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Advances in Ocular Surface Infections

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A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 27730

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Dr. Nicole Carnt

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Guest Editor

School of Optometry and Vision Science, University of New South Wales, Sydney, NSW, Australia
Interests: optometry; vision; ophthalmology; biological markers

Prof. Dr. Fiona Stapleton

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Guest Editor

School of Optometry and Vision Science, University of New South Wales, Sydney, NSW, Australia
Interests: contact lenses; ocular surface; dry eye; ocular microbiology; corneal infection
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Eric Pearlman

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Guest Editor

Department of Physiology and Biophysics, University of California, Irvine, CA, USA
Interests: innate immunity; bacterial infections; fungal infections; neutrophils; keratitis

Dr. Connie Tam

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Guest Editor

Department of Ophthalmology, Cleveland Clinic Foundation, Cleveland, OH, USA
Interests: epithelial biology; bacterial keratitis

Special Issue Information

Dear Colleagues,

Advances in ocular surface infections are needed across three domains: 1. epidemiology/prevention/prophylaxis; 2. diagnosis; 3. management.

The risk factors for ocular surface infections in developed countries are led by contact lenses and trauma in working-aged adults, and by surgical or other trauma and ocular-surface quality in older ages. In developing countries, trauma is the key risk factor. Novel ways to impart knowledge of risk factors and change behaviour are urgently needed, as contact lenses are marketed to more of our population, including young children (as myopia control), and environmental organisms are being altered with the effects of climate change and pollution on the microcosm. Several studies have shown complex genomic associations with susceptibility to ocular surface infection, which is an emerging field.

Infections of the ocular surface are in most cases difficult to diagnose clinically, relying on laboratory culture as a gold standard diagnosis, which returns a positive result in only around 50% of presumed cases. PCR is unable to determine active compared to quiescent infection. In practice, the use of ocular imaging for the posterior eye has grown exponentially over the past 10 years, but in the ocular surface, imaging advances are mainly confined to the research domain.

Most ocular surface infections are due to bacteria, and are treated successfully with antibiotics. However, the increase in global antibiotic resistance is challenging this paradigm, and alternative agents for treatment are urgently required. Fungal pathogens are more common causes of corneal infection in rural or tropical areas, and while rare, disease caused by other environmental pathogens such as Acanthamoeba results in a more severe outcome. The treatment options for these infections are more limited, and require attention. Herpesvirus ocular surface infections are also fraught with resistance to treatment. SARS-CoV-2 has been found in the tears of patients, and the cornea and conjunctiva both harbour the ACE2 receptors for the spike protein of the virus. Ophthalmic practice is familiar with epidemic adenovirus keratoconjunctivitis, which can cause the shutdown of services, so the cognizance of emerging viruses is crucial.

For the cornea, limiting damage due to scarring and uncontrolled inflammation is crucial, due to the requirement of highly organised transparent tissue and the barrier to internal eye infection, which can rapidly lead to loss of the eye. Currently, glucocorticosteroids and matrix metalloproteinases are administered as blunt tools with significant side effects. There is a window of opportunity to develop more specific agents, and to better understand ocular surface homeostasis to develop better-targeted biologics with fewer side effects.

Dr. Nicole Carnt
Prof. Dr. Fiona Stapleton
Prof. Dr. Eric Pearlman
Dr. Connie Tam
Guest Editors

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Keywords

risk factors
epidemiology
keratitis
conjunctivitis
keratoconjunctivitis
diagnosis
treatment
ocular surface
infection
inflammation
prevention
prophylaxis

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Published Papers (11 papers)

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Research

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10 pages, 1481 KiB

Open AccessArticle

Sodium Metabisulfite Inhibits Acanthamoeba Trophozoite Growth through Thiamine Depletion

by Ronnie Mooney, Elisa Giammarini, Erin Corbett, Scott Thomson, Kevin McKinley, Paula Sinisterra Sebastian, Kiri Rodgers, Jana O’Donnell, Charles McGinness, Craig W. Roberts, Kanna Ramaesh and Fiona L. Henriquez

Pathogens 2024, 13(6), 431; https://doi.org/10.3390/pathogens13060431 - 21 May 2024

Viewed by 1372

Abstract

Acanthamoeba keratitis (AK) is a severe infection of the cornea. Prevention and treatment are difficult due to the inefficacy of currently available compounds. The impact of many commonly used compounds for routine examinations of Acanthamoeba is unexplored but might offer insight useful in combatting AK. In this study, we demonstrate that sodium metabisulfite, a common preservation constituent of eye care solutions, was found to be active against Acanthamoeba trophozoites at concentrations lower than that commonly found in eye drops (IC₅₀ 0.03 mg/mL). We demonstrate that sodium metabisulfite depletes thiamine from growth medium and that Acanthamoeba is a thiamine auxotroph, requiring thiamine salvage for growth. The inhibitory effects of sodium metabisulfite can be overcome by thiamine supplementation. These results are consistent with the lack of key enzymes for thiamine biosynthesis in the genome of Acanthamoeba, an area which might prove exploitable using new or existing compounds. Indeed, this study highlights sodium metabisulfite as a useful inhibitor of Acanthamoeba castellanii trophozoites in vitro and that it acts, at least in part, by limiting available thiamine. Full article

(This article belongs to the Special Issue Advances in Ocular Surface Infections)

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11 pages, 843 KiB

Open AccessArticle

Epidemiology and Economic Cost Analysis of Microbial Keratitis from a Tertiary Referral Hospital in Australia

by Jason Richard Daley, Matthew Kyu Lee, Xingdi Wang, Matin Ly and Chameen Samarawickrama

Pathogens 2023, 12(3), 413; https://doi.org/10.3390/pathogens12030413 - 5 Mar 2023

Cited by 3 | Viewed by 2259

Abstract

Microbial keratitis is the most common cause of infective vision loss. The causative organism varies by region, and most cases require intensive antimicrobial therapy. The purpose of this study was to analyse the causative organisms of microbial keratitis, its presentation and economic burden from a tertiary referral hospital in Australia. A retrospective review of 160 cases of microbial keratitis was performed, over a 5-year period from 2015–2020. A wide variety of costs were considered to determine the economic burden, using standardized data from the Independent Hospital Pricing Authority and the cost of personal income loss. Our study showed the most commonly occurring pathogens were Herpes Simplex (16%), Staphylococcus aureus (15.1%) and Pseudomonas aeruginosa (14.3%). A total of 59.3% of patients were admitted, with a median length of admission of 7 days. Median cost for all presentations of microbial keratitis was AUD 8013 (USD 5447), with costs significantly increasing with admission. The total annual cost of microbial keratitis within Australia is estimated to be AUD 13.58 million (USD 9.23 million). Our findings demonstrate that microbial keratitis represents a significant economic burden for eye-related diseases and the key driving factor for the cost is the length of admission. Minimizing the duration of admission, or opting for outpatient management where appropriate, would significantly reduce the cost of treatment for microbial keratitis. Full article

(This article belongs to the Special Issue Advances in Ocular Surface Infections)

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16 pages, 344 KiB

Open AccessArticle

Association of Single-Nucleotide Polymorphisms in Interleukin Genes with Microbial Keratitis in a South Indian Population

by Nagaraju Konda, Subhabrata Chakrabarti, Prashant Garg and Mark D. P. Willcox

Pathogens 2022, 11(11), 1387; https://doi.org/10.3390/pathogens11111387 - 20 Nov 2022

Cited by 2 | Viewed by 2085

Abstract

Background: To examine the relationship between single-nucleotide polymorphisms (SNPs) in interleukin (IL) genes and keratitis and its clinical manifestations. Methods: SNPs in IL1B, IL6, CXCL8, IL10, and IL12B were analysed. Differences in frequencies of alleles, genotypes and haplotypes between cases and controls as well as associations between SNPs and clinical variables were calculated by χ2 tests with odds ratios. Results: The minor homologous genotype in IL1B rs16944 (p = 0.036; odds ratio (OR) = 2.063, 95% confidence interval (CI): 1.048–4.061) and CXCL8 rs4073 (p = 0.041; OR = 0.463, 95% CI: 0.224–0.956) and the heterologous genotypes in IL6 rs1800795 (p = 0.046; OR = 0.563, 95% CI: 0.326–0.972) and IL12B rs2569254 (p = 0.0446; OR = 0.557, 95% CI: 0.314–0.989) or rs730691 (p = 0.0051; OR = 0.451, 95% CI: 0.260–0.784) were associated with keratitis. The minor genotype of rs16944 was associated with severe infection (p = 0.046). The heterologous genotype in rs2569254 was associated with hospital admission, photophobia, and mode of contact lens wear (p ≤ 0.041). The heterologous genotype in rs730691 was associated with blurred vision, discharge, anterior chamber reaction, and mode of wear (p ≤ 0.047). Conclusions: This study demonstrates that SNPs in IL1B and CXCL8 are associated with risk of developing keratitis. The study also found relationships between SNPs and clinical measures of keratitis. The potential for ethnic differences in frequency of SNPs and their association with keratitis should be followed up using different populations. Full article

(This article belongs to the Special Issue Advances in Ocular Surface Infections)

17 pages, 1898 KiB

Open AccessArticle

Surveillance of Amoebic Keratitis-Causing Acanthamoebae for Potential Bacterial Endosymbionts in Ontario, Canada

by Nessika Karsenti, Andrew Purssell, Rachel Lau, Filip Ralevski, Shveta Bhasker, Hira Raheel and Andrea K. Boggild

Pathogens 2022, 11(6), 661; https://doi.org/10.3390/pathogens11060661 - 8 Jun 2022

Cited by 1 | Viewed by 2555

Abstract

Acanthamoeba spp. are the causative pathogens of several infections, including amoebic keratitis (AK), a vision-threatening infection. Acanthamoebae from corneal specimens of patients with AK harbor bacterial endosymbionts, which may increase virulence. We sought to understand the spectrum of bacterial endosymbionts present in clinical isolates of Acanthamoeba spp. identified in our reference parasitology laboratory. Isolates of Acanthamoeba spp. obtained from our biobank of anonymized corneal scrapings were screened for potential endosymbionts by PCR using primer pairs detecting bacteria belonging to orders Chlamydiales, Rickettsiales, or Legionellales and pan16S primers. Three primer pairs specific to the 18s rRNA gene of Acanthamoeba spp. were used for the amplification of Acanthamoeba DNA used for sequencing. Sanger sequencing of all PCR products was performed, followed by BLAST analysis for species identification. We screened 26 clinical isolates of Acanthamoeba spp. for potential endosymbionts. Five isolates (19%) were found to contain bacterial DNA belonging to Legionellales. Three (11%) contained members of the Rickettsiales and Pseudomonas genticulata was detected in a Rickettsia-positive sample. One strain (4%) contained Neochlamydia hartmannellae, a member of the Chlamydiales order. Bacterial endosymbionts are prevalent in clinical strains of Acanthamoeba causing AK isolated from corneal scrapings. The demonstration of these organisms in clinical Acanthamoeba isolates supports a potential exploration of anti-endosymbiont therapeutics as an adjuvant therapy in the treatment of AK. Full article

(This article belongs to the Special Issue Advances in Ocular Surface Infections)

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14 pages, 1388 KiB

Open AccessArticle

Antiviral Activity of Contemporary Contact Lens Care Solutions against Two Human Seasonal Coronavirus Strains

by Christiane Lourenco Nogueira, Scott Joseph Boegel, Manish Shukla, William Ngo, Lyndon Jones and Marc G. Aucoin

Pathogens 2022, 11(4), 472; https://doi.org/10.3390/pathogens11040472 - 15 Apr 2022

Cited by 6 | Viewed by 2890

Abstract

Background: Given that reports have suggested SARS-CoV-2 can be transmitted via conjunctiva, the ability of contact lens (CL) care products to reduce the infectiousness of two seasonal human coronavirus (HCoV) (HCoV-229E and HCoV-OC43) surrogates for SARS-CoV-2 was investigated. Methods: Biotrue and Boston Simplus (Bausch&Lomb), OPTI-FREE Puremoist and Clear Care (Alcon), and cleadew and cleadew GP (Ophtecs) were tested. Their ability to inactivate HCoV was evaluated using contact times of 4 and 6 h as well as 1% and 10% of virus inoculum. Results: Non-oxidative systems (Biotrue, Boston Simplus, and OPTI-FREE) did not exhibit a significant log₁₀ reduction compared to controls for the two viral strains for either incubation time (all p > 0.05) when 10% tests were performed. For the 1% test, while Boston Simplus and OPTI-FREE exhibited a significant log₁₀ reduction of both HCoV-229E (after 6 h) and HCoV-OC43 (after either 4 or 6 h incubation), those products showed less than 1 log₁₀ reduction of the two infectious viruses. Oxidative systems based on hydrogen peroxide or povidone-iodine showed a significant log₁₀ reduction compared with the controls for both HCoV-229E and HCoV-OC43 in all tested conditions (all p < 0.01). Clear Care led to virus inactivation to below the limit of quantification for tests performed with 1% of inoculum after 6 h incubation, while cleadew and cleadew GP led to inactivation of the two viruses to below the limit of quantification in all tested conditions. Conclusion: Oxidative CL disinfection systems showed significant virucidal activity against HCoV-229E and HCoV-OC43, while non-oxidative systems showed minimal ability to inactivate the HCoV species examined. Full article

(This article belongs to the Special Issue Advances in Ocular Surface Infections)

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Review

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15 pages, 957 KiB

Open AccessReview

Epidemiology of and Genetic Factors Associated with Acanthamoeba Keratitis

by Muhammad Ilyas, Fiona Stapleton, Mark D. P. Willcox, Fiona Henriquez, Hari Kumar Peguda, Binod Rayamajhee, Tasbiha Zahid, Constantinos Petsoglou and Nicole A. Carnt

Pathogens 2024, 13(2), 142; https://doi.org/10.3390/pathogens13020142 - 4 Feb 2024

Cited by 2 | Viewed by 2639

Abstract

Acanthamoeba keratitis (AK) is a severe, rare protozoal infection of the cornea. Acanthamoeba can survive in diverse habitats and at extreme temperatures. AK is mostly seen in contact lens wearers whose lenses have become contaminated or who have a history of water exposure, and in those without contact lens wear who have experienced recent eye trauma involving contaminated soil or water. Infection usually results in severe eye pain, photophobia, inflammation, and corneal epithelial defects. The pathophysiology of this infection is multifactorial, including the production of cytotoxic proteases by Acanthamoeba that degrades the corneal epithelial basement membrane and induces the death of ocular surface cells, resulting in degradation of the collagen-rich corneal stroma. AK can be prevented by avoiding risk factors, which includes avoiding water contact, such as swimming or showering in contact lenses, and wearing protective goggles when working on the land. AK is mostly treated with an antimicrobial therapy of biguanides alone or in combination with diaminidines, although the commercial availability of these medicines is variable. Other than anti-amoeba therapies, targeting host immune pathways in Acanthamoeba disease may lead to the development of vaccines or antibody therapeutics which could transform the management of AK. Full article

(This article belongs to the Special Issue Advances in Ocular Surface Infections)

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14 pages, 941 KiB

Open AccessReview

Microbial Adherence to Contact Lenses and Pseudomonas aeruginosa as a Model Organism for Microbial Keratitis

by Allison Campolo, Reed Pifer, Paul Shannon and Monica Crary

Pathogens 2022, 11(11), 1383; https://doi.org/10.3390/pathogens11111383 - 19 Nov 2022

Cited by 7 | Viewed by 3698

Abstract

Microbial keratitis (MK), the infection of the cornea, is a devastating disease and the fifth leading cause of blindness and visual impairment around the world. The overwhelming majority of MK cases are linked to contact lens wear combined with factors which promote infection such as corneal abrasion, an immunocompromised state, improper contact lens use, or failing to routinely disinfect lenses after wear. Contact lens-related MK involves the adherence of microorganisms to the contact lens. Therefore, this review discusses the information currently available regarding the disease pathophysiology, the common types of microorganisms causing MK, physical and organic mechanisms of adhesion, material properties which are involved in adhesion, and current antimicrobial strategies. This review also concludes that Pseudomonas aeruginosa is a model organism for the investigation of contact lens microbial adherence due to its prevalence in MK cases, its extremely robust adhesion, antimicrobial-resistant properties, and the severity of the disease it causes. Full article

(This article belongs to the Special Issue Advances in Ocular Surface Infections)

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10 pages, 758 KiB

Open AccessReview

Targeting Inflammation Driven by HMGB1 in Bacterial Keratitis—A Review

by Linda D. Hazlett, Sharon McClellan, Mallika Somayajulu and Denise Bessert

Pathogens 2021, 10(10), 1235; https://doi.org/10.3390/pathogens10101235 - 25 Sep 2021

Cited by 14 | Viewed by 2735

Abstract

Pseudomonas (P.) aeruginosa is a Gram-negative bacteria that causes human infections. It can cause keratitis, a severe eye infection, that develops quickly and is a major cause of ulceration of the cornea and ocular complications globally. Contact lens wear is the greatest causative reason in developed countries, but in other countries, trauma and predominates. Use of non-human models of the disease are critical and may provide promising alternative argets for therapy to bolster a lack of new antibiotics and increasing antibiotic resistance. In this regard, we have shown promising data after inhibiting high mobility group box 1 (HMGB1), using small interfering RNA (siRNA). Success has also been obtained after other means to inhinit HMGB1 and include: use of HMGB1 Box A (one of three HMGB1 domains), anti-HMGB1 antibody blockage of HMGB1 and/or its receptors, Toll like receptor (TLR) 4, treatment with thrombomodulin (TM) or vasoactive intestinal peptide (VIP) and glycyrrhizin (GLY, a triterpenoid saponin) that directly binds to HMGB1. ReducingHMGB1 levels in P. aeruginosa keratitis appears a viable treatment alternative. Full article

(This article belongs to the Special Issue Advances in Ocular Surface Infections)

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Other

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9 pages, 1138 KiB

Open AccessBrief Report

In Vitro Effectiveness of Soft Contact Lens Solutions Available on the Dutch Market against Acanthamoeba Species

by Anna C. Randag, Lieke de Kroon, Henny Otten, Cindy Arias Claro-Handgraaf, Barbara Schimmer, Titia Kortbeek, Jeroen van Rooij and Foekje F. Stelma

Pathogens 2023, 12(2), 214; https://doi.org/10.3390/pathogens12020214 - 29 Jan 2023

Cited by 3 | Viewed by 1799

Abstract

Acanthamoeba keratitis is almost universally associated with contact lens (CL) use. Until today, however, CL solution manufacturing protocols lack testing of anti-amoebic activity. This study investigates the effectiveness of CL solutions available on the Dutch market against trophozoites and cysts of Acanthamoeba castellanii and Acanthamoeba polyphaga. Sixteen CL solutions were tested: 13 multiple purpose solutions (MPS), 2 hydrogen peroxidase solutions (HPS) and 1 povidone-iodine-based solution (PIS). The Spearman–Karber (SK) log reduction method and an XTT colorimetric assay were used to evaluate the effectiveness at the manufacturer’s minimum recommended disinfection time (MMRDT) and after eight hours. At the MMRDT, one MPS showed an SK mean log reduction (MLR) of >3.0 against A. castellanii trophozoites. Two additional MPS and both HPS reached this threshold after eight hours. The SK MLR values for A. polyphaga trophozoites were between 1 and 3 at all time points. Using the XTT colorimetric assay, only HPS 1 showed >99.9% reduction (equivalent to 3 log reduction) in metabolic activity of A. castellanii trophozoites after eight hours. For A. polyphaga, both HPS and PIS showed a metabolic reduction of >99.9% after eight hours. Cysts were resistant against all solutions. We conclude that following the manufacturer’s guidelines, few solutions provide sufficient effectiveness against Acanthamoeba trophozoites and none against cysts. The results underline the importance of adequate hygiene when handling CLs. Full article

(This article belongs to the Special Issue Advances in Ocular Surface Infections)

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5 pages, 1922 KiB

Open AccessCase Report

Therapeutic Penetrating Keratoplasty in a Case of Corneal Perforation Caused by Colletotrichum gloeosporioides Infection

by Kazuki Imai, Takayoshi Sumioka, Hiroki Iwanishi, Yukihisa Takada, Shin’ichi Murata, Ryuta Iwamoto, Yuka Okada and Shizuya Saika

Pathogens 2022, 11(5), 526; https://doi.org/10.3390/pathogens11050526 - 29 Apr 2022

Cited by 3 | Viewed by 2030

Abstract

Background: Corneal infection of Colletotrichum gloeosporioides is uncommon and usually limited to the anterior stroma. However, we observed a case of corneal stromal perforation caused by this fungus under a compromised condition. Case: A 73-year-old woman consulted us with a severe corneal ulceration. She was a tangerine orange farmer who suffered from rheumatoid arthritis for more than ten years. Before consultation with us, she received pterygium excision in her right eye. She then developed a corneal ulceration and received topical glucocorticoid therapy upon diagnosis of rheumatoid arthritis-related stromal ulcer in the eye. At the first consultation with us, a corneal ulceration was observed in the inferotemporal area of her right cornea. Biological examination detected a filamentous fungus, Colletotrichum gloeosporioides. Topical and systemic antifungal treatments were not significantly effective. Fourteen days after consultation, the lesion grew worse, leading to stromal perforation, which was treated by therapeutic penetrating keratoplasty using a preserved corneal button. Conclusions: Topical glucocorticoid could accelerate the growth of Colletotrichum gloeosporioides before diagnosis, even though the primary cause of corneal ulceration development might be rheumatoid arthritis. Full article

(This article belongs to the Special Issue Advances in Ocular Surface Infections)

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10 pages, 948 KiB

Open AccessSystematic Review

Diagnostic Considerations for Non-Acanthamoeba Amoebic Keratitis and Clinical Outcomes

by Siobhan Moran, Ronnie Mooney and Fiona L. Henriquez

Pathogens 2022, 11(2), 219; https://doi.org/10.3390/pathogens11020219 - 8 Feb 2022

Cited by 5 | Viewed by 2050

Abstract

Cases of amoebic keratitis involving species other than Acanthamoeba are hypothesised to be underdiagnosed and poorly understood. Amoebic keratitis is debilitating and associated with chronic visual impairment. Understanding associated symptoms of non-Acanthamoeba amoebic keratitis could facilitate new diagnostic procedures and enable prompt treatment, ultimately leading to improved patient outcomes. Thus, a review of the literature was undertaken surrounding non-Acanthamoeba amoebic keratitis. Cases were geographically widespread and mostly confined to contact lens wearers ≤ 30 years old exposed to contaminated water sources and/or demonstrating poor lens hygiene. Vermamoeba vermiformis (previously Hartmanella vermiformis) was the most common causative agent, and a moderate number of mixed keratitis cases were also reported. A crucial disease indicator was early onset stromal deterioration/ulcerations, reported in 10 of the studies, usually only occurring in advanced Acanthamoeba keratitis. Mixed infections were the most difficult to treat, often requiring keratoplasty after unsuccessful combination treatment regimens. New diagnostic measures for non-Acanthamoeba amoebic keratitis should consider early onset stromal disease as a key disease indicator. Deep corneal scrapes are also necessary for accurate amoebic identification. Moreover, a combination approach to diagnosis is advised and should involve culture, microscopy and PCR techniques. In vitro drug sensitivity tests should also be conducted to help develop patient-specific treatment regimes. Full article

(This article belongs to the Special Issue Advances in Ocular Surface Infections)

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