year around the globe by the disease. Similarly, the study by Antonelli et al. (2018) show that incidences of the disease among the contact lens wearers to be 1 person per 250000 people in the United States of America. Other studies, such as Zimmerman, Nixon and Rueff (2016) and Maycock and Jayaswal (2016) have determined that 3.06 per million contact lens wearers in the Netherlands and between 17.53 and 21.40 per million contact lens wearers in the United Kingdom. Nevertheless, Tabibian, Mazzotta and Hafezi (2016) on the other hand suggest that the incidence of Acanthamoeba keratitis in may be higher in England and Wales than other countries in the United Kingdom as a result of high number of contact lens users. the study by Jiang et al. (2015) about the contact lens users in the United Kingdom discover that between 400 and 800 per 10000 asymptomatic contact lens users experience lens storage cases with Acanthamoeba spp. Nevertheless, the incidence rate of Acanthamoeba keratitis among the assessed population has been determined to the range between 0.01 and 1.49 per 10000 contact lens users. Regardless of the population within which the studies were conducted, it is justifiable to note that the cases of Acanthamoeba keratitis are on the rise. Therefore, there is a need to develop more effective strategies that will help in the management of this disease. As a result of the increasing number of people using contact lens and vulnerable to Acanthamoeba keratitis, there is need to develop strategies for preserving and managing the contact lenses in order to reduce the incidences of Acanthamoeba keratitis.

The Life Cycle of Acanthamoeba

The life cycle of Acanthamoeba is composed of two important stages: the trophozoite and cyst (Moon et al. 2015). According to the information presented in the study by Siddiqui, Lakhundi and Khan (2015), the trophozoite of Acanthamoeba is often flat and irregular in shape and measures between 20 μm and 40 μm. When exposed to favourable environmental conditions, Sifaoui et al. (2018) note that the trophozoite will undergo mitosis process providing it with the ability to phagocytose the food products in such environments. Similarly, Sarnicola et al. (2016) and Roozbahani et al. (2018) claim that the cyst of Acanthamoeba keratitis develops following the exposure of trophozoite to adverse environmental conditions, such as starvation, hyperosmolarity, elevated temperatures, and exposure to biocidal agents. Effective understanding of the stimuli that influence the occurrence of encystations among the Acanthamoeba will help in the formulation of strategies for a successful interpretation of the life cycle of the parasite and hence prevent the recurrent of the infections caused by this microorganism. In most cases, Acanthamoeba cysts develop high resistance to biocidal agents, hence providing them with the ability to survive in a harsh condition. While supporting the ability of Acanthamoeba to survive in adverse conditions, Johnston et al. (2009) state that the cysts also persists into the stroma during the treatment process with biocidal agents, and that they would also excyst after the conditions turn favourable. As earlier noted, exposing the trophozoite to adverse environmental conditions would influence the development of cyst, as a protective mechanism. As cited in the study by Sifaoui et al. (2018), both the trophozoites and cysts often gain entry into the body through different means, such as the eye, the nasal passages found in the respiratory tract, ulcered, or broken skin among others. Specifically, when the Acanthamoeba spp. gains entry into the body through the eye, it influences the manifestation of severe keratitis, in otherwise healthy individuals, particularly among the contact lens users.

The developed cysts make the eradication of amoeba from the host cells to be difficult (Kilvington et al. 2010). The cysts always present a lot of challenges during treatment, and that it why Sifaoui et al. (2018) noted that the trophozoite is the diagnostic stage of Acanthamoeba. The severity of Acanthamoeba keratitis often depends on the Acanthamoeba attachment and invasion of the corneal cells. Even though Battaini et al. (2018) state that the mannose-binding protein (MBP) is actively involved in the encystment of Acanthamoeba, Siddiqui, Aqeel and Khan (2016) on the other hand argue that the exact role played by the protein during the cyst development process is still not known. While explaining the influence of MBP in the cyst development, Battaini et al. (2018) note that the process is associated with the down-regulation of MBP as well as with the inability of the encysted parasite to successfully bind to the host cells and produce in vitro potent cytopathic effect (CPE).

Jiang et al. (2015) successfully sequence the steps involved in the encystment process of the Entamoeba, a different parasite that is actively involved in the production of infections in the gut. Regarding their findings, following the deprivation of nutrients and the exposure to the hypo-osmotic stress, the trophozoites would aggregate and then undergo encystment process. Fortunately, the aggregation process was stopped by adding free galactose that prevented the successful completion of the encystment process. For that matter, the findings are in agreement with those from the research study by Sarnicola et al. (2016), which state that free galactose inhibited the cyst development in some of the Acanthamoeba spp.

Sources of Infection and Risk Factors for Acanthamoeba keratitis

According to Brown et al. (2018), the Acanthamoeba keratitis is often associated with a soft contact lens. Similarly, Fasciani et al. (2019) highlight that the Acanthamoeba is, in most cases, introduced to the eye through contact lenses that have been endangered by the microorganism following the long use of contaminated lens solutions. While supporting the impacts of lens contamination on Acanthamoeba keratitis infection, Siddiqui, Aqeel and Khan (2016) and Kilvington et al. (2010) identify homemade saline-based solutions and tap water as some of the most important sources of contaminations that influence the occurrence of this microbial infection. Based on the arguments presented in the study by Atkins (2011), bathing or swimming while wearing contact lenses are other important risk factors that are associated with the Acanthamoeba keratitis infection.

Even though most of the studies, such as Zimmerman, Nixon and Rueff (2016) and Johnson, Murphy and Boulton (2006), focus on the impacts of contaminated solutions on the Acanthamoeba keratitis infection risks, Hsia et al. (2018), on the other hand, determine that the infections might also be put into the eye following the exposure to vegetation, soil or by trauma. Hsia et al. (2018) specifically note that the first case of Acanthamoeba keratitis infection was developed following exposure to ocular trauma. After gaining entry into the contact lens, Acanthamoeba can survive within the space between the contact lens and the surface of the eye (Atkins 2011). As soft contact lenses are highly adherent to the surface of the cornea as compared to the hard lenses, the Acanthamoeba will be more likely to bind to the mannosylated glycoproteins found on the corneal surface of the soft lens users (Neelam and Niederkorn 2017). Therefore, the mannosylated glycoprotein expression on the corneal surface depends on the increased use of contact lenses.

Atkins (2011) also indicates that contact lens use can increase the content of glycoproteins, together with the microtrauma, in the corneal epithelial surface, increasing the risk for infection. After the Acanthamoeba has successfully gained entry into the eye surface, it will invade the epithelium and the Bowman’s layer of the eye.

During the progression process of the disease, the Acanthamoeba might also penetrate through the cornea, with little infections inside the eye (Ortillés et al. 2017). Severe infection inside the eye is often prevented as a result of the strong occurrence of neutrophil response within the anterior chamber. Even though Maycock and Jayaswal (2016) and Moon et al. (2015) note that the vast majority of the contact lens wearers are the ones affected by Acanthamoeba keratitis infection, the study by Cope et al. (2016) add that even the non-contact lens wearers are also at risk of being affected by this infection. This study determines that exposure to trauma and the use of contaminated water are the most important risk factors for the development of Acanthamoeba keratitis infections among the non-contact lens wearers. Furthermore, other types of predisposing factors that can increase the chances of an individual to develop Acanthamoeba keratitis infection include contaminated home water supply as well as socioeconomic status. In a different study by Tabibian, Mazzotta and Hafezi (2016), people living in tropical and sub-tropical climates appear to be at high risk of being infected by Acanthamoeba keratitis. In addition to the inoculation route into the eye as well as the external risk factors, Cristian et al. (2019) notice that host factors, such as such as tear film composition, pH value of the eye surface, corneal epithelial defects, as well as the level of anti-Acanthamoeba immunoglobulin-A (IgA) antibodies within the tear film, also significantly contribute to the development of Acanthamoeba keratitis infections.

Acanthamoeba keratitis diagnosis

As a result of the relative rarity of Acanthamoeba keratitis as compared to other potential causes of keratitis, such as viral or bacterial infection of the eye, this infection is often misdiagnosed (Kusrini et al. 2016). Correspondingly, Carnt and Stapleton (2016) agree that there are increasing cases of Acanthamoeba keratitis misdiagnosis, especially in the early stages of disease development. After the occurrence of corneal abrasion or trauma, it is often recommendable for the medical health practitioners to consider Acanthamoeba keratitis diagnosis, especially among those using contact lenses. Even though Padzik et al. (2016) offer that all contact lens users with corneal infections should be diagnosed with Acanthamoeba keratitis. Sharma, Joseph and Pasricha (2018) and Brown et al. (2018), on the other hand, call for the need to get a thorough history, especially regarding the contact lens use and any recent changes in the contact lens solutions. 

Moreover, exposure to water and foreign objects are other factors that Sticca et al. (2018) recommend for a thorough assessment. Different studies have assessed and determined various symptoms which are classically associated with the Acanthamoeba keratitis infection. For example, Sifaoui et al. (2018) highlight blurred or decreased vision whereas Jofré et al. (2018) and Raghavan et al. (2019) identify increased sensitivity to light (photophobia) and redness of the eye (conjunctival hyperemia) as other important symptoms for Acanthamoeba keratitis infections. Besides, the appearance of the pain out of proportion to the physical examination outcomes is explained in the study by (Lin et al. 2016). The findings obtained during the physical examination largely depend on the developmental stage of the disease.

During the early manifestation of Acanthamoeba keratitis in the cornea, pseudo-dendrites, punctate keratopathy, and subepithelial or epithelial corneal deposits might be observed (Roozbahani et al. 2019). The occurrence of these futures may affect that the medical practitioner examining the patient confuses Acanthamoeba keratitis with the viral keratitis, as in the case of those developed after the infection by Herpes zoster virus or Herpes Simplex virus (Padzik et al. 2016). In this regard, the information presented in this study agrees with those from the study by Carnt and Stapleton (2016) that indicates that both the Acanthamoeba keratitis and keratitis caused by viral infections have some similarities in their symptoms. Following the progression and infiltration of the Acanthamoeba keratitis infection in the corneal stroma, Sharma, Joseph and Pasricha (2018) note that there may be the development of a classic ring infiltrate. 

Even though Koltas et al. (2015) also report the development of this ring, and their study shows that only 50 per cent of the examined patients have this kind of ring. As cited in the study by Ortillés et al. (2017), the corneal ulceration and perforation, accompanied by hypopyon, might also be observed. In most cases, the diagnosis of Acanthamoeba keratitis is typically confirmed after the assessment of the corneal scrapings (Roozbahani et al. 2019). The scrapings are always obtained from the cornea and the plated-on agar for culturing purposes. Differentiating between Acanthamoeba keratitis and bacterial keratitis might be very difficult (Sticca et al. 2018). So, the developed culture would then be stained through the application of Giemsa stain or Gram stain. Sifaoui et al. (2018) note that the Acanthamoeba keratitis infection will group around the corneal nerves, after entering the eye surface, leading to the production of radial deposits known as radial keratoneuritis and cause severe pain in the eyes of the affected individuals. Similar features often emerge among patients affected by both viral and bacterial keratitis that might be misleading during the diagnosis and treatment process (Kam et al. 2017). Papaioannou, Miligkos and Papathanassiou (2016) further explain that the Acanthamoeba also can successfully invade deeply into the corneal layer and the stroma of the cornea through the use of metalloproteases.

In order to culture the Acanthamoeba cells successfully, the obtained scrapings should be placed on a non-nutrient agar saline plate, which is then seeded with a gram-negative bacterium, for example, Escherichia coli. In a situation where the Acanthamoeba spp. is present, they easily reproduce increasing their visibility on the plate under the 10-20X objective lens on an inverted microscope (Solanki et al. 2015). Siddiqui, Lakhundi and Khan (2015) also notice that the confirmation of the Acanthamoeba keratitis may be reached through the use of polymerase chain reaction (PCR), especially in a situation where the contact lenses are not involved. Besides, Lin et al. (2016) add that the application of confocal microscopy, which is a non-invasive technique, might influence the successful visualisation of the Acanthamoeba spp. in vivo, especially in a situation where culture, corneal scraping, and cytology do not produce results that may be used for diagnosis.

Management Strategies for Acanthamoeba Keratitis Infection

Even though different classes of drugs exist, such as anti-protozoa, anti-fungal and anti-neoplastic agents, Nunes et al. (2016) argue that there is still no single therapy which can successfully eliminate both the trophozoite and cystic forms of the Acanthamoeba as well as facilitate the eradication of corneal infections. According to the information provided by Koltas et al. (2015), polyhexamethylene biguanide (PHMB) is the most common drug used in the management of Acanthamoeba keratitis, as a result of its effectiveness, with approximately between 0.02% and 0.06% drops are required. Even though Jofré et al. (2018) also support the use of PHMB, the application of between 0.02% and 0.20% of chlorhexidine was also determined to have the ability to manage the Acanthamoeba keratitis infections, but not as a long-term management approach. Both of these drugs affect the Acanthamoeba by disrupting its trophozoite cell wall preventing it from developing to a cyst which is very difficult to manage. Furthermore, both the drugs are appropriate in terms of effectiveness and efficacy during the management of Acanthamoeba keratitis.

Based on the findings from the study by Raghavan et al. (2019), it is justifiable to note that the PHMB might show a higher level of effectiveness against the Acanthamoeba when it is used in combination with other groups of medications such as diamidines, propamidine isethionate, and the hexamidine. Nevertheless, Johnson, Murphy and Boulton (2006) do not fully recommend the use of diamidines on patients with Acanthamoeba keratitis as the drug might cause corneal toxicity after long-term use. The treatment process is often initiated by topical administration of drops of sodium hyaluronate onto the eye surface after hour, 24 hours a day (Solanki et al. 2015). Besides the anti-amoebic therapies, Johnson, Murphy and Boulton (2006) indicate that topical steroids of anti-inflammatory medications are also effective medication approach for Acanthamoeba keratitis management. The main aim of topical steroids is to decrease or eliminate inflammation caused by the infection to alleviate the symptoms. Besides, when there is a severe infection of the cornea, surgical treatment may be recommended (Nunes et al. 2016). For example, the keratoplasty might be recommended in cases of corneal ulceration or perforation.

Solutions for Managing Contact Lenses

Lens care solutions are products that are used for cleaning, disinfecting and storing the lenses in order to protect them from contamination (Roozbahani et al. 2019). Raghavan et al. (2019) added that proper contact lens care is very essential for keeping the contact lens users’ eyes healthy and free from infections. Hydrogen peroxide-based solutions have been in the recent years used for managing contact lenses. According to the information provided in the study by Maycock and Jayaswal (2016) and Moon et al. (2015), Clear Care, which is one of the most important hydrogen peroxide-based contact lens care solution, has the ability of preventing the development of both amoebic and bacterial biofilms that form on the contact lens which might lead to information. In that study, it was noted that the Clear Care led to 6 logs and 5.07 logs reduction of Acanthamoeba and S. aureus biofilms respectively. For that matter, this solution is very important when caring for the contact lenses. In another study by Sarnicola et al. (2016), the effectiveness and efficacy of multipurpose solutions, such as ReNu Multiplus and ReNu with Moisture Loc, Complete MoisturePlus and AQuify were tested against the Acanthamoeba and the bacterial based biofilms, such as Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus aureus. The results from that study determined that the multipurpose were effective on eliminating the bacterial biofilms. Unfortunately, they were not effective in preventing contact lens contamination caused by Acanthamoeba. An important factor that has made such solutions to be less effective and show low efficacy on Acanthamoeba is their inability to induce cyst formation.

Gaps in Literature and Future Research Areas

The management of Acanthamoeba keratitis has been determined by different research studies, such as Kusrini et al. (2016), Fasciani et al. (2019) and Kam et al. (2017), to be unsuccessful after the Acanthamoeba develops into a cyst form. Most studies, therefore, focus on the management of this infection while the Acanthamoeba is still in its trophozoite stage of development. There is a need to conduct future research studies that will help in formulating therapeutic strategies used in the management of Acanthamoeba keratitis infections especially when Acanthamoeba have developed to cyst form. Cristian et al. (2019) report that despite different host factors, such as tear film composition, pH value of the eye surface, and the level of anti-Acanthamoeba IgA antibodies to increase the chances of an individual developing Acanthamoeba keratitis, the actual mechanism of action for these factors has not been successfully determined. Therefore, this is another important area for future research in this field. Another important research gap is derived from the findings presented by Neelam and Niederkorn (2017) which show that soft contact lenses are highly adherent to the corneal surface as compared to the hard ones. Therefore, future research studies should be conducted in this area to define the most appropriate class of contact lenses for those diagnosed with Acanthamoeba keratitis. Large percentage of the solutions that have been developed for managing the contact lens are less effective on the contaminations caused by Acanthamoeba. For that matter, there is need to conduct research study on this area in order to formulate the most effective contact lens solution that may prevent the occurrence of Acanthamoeba contamination.

Chapter Summary

The number of people affected by Acanthamoeba keratitis has been increasing in recent years despite the availability of therapeutic approaches that can be used for handling infections. Some of the key risk factors that influence the appearance of Acanthamoeba keratitis infections include long-term wearing of contact lenses, corneal trauma, and exposure to contaminated water. Additionally, low-levels of anti-acanthamoeba IgA in the tears is also another important risk factor. Managing Acanthamoeba keratitis is very difficult, especially when the Acanthamoeba has developed to its cyst form. In this regard, early diagnosis is always recommended while still in its trophozoite form. Even though there are a lot of studies which have assessed Acanthamoeba keratitis and its management, there are still some important gaps in the literature that should be filled. The gaps comprise the development of therapeutic strategies for managing cyst form of Acanthamoeba, determining the most appropriate lens for Acanthamoeba keratitis patients, and assessing the impacts of host factors in the occurrence of Acanthamoeba keratitis infections.

References

• Antonelli, A., Favuzza, E., Galano, A., Montalbano, D.F.M., Ciccone, N., Berrilli, F., Mencucci, R., Di Cave, D. and Rossolini, G.M., 2018. Regional spread of contact lens-related Acanthamoeba keratitis in Italy. The new microbiological, 41(1), pp. 83-85.
• Atkins, N. 2011. Contact lens care – Latest developments, pp.18-23.
• Battaini, A., La Scola, B., Yin, G.H.W., Hoffart, L. and Drancourt, M., 2018. Amebaborne “Attilina massiliensis” Keratitis. Emerging infectious diseases, 24(2), pp. 387-395.
• Brown, A.C., Ross, J., Jones, D.B., Collier, S.A., Ayers, T.L., Hoekstra, R.M., Backensen, B., Roy, S.L., Beach, M.J., Yoder, J.S. and Acanthamoeba Keratitis Investigation Team, 2018. Risk Factors for Acanthamoeba Keratitis—A Multistate Case-Control Study, 2008–2011. Eye & contact lens, 44, pp. S173-S178.
• Carnt, N. and Stapleton, F., 2016. Strategies for the prevention of contact lens‐related Acanthamoeba keratitis: a review. Ophthalmic and physiological optics, 36(2), pp. 77-92.
• Cope, J.R., Collier, S.A., Schein, O.D., Brown, A.C., Verani, J.R., Gallen, R., Beach, M.J. and Yoder, J.S., 2016. Acanthamoeba keratitis among rigid gas permeable contact lens wearers in the United States, 2005 through 2011. Ophthalmology, 123(7), pp. 1435-1441.
• Cristian, C., Marco, C.D.V., Arturo, K., Claudio, P., Miguel, S., Rolf, R., Remigio, L. and Leonidas, T., 2019. Accelerated collagen cross-linking in the management of advanced Acanthamoeba keratitis. Arquivos brasileiros de oftalmologia, (AHEAD).
• Fasciani, R., Brocca, D., Agresta, A., Grimaldi, G. and Caporossi, A., 2019. Acanthamoeba Ocular Infection: Anomalous Presentation of a Potentially Vision-Threatening Condition. SN Comprehensive Clinical Medicine, 1(2), pp. 113-117.
• Hsia, Y.C., Moe, C.A., Lietman, T.M., Keenan, J.D. and Rose-Nussbaumer, J., 2018. Expert practice patterns and opinions on corneal cross-linking for infectious keratitis. BMJ open ophthalmology, 3(1), pp. 24-31.
• Jiang, C., Sun, X., Wang, Z. and Zhang, Y., 2015. Acanthamoeba keratitis: clinical characteristics and management. The ocular surface, 13(2), pp. 164-168.
• Jofré, A., Avila, F., Aznar, M., Martínez, J.E., Martos, A., Gonzalez, D., Morales, J.A., Acosta, P.J., Urda, J. and Castro, M.A., 2018. 5PSQ-094 Efficacy and duration in treatment of acanthamoeba keratitis. prevalence and risk factor of the infection.
• Johnson, M.E., Murphy, P.J. and Boulton, M., 2006. Effectiveness of sodium hyaluronate eyedrops in the treatment of the dry eye. Graefe’s Archive for Clinical and Experimental Ophthalmology, 244(1), pp. 109-112.
• Johnston, S.P., Sriram, R., Qvarnstrom, Y., Roy, S., Verani, J., Yoder, J., Lorick, S., Roberts, J., Beach, M.J. and Visvesvara, G., 2009. The resistance of Acanthamoeba cysts to disinfection in multiple contact lens solutions. Journal of clinical microbiology, 47(7), pp.2040-2045.
• Kam, K.W., Yung, W., Li, G.K.H., Chen, L.J. and Young, A.L., 2017. Infectious keratitis and orthokeratology lens use: a systematic review. Infection, 45(6), pp. 727-735.
• Kilvington, S., Huang, L., Kao, E. and Powell, C.H., 2010. Development of a new contact lens multipurpose solution: Comparative analysis of microbiological, biological and clinical performance. Journal of Optometry, 3(3), pp. 134-142.
• Koltas, I.S., Eroglu, F., Erdem, E., Yagmur, M. and Tanır, F., 2015. The role of domestic tap water on Acanthamoeba keratitis in non-contact lens wearers and validation of laboratory methods. Parasitology research, 114(9), pp. 3283-3289.
• Kusrini, E., Hashim, F., Azmi, W.N.N.W.N., Amin, N.M. and Estuningtyas, A., 2016. A novel antiamoebic agent against Acanthamoeba sp.—A causative agent for eye keratitis infection. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 153, pp. 714-721.
• Lin, L., Kim, J., Chen, H., Kowalski, R. and Nizet, V., 2016. Component analysis of multipurpose contact lens solutions to enhance activity against Pseudomonas aeruginosa and Staphylococcus aureus. Antimicrobial agents and chemotherapy, 60(7), pp. 4259-4263.
• Lorenzo-Morales, J., Khan, N.A. and Walochnik, J., 2015. An update on Acanthamoeba keratitis: diagnosis, pathogenesis and treatment. Parasite, 22(3), pp. 34-41.
• Maycock, N.J. and Jayaswal, R., 2016. Update on Acanthamoeba keratitis: diagnosis, treatment, and outcomes. Cornea, 35(5), pp. 713-720.
• Moon, E.K., Kim, S.H., Hong, Y., Chung, D.I., Goo, Y.K. and Kong, H.H., 2015. Autophagy inhibitors as a potential antiamoebic treatment for Acanthamoeba keratitis. Antimicrobial agents and chemotherapy, 59(7), pp. 4020-4025.
• Neelam, S. and Niederkorn, J.Y., 2017. Focus: infectious diseases: pathobiology and immunobiology of Acanthamoeba keratitis: insights from animal models. The Yale journal of biology and medicine, 90(2), pp. 261-268.
• Nunes, T.E.T., Brazil, N.T., Fuentefria, A.M. and Rott, M.B., 2016. Acanthamoeba and Fusarium interactions: A possible problem in keratitis. Acta Tropica, 157, pp. 102-107.
• Ortillés, Á., Goni, P., Rubio, E., Sierra, M., Gámez, E., Fernández, M.T., Benito, M., Cristóbal, J.Á. and Calvo, B., 2017. A rabbit model of Acanthamoeba keratitis: Use of infected soft contact lenses after corneal epithelium debridement with a diamond burr. Investigative ophthalmology & visual science, 58(2), pp. 1218-1227.
• Padzik, M., Starosciak, B., Szaflik, J.P., Pietruczuk-Padzik, A., Siczek, P. and Chomicz, L., 2016. Assessment of in vitro dynamics of pathogenic Acanthamoeba strains originating from contact lens wearers with infectious keratitis. Annals of parasitology, 62(4), pp. 33-41.
• Papaioannou, L., Miligkos, M. and Papathanassiou, M., 2016. Corneal collagen cross-linking for infectious keratitis: a systematic review and meta-analysis. Cornea, 35(1), pp. 62-71.
• Raghavan, A., Baidwal, S., Venkatapathy, N. and Rammohan, R., 2019. The Acanthamoeba–Fungal Keratitis Study. American journal of ophthalmology, 201, pp. 31-36.
• Roozbahani, M., Hammersmith, K.M., Rapuano, C.J., Nagra, P.K. and Siu, S.Y., 2018. Acanthamoeba Keratitis: Are Recent Cases More Severe? Cornea, 37(11), pp. 1381-1387.
• Roozbahani, M., Hammersmith, K.M., Rapuano, C.J., Nagra, P.K. and Zhang, Q., 2019. Therapeutic penetrating keratoplasty for acanthamoeba keratitis: a review of cases, complications and predictive factors. International Ophthalmology, pp. 1-8.
• Sarnicola, E., Sarnicola, C., Sabatino, F., Tosi, G.M., Perri, P. and Sarnicola, V., 2016. Early deep anterior lamellar keratoplasty (DALK) for Acanthamoeba keratitis poorly responsive to medical treatment. Cornea, 35(1), pp. 1-5.
• Sharma, S., Joseph, J. and Pasricha, G., 2018. Acanthamoeba Keratitis—Pathogenesis and Diagnosis. Gems of Ophthalmology: Cornea & Sclera, pp. 202-209.
• Siddiqui, R., Aqeel, Y. and Khan, N.A., 2016. The development of drugs against Acanthamoeba infections. Antimicrobial agents and chemotherapy, 60(11), pp. 6441-6450.
• Siddiqui, R., Lakhundi, S. and Khan, N.A., 2015. Status of the effectiveness of contact lens solutions against keratitis-causing pathogens. Contact Lens and Anterior Eye, 38(1), pp. 34-38.
• Sifaoui, I., Reyes-Batlle, M., López-Arencibia, A., Chiboub, O., Rodríguez-Martín, J., Rocha-Cabrera, P., Valladares, B., Piñero, J.E. and Lorenzo-Morales, J., 2018. Toxic effects of selected proprietary dry eye drop on Acanthamoeba. Scientific reports, 8(1), pp. 1-9.
• Solanki, S., Rathi, M., Khanduja, S., Dhull, C.S., Sachdeva, S. and Phogat, J., 2015. Recent trends: Medical management of infectious keratitis. Oman journal of ophthalmology, 8(2), pp. 83-91.
• Sticca, M.P., Carrijo-Carvalho, L.C., Silva, I.M., Vieira, L.A., Souza, L.B., Junior, R.B., Carvalho, F.R.S. and Freitas, D., 2018. Acanthamoeba keratitis in patients wearing scleral contact lenses. Contact Lens and Anterior Eye, 41(3), pp. 307-310.
• Tabibian, D., Mazzotta, C. and Hafezi, F., 2016. PACK-CXL: corneal cross-linking in infectious keratitis. Eye and Vision, 3(1), pp. 11-19.
• Zimmerman, A.B., Nixon, A.D. and Rueff, E.M., 2016. Contact lens associated microbial keratitis: practical considerations for the optometrist. Clinical optometry, 8(3), pp. 1-9.