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Progress in Retinal and Eye Research Jan 2013Herpes simplex virus-1 (HSV-1) infects the majority of the world's population. These infections are often asymptomatic, but ocular HSV-1 infections cause multiple... (Review)
Review
Herpes simplex virus-1 (HSV-1) infects the majority of the world's population. These infections are often asymptomatic, but ocular HSV-1 infections cause multiple pathologies with perhaps the most destructive being herpes stromal keratitis (HSK). HSK lesions, which are immunoinflammatory in nature, can recur throughout life and often cause progressive corneal scaring resulting in visual impairment. Current treatment involves broad local immunosuppression with topical steroids along with antiviral coverage. Unfortunately, the immunopathologic mechanisms defined in animal models of HSK have not yet translated into improved therapy. Herein, we review the clinical epidemiology and pathology of the disease and summarize the large amount of basic research regarding the immunopathology of HSK. We examine the role of the innate and adaptive immune system in the clearance of virus and the destruction of the normal corneal architecture that is typical of HSK. Our goal is to define current knowledge of the pathogenic mechanisms and recurrent nature of HSK and identify areas that require further study.
Topics: Antiviral Agents; Cornea; DNA, Viral; Herpesvirus 1, Human; Humans; Keratitis, Herpetic
PubMed: 22944008
DOI: 10.1016/j.preteyeres.2012.08.002 -
The Ocular Surface Jan 2019Herpes simplex virus type 1 (HSV) keratitis is a leading cause of infectious blindness. Clinical disease occurs variably throughout the cornea from epithelium to... (Review)
Review
Herpes simplex virus type 1 (HSV) keratitis is a leading cause of infectious blindness. Clinical disease occurs variably throughout the cornea from epithelium to endothelium and recurrent HSV stromal keratitis is associated with corneal scarring and neovascularization. HSV keratitis can be associated with ocular pain and subsequent neutrophic keratopathy. Host cell interactions with HSV trigger an inflammatory cascade responsible not only for clearance of virus but also for progressive corneal opacification due to inflammatory cell infiltrate, angiogenesis, and corneal nerve loss. Current antiviral therapies target viral replication to decrease disease duration, severity and recurrence, but there are limitations to these agents. Therapies directed towards viral entry into cells, protein synthesis, inflammatory cytokines and vascular endothelial growth factor pathways in animal models represent promising new approaches to the treatment of recurrent HSV keratitis.
Topics: Animals; Cornea; DNA, Viral; Eye Infections, Viral; Host-Pathogen Interactions; Humans; Immunity, Cellular; Inflammation; Keratitis, Herpetic; Simplexvirus
PubMed: 30317007
DOI: 10.1016/j.jtos.2018.10.002 -
Progress in Retinal and Eye Research May 2020Contact lenses represent a widely utilized form of vision correction with more than 140 million wearers worldwide. Although generally well-tolerated, contact lenses can... (Review)
Review
Contact lenses represent a widely utilized form of vision correction with more than 140 million wearers worldwide. Although generally well-tolerated, contact lenses can cause corneal infection (microbial keratitis), with an approximate annualized incidence ranging from ~2 to ~20 cases per 10,000 wearers, and sometimes resulting in permanent vision loss. Research suggests that the pathogenesis of contact lens-associated microbial keratitis is complex and multifactorial, likely requiring multiple conspiring factors that compromise the intrinsic resistance of a healthy cornea to infection. Here, we outline our perspective of the mechanisms by which contact lens wear sometimes renders the cornea susceptible to infection, focusing primarily on our own research efforts during the past three decades. This has included studies of host factors underlying the constitutive barrier function of the healthy cornea, its response to bacterial challenge when intrinsic resistance is not compromised, pathogen virulence mechanisms, and the effects of contact lens wear that alter the outcome of host-microbe interactions. For almost all of this work, we have utilized the bacterium Pseudomonas aeruginosa because it is the leading cause of lens-related microbial keratitis. While not yet common among corneal isolates, clinical isolates of P. aeruginosa have emerged that are resistant to virtually all currently available antibiotics, leading the United States CDC (Centers for Disease Control) to add P. aeruginosa to its list of most serious threats. Compounding this concern, the development of advanced contact lenses for biosensing and augmented reality, together with the escalating incidence of myopia, could portent an epidemic of vision-threatening corneal infections in the future. Thankfully, technological advances in genomics, proteomics, metabolomics and imaging combined with emerging models of contact lens-associated P. aeruginosa infection hold promise for solving the problem - and possibly life-threatening infections impacting other tissues.
Topics: Anti-Bacterial Agents; Bacteria; Contact Lenses; Cornea; Eye Infections, Bacterial; Humans; Keratitis; Prosthesis-Related Infections
PubMed: 31756497
DOI: 10.1016/j.preteyeres.2019.100804 -
Seminars in Immunology May 2023Fusarium, Aspergillus and Candida are important fungal pathogens that cause visual impairment and blindness in the USA and worldwide. This review will summarize the... (Review)
Review
Fusarium, Aspergillus and Candida are important fungal pathogens that cause visual impairment and blindness in the USA and worldwide. This review will summarize the epidemiology and clinical features of corneal infections and discuss the immune and inflammatory responses that play an important role in clinical disease. In addition, we describe fungal virulence factors that are required for survival in infected corneas, and the activities of neutrophils in fungal killing, tissue damage and cytokine production.
Topics: Humans; Fungi; Cornea; Keratitis; Fusarium; Neutrophils
PubMed: 37060806
DOI: 10.1016/j.smim.2023.101753 -
Viruses Feb 2021Human adenoviruses cause disease at multiple mucosal sites, including the respiratory, gastrointestinal, and genitourinary tracts, and are common agents of... (Review)
Review
Human adenoviruses cause disease at multiple mucosal sites, including the respiratory, gastrointestinal, and genitourinary tracts, and are common agents of conjunctivitis. One site of infection that has received sparse attention is the cornea, a transparent tissue and the window of the eye. While most adenovirus infections are self-limited, corneal inflammation (keratitis) due to adenovirus can persist or recur for months to years after infection, leading to reduced vision, discomfort, and light sensitivity. Topical corticosteroids effectively suppress late adenovirus keratitis but are associated with vision-threatening side effects. In this short review, we summarize current knowledge on infection of the cornea by adenoviruses, including corneal epithelial cell receptors and determinants of corneal tropism. We briefly discuss mechanisms of stromal keratitis due to adenovirus infection, and review an emerging therapy to mitigate adenovirus corneal infections based on evolving knowledge of corneal epithelial receptor usage.
Topics: Adenoviridae Infections; Adenoviruses, Human; Animals; Cornea; Corneal Diseases; Humans
PubMed: 33668417
DOI: 10.3390/v13020293 -
Transactions of the American... 2001To determine the risk factors and clinical signs of Curvularia keratitis and to evaluate the management and outcome of this corneal phaeohyphomycosis. (Review)
Review
PURPOSE
To determine the risk factors and clinical signs of Curvularia keratitis and to evaluate the management and outcome of this corneal phaeohyphomycosis.
METHODS
We reviewed clinical and laboratory records from 1970 to 1999 to identify patients treated at our institution for culture-proven Curvularia keratitis. Descriptive statistics and regression models were used to identify variables associated with the length of antifungal therapy and with visual outcome. In vitro susceptibilities were compared to the clinical results obtained with topical natamycin.
RESULTS
During the 30-year period, our laboratory isolated and identified Curvularia from 43 patients with keratitis, of whom 32 individuals were treated and followed up at our institute and whose data were analyzed. Trauma, usually with plants or dirt, was the risk factor in one half; and 69% occurred during the hot, humid summer months along the US Gulf Coast. Presenting signs varied from superficial, feathery infiltrates of the central cornea to suppurative ulceration of the peripheral cornea. A hypopyon was unusual, occurring in only 4 (12%) of the eyes but indicated a significantly (P = .01) increased risk of subsequent complications. The sensitivity of stained smears of corneal scrapings was 78%. Curvularia could be detected by a panfungal polymerase chain reaction. Fungi were detected on blood or chocolate agar at or before the time that growth occurred on Sabouraud agar or in brain-heart infusion in 83% of cases, although colonies appeared only on the fungal media from the remaining 4 sets of specimens. Curvularia was the third most prevalent filamentous fungus among our corneal isolates and the most common dematiaceous mold. Corneal isolates included C senegalensis, C lunata, C pallescens, and C prasadii. All tested isolates were inhibited by 4 micrograms/mL or less of natamycin. Topical natamycin was used for a median duration of 1 month, but a delay in diagnosis beyond 1 week doubled the average length of topical antifungal treatment (P = .005). Visual acuity improved to 20/40 or better in 25 (78%) of the eyes.
CONCLUSIONS
Curvularia keratitis typically presented as superficial feathery infiltration, rarely with visible pigmentation, that gradually became focally suppurative. Smears of corneal scrapings often disclosed hyphae, and culture media showed dematiaceous fungal growth within 1 week. Natamycin had excellent in vitro activity and led to clinical resolution with good vision in most patients with corneal curvulariosis. Complications requiring surgery were not common but included exophytic inflammatory fungal sequestration, treated by superficial lamellar keratectomy, and corneal perforation, managed by penetrating keratoplasty.
Topics: Adolescent; Adult; Aged; Antifungal Agents; Ascomycota; Child; Cornea; DNA, Fungal; Debridement; Eye Infections, Fungal; Female; Humans; Keratitis; Male; Middle Aged; Mycoses; Polymerase Chain Reaction; Risk Factors; Seasons
PubMed: 11797300
DOI: No ID Found -
Experimental Eye Research Jan 2021Acanthamoeba keratitis (AK) is a rare protozoal infection of the cornea. At least eight species of Acanthamoeba are known to cause this sight-threatening disease of the... (Review)
Review
Acanthamoeba keratitis (AK) is a rare protozoal infection of the cornea. At least eight species of Acanthamoeba are known to cause this sight-threatening disease of the ocular surface. Acanthamoeba spp. exist in a wide array of niches ranging from thermal springs to under ice and every conceivable habitat in between. Contact lens wear is the leading risk factor for AK and is practiced by over 30 million individuals in the United States, yet the incidence of AK is less than 33 cases per one million contact lens wearers. Serological studies have reported that 90%-100% of individuals with no history of AK possess antibodies specific for Acanthamoeba antigens indicating that exposure to this organism is commonplace, yet disease is remarkably rare. Animal studies have shed light on the pathobiology and immunobiology of AK and indicate that a constellation of factors including the ocular surface microbiome and the microbiome of Acanthamoeba itself contribute to the pathogenesis of AK. Interesting, secretory antibodies produced by the adaptive immune response can prevent the initiation of corneal infection, but once Acanthamoeba trophozoites breach the corneal epithelium the adaptive immune system is helpless in altering the course of AK. It has been almost 50 years since AK was first described, yet many questions remain unanswered about this curious and enigmatic disease of the ocular surface.
Topics: Acanthamoeba; Acanthamoeba Keratitis; Animals; Antibodies, Protozoan; Contact Lenses; Cornea; Eye Infections, Parasitic; Humans; Risk Factors
PubMed: 33221372
DOI: 10.1016/j.exer.2020.108365 -
Indian Journal of Ophthalmology May 2022To report a new entity called "toxic non-inflammatory fungal keratitis."
PURPOSE
To report a new entity called "toxic non-inflammatory fungal keratitis."
METHODS
Eyes manifesting infective keratitis with a history of prior administration of topical steroids were included in the study. The details pertaining to the type of injury, duration of injury, and primary treatment for corneal trauma were meticulously documented. The corneal tissues were scraped from the patients and were analyzed for fungal filaments by using a 10% KOH mount under a compound microscope. Moreover, these scraped materials were plated on blood agar and Sabouraud dextrose agar plates.
RESULTS
The corneal ulcers displayed a disproportionately reduced intensity of pain and improved visual acuity. Further, 10% KOH revealed profuse fungal filaments with few inflammatory cells in all the patients. The anterior chamber cells and flare were either reduced or entirely absent. There was no evidence of lid edema and surrounding corneal edema in any of the patients. The mean healing period was 28.8 days (standard deviation (SD): 10.05). The KOH mount revealed the presence of confluent fungal hyphae with a few inflammatory cell infiltrates. The Aspergillus species and Fusarium species were found in 47% and 40% of the cases, respectively.
CONCLUSION
Toxic non-inflammatory fungal keratitis following steroid therapy needs to be considered in fungal ulcers with disproportionately less pain and good visual acuity. The fungal ulcers with altered clinical signs of classical inflammation need to be assessed for topical steroid misuse.
Topics: Agar; Cornea; Corneal Ulcer; Eye Infections, Fungal; Fungi; Humans; Keratitis; Pain; Steroids; Ulcer
PubMed: 35502029
DOI: 10.4103/ijo.IJO_2509_21 -
Experimental Eye Research Mar 2021There is a number of systemic diseases affecting the cornea. These include endocrine disorders (diabetes, Graves' disease, Addison's disease, hyperparathyroidism),... (Review)
Review
There is a number of systemic diseases affecting the cornea. These include endocrine disorders (diabetes, Graves' disease, Addison's disease, hyperparathyroidism), infections with viruses (SARS-CoV-2, herpes simplex, varicella zoster, HTLV-1, Epstein-Barr virus) and bacteria (tuberculosis, syphilis and Pseudomonas aeruginosa), autoimmune and inflammatory diseases (rheumatoid arthritis, Sjögren's syndrome, lupus erythematosus, gout, atopic and vernal keratoconjunctivitis, multiple sclerosis, granulomatosis with polyangiitis, sarcoidosis, Cogan's syndrome, immunobullous diseases), corneal deposit disorders (Wilson's disease, cystinosis, Fabry disease, Meretoja's syndrome, mucopolysaccharidosis, hyperlipoproteinemia), and genetic disorders (aniridia, Ehlers-Danlos syndromes, Marfan syndrome). Corneal manifestations often provide an insight to underlying systemic diseases and can act as the first indicator of an undiagnosed systemic condition. Routine eye exams can bring attention to potentially life-threatening illnesses. In this review, we provide a fairly detailed overview of the pathologic changes in the cornea described in various systemic diseases and also discuss underlying molecular mechanisms, as well as current and emerging treatments.
Topics: Autoimmune Diseases; COVID-19; Comorbidity; Cornea; Humans; SARS-CoV-2
PubMed: 33485845
DOI: 10.1016/j.exer.2021.108455 -
Cells Nov 2020Bacterial keratitis is a corneal infection which may cause visual impairment or even loss of the infected eye. It remains a major cause of blindness in the developing... (Review)
Review
Bacterial keratitis is a corneal infection which may cause visual impairment or even loss of the infected eye. It remains a major cause of blindness in the developing world. and are common causative agents and these bacterial species are known to colonise the corneal surface as biofilm populations. Biofilms are complex bacterial communities encased in an extracellular polymeric matrix and are notoriously difficult to eradicate once established. Biofilm bacteria exhibit different phenotypic characteristics from their planktonic counterparts, including an increased resistance to antibiotics and the host immune response. Therefore, understanding the role of biofilms will be essential in the development of new ophthalmic antimicrobials. A brief overview of biofilm-specific resistance mechanisms is provided, but this is a highly multifactorial and rapidly expanding field that warrants further research. Progression in this field is dependent on the development of suitable biofilm models that acknowledge the complexity of the ocular environment. Abiotic models of biofilm formation (where biofilms are studied on non-living surfaces) currently dominate the literature, but co-culture infection models are beginning to emerge. , and corneal infection models have now been reported which use a variety of different experimental techniques and animal models. In this review, we will discuss existing corneal infection models and their application in the study of biofilms and host-pathogen interactions at the corneal surface.
Topics: Biofilms; Cornea; Humans; Keratitis
PubMed: 33182687
DOI: 10.3390/cells9112450