Materiały źródłowe

• #1 Conjunctivitis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/sites/books/NBK541034/

  Conjunctivitis refers to the inflammation or infection of the conjunctiva. Conjunctivitis, the inflammation or infection of the conjunctiva, represents the most prevalent cause of eye redness in both primary care and the emergency department. This condition places a substantial burden on the healthcare system. Conjunctivitis is the most prevalent etiology of eye redness and discharge. The etiology of this condition could be infectious or noninfectious; the most common is viral conjunctivitis, followed by bacterial conjunctivitis, and among noninfectious etiologies, the most common etiologies are allergic and toxin-induced conjunctivitis. […] Conjunctivitis occurs when the conjunctiva becomes inflamed due to an infection or an irritant. As a result of this inflammation, the blood vessels in the conjunctiva dilate, causing redness or hyperemia, and the conjunctiva can also become swollen. The inflammation affects the entire conjunctiva, and depending on the cause, discharge may also be present. Bacterial conjunctivitis occurs when the eye’s surface tissues are colonized by normal flora like Staphylococci sp., Streptococci, and Corynebacteria. The epithelial covering of the conjunctiva is the primary defense mechanism against infection, and any disruption in this barrier can lead to infection. Secondary defense mechanisms include immune reactions carried out by the tear film immunoglobulins and lysozyme, conjunctival vasculature, and the rinsing action of blinking and lacrimation.

• #2 Conjunctivitis | AAFP

  https://www.aafp.org/pubs/afp/issues/1998/0215/p735.html

  Conjunctivitis refers to any inflammatory condition of the membrane that lines the eyelids and covers the exposed surface of the sclera. It is the most common cause of red eye. The etiology can usually be determined by a careful history and an ocular examination, but culture is occasionally necessary to establish the diagnosis or to guide therapy. Conjunctivitis is commonly caused by bacteria and viruses. Neisseria infection should be suspected when severe, bilateral, purulent conjunctivitis is present in a sexually active adult or in a neonate three to five days postpartum. Conjunctivitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae requires aggressive antibiotic therapy, but conjunctivitis due to other bacteria is usually self-limited. Chronic conjunctivitis is usually associated with blepharitis, recurrent styes or meibomianitis. Treatment requires good eyelid hygiene and the application of topical antibiotics as determined by culture. Allergic conjunctivitis is distinguished by severe itching and allergen exposure. This condition is generally treated with topical antihistamines, mast-cell stabilizers or anti-inflammatory agents.

• #3 Pink eye (conjunctivitis) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/pink-eye/symptoms-causes/syc-20376355

  Pink eye is the inflammation or infection of the transparent membrane that lines your eyelid and eyeball. […] Pink eye is an inflammation of the transparent membrane that lines the eyelid and eyeball. This membrane is called the conjunctiva. When small blood vessels in the conjunctiva become swollen and irritated, they’re more visible. This is what causes the whites of the eyes to appear reddish or pink. Pink eye also is called conjunctivitis. […] Most cases of pink eye are caused by adenovirus. It also can be caused by other viruses, including herpes simplex virus and varicella-zoster virus. […] Both viral and bacterial conjunctivitis can occur along with colds or symptoms of a respiratory infection, such as a sore throat. Wearing contact lenses that aren’t cleaned properly or aren’t your own can cause bacterial conjunctivitis.

• #4 Bacterial Conjunctivitis (Pink Eye): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1191730-overview

  The surface tissues of the eye and the ocular adnexa are colonized by normal flora such as streptococci, staphylococci, and corynebacteria. Alterations in the host defense, in the bacterial titer, or in the species of bacteria can lead to clinical infection. Alteration in the flora also can result from external contamination (eg, contact lens wear, swimming), the use of topical or systemic antibiotics, or spread from adjacent infectious sites (eg, rubbing of the eyes). […] The primary defense against infection is the epithelial layer covering the conjunctiva. Disruption of this barrier can lead to infection. Secondary defenses include hematologic immune mechanisms carried by the conjunctival vasculature, tear film immunoglobulins, and lysozyme and the rinsing action of lacrimation and blinking.

• #5 Bacterial Conjunctivitis | Ento Key

  https://entokey.com/bacterial-conjunctivitis/

  Bacterial conjunctivitis is a common form of ocular infection. The clinical characteristics and course of bacterial conjunctivitis are related primarily to the disease-producing capabilities of the infecting microbe, including its invasiveness and its ability to elaborate toxins. […] The pathogen elicits a hyperemic response, vascular stasis, cellular exudate, and vascular leakage producing edema. The intensity of these common responses varies with the organism and the host. Signs and symptoms include red eye, mucopurulent or purulent discharge, conjunctival thickening and chemosis, and a papillary reaction. Certain virulent organisms may produce marked lid edema, conjunctival hyperemia, and a copious, purulent, exudative response. Infections by other organisms are characterized by a membranous or pseudomembranous conjunctivitis. The membrane or pseudomembrane consists of condensed fibrin, inflammatory cells, and other exudates. A true membrane results from penetration of the fibrinous exudate into the epithelium, producing bleeding when peeled; pseudomembranes do not bleed when peeled. […] Although the clinical expression and severity of conjunctivitis is the result of the pathogenicity, virulence, invasiveness, and toxigenicity of an organism, the basic mechanism underlying each clinical expression is similar.

• #6 Diagnosis and treatment of hyperacute bacterial conjunctivitis – EyeWorld

  https://www.eyeworld.org/2018/diagnosis-and-treatment-of-hyperacute-bacterial-conjunctivitis/

  Hyperacute bacterial conjunctivitis requires prompt diagnosis and treatment because some types, specifically conjunctivitis caused by Neisseria gonorrhoeae or Neisseria meningitides, can cause corneal ulceration, corneal opacification, corneal perforation, and panophthalmitis. […] Hyperacute bacterial conjunctivitis is primarily due to Neisseria gonorrhoeae, which is a sexually transmitted disease, Dr. de Luise said. Neisseria meningitidis can also cause hyperacute bacterial conjunctivitis and can lead to potentially fatal meningeal or systemic infection. […] The causes of hyperacute bacterial conjunctivitis are almost always bacteria in the genus Neisseria. Neisseria gonorrhoeae or its cousin Neisseria meningitidis are often responsible, Dr. de Luise said. […] Dr. Mah added that Neisseria gonococcus is one of the rare pathogens that can penetrate a normal, intact corneal epithelium.

• #7 Diagnosis and treatment of hyperacute bacterial conjunctivitis – EyeWorld

  https://www.eyeworld.org/2018/diagnosis-and-treatment-of-hyperacute-bacterial-conjunctivitis/

  If the physician diagnoses hyperacute bacterial conjunctivitis, this can be a sexually transmitted disease by Neisseria gonorrhoeae bacteria, Dr. de Luise said. One should be worried about Neisseria gonorrhoeae, which is the gonococcus, or rarely Neisseria meningitidis, which is the meningococcus that causes meningitis. Neisseria meningitidis can cause a panophthalmitis and subsequent meningitis, which can be life-threatening if not treated promptly. […] He noted that the cornea is involved in almost half of the cases of hyperacute bacterial conjunctivitis. About 40% of the time, there is an ulceration or a perforation, which is a sight-threatening and life-threatening emergency. […] He added that all patients with hyperacute bacterial conjunctivitis need to be treated for gonococcus and for concomitant chlamydial infection, just in case. […] The chlamydia is not causing the hyperacute pus. Thats being caused by the Neisseria.

• #8 Viral Conjunctivitis

  https://www.mdpi.com/1999-4915/15/3/676

  Viruses account for 80% of all cases of acute conjunctivitis and adenovirus; enterovirus and herpes virus are the common causative agents. In general, viral conjunctivitis spreads easily. Therefore, to control the spread, it is crucial to quickly diagnose illnesses, strictly implement hand washing laws, and sanitize surfaces. Swelling of the lid margin and ciliary injection are subjective symptoms, and eye discharge is frequently serofibrinous. Preauricular lymph node swelling can occasionally occur. Approximately 80% of cases of viral conjunctivitis are caused by adenoviruses. Adenoviral conjunctivitis may become a big global concern and may cause a pandemic. Diagnosis of herpes simplex viral conjunctivitis is crucial for using corticosteroid eye solution as a treatment for adenovirus conjunctivitis. Although specific treatments are not always accessible, early diagnosis of viral conjunctivitis may help to alleviate short-term symptoms and avoid long-term consequences.

• #9 Pathogenesis and management of adenoviral keratoconjunctivitis | IDR

  https://www.dovepress.com/pathogenesis-and-management-of-adenoviral-keratoconjunctivitis-peer-reviewed-fulltext-article-IDR

  Major structural proteins of AdV include a homopentameric penton base that mediates AdV internalization into the host, a homotrimeric fiber protein that plays a role in viral attachment to host cellular receptors, and hexons that are recognized by neutralizing antibodies. Primary cellular receptors, such as CAR, CD46 (membrane cofactor protein), sialic acid, desmoglein 2, heparin sulfate proteoglycans, CD80, CD86, and GD1a, interact with fiber-knob protein to mediate adenoviral attachment to host cells. […] The presence of AdV on the ocular surface is associated with activation of ocular surface epithelial cells secreting interleukin 8 (IL8), which binds to its chemokine receptors CXCR1 and CXCR2. The subsequent phosphorylation of downstream molecules culminates in the translocation of CAR and v3 integrin from the basolateral surface of the polarized epithelial cell to the apical surface to enable interaction of AdV fiber knob with CAR on the apical surface of the epithelial cell.

• #10 Pathogenesis and management of adenoviral keratoconjunctivitis | IDR

  https://www.dovepress.com/pathogenesis-and-management-of-adenoviral-keratoconjunctivitis-peer-reviewed-fulltext-article-IDR

  Following adenoviral attachment, internalization of AdV into an endosome is mediated by the interaction of the homopentameric penton base and vitronectin-binding integrin. Penton base-integrin interaction activates an intracellular signaling cascade that culminates in the internalization of AdV into clathrin-coated vesicles. […] Following internalization of the adenoviral nucleocapsid into the endosome, acidification of the endosome is required to initiate several steps involved in the uncoating of AdV. It is of note that the acidic pH of the endosome triggers the AdV-uncoating process and penetration of the endosome. […] The replication cycle of AdV consists of an early stage and a late stage. The early stage of adenoviral replication is characterized by the generation of adenoviral E1A protein (encoded by the E1A gene) that transactivates other early genes E1B, E2, E3, and E4, which play important roles in the early stage of the AdV replication cycle.

• #11 Viral Conjunctivitis

  https://www.mdpi.com/1999-4915/15/3/676

  In the present review, we discuss the pathogenesis and management of viral conjunctivitis, which involves various symptoms. […] EKC occurs more frequently in adults than in children. The incubation period is approximately 10 days, and the main ocular feature is acute follicular conjunctivitis in clinical findings. Conjunctivitis is caused when a projecting fiber from the penton adheres to the receptor in the conjunctival epithelium. The virus enters cells and multiplies in the nuclei. The increasing inclusion bodies observed in the nucleus are comprised of viruses. When cells (filled with inclusion bodies) die, they release the virus. Follicles are formed on the conjunctiva as a result of the immune response of lymphocytes under the conjunctival epithelium. The multiplied virus is transported to the preauricular lymph node by lymphatic channels under the conjunctival epithelium. The swelling in the lymph nodes is attributable to the proliferation of antigen-specific lymphocytes.

• #12 Pathogenesis and management of adenoviral keratoconjunctivitis | IDR

  https://www.dovepress.com/pathogenesis-and-management-of-adenoviral-keratoconjunctivitis-peer-reviewed-fulltext-article-IDR

  The human immune system consists of many levels of defense against invasion by pathogens, including viruses. The epithelium of the ocular surface provides a physical barrier to invasion by viruses and constitutes the first level of defense against pathogens, including AdVs. […] Innate immunoresponse to adenoviral ocular infection is mediated by natural killer (NK) cells, monocytes, and type 1 interferon (IFN). Adaptive immunity is mediated by IgA, CD8 T cells, and T-helper 1 (TH1) cells. […] Although cell-mediated immunity is necessary for limiting viral growth, AdV is able to persist in the host via the use of immunoevasive strategies, such as inhibiting antiviral response mediated by IFNs, preventing cytolysis of AdV-infected cells by TNF, promoting intracellular survival by blocking apoptosis of infected cells and evading CTL-mediated cytolysis of infected cells by preventing the display of viral peptide complexed to major histocompatibility complex (MHC) class I molecules on the surface of virally infected cells.

• #12 Viral Conjunctivitis

  https://www.mdpi.com/1999-4915/15/3/676

  The surface of the corneal stroma experiences a subepithelial infiltration owing to a late-onset sensitivity reaction to the adenoviral antigen. Although cell infiltration occurs in the cornea, it appears that adenoviral growth does not. […] In conclusion, caution should be exercised because pediatric viral conjunctivitis infections may frequently occur come with pseudomembranes. Treatment for viral conjunctivitis is supportive in general. Adenovirus is responsible for the majority of cases of viral conjunctivitis. Management protocols for adenoviral conjunctivitis have not changed currently. Specific antiviral drugs may change the steps involved in the handling of this disease clinically. Cases of adenoviral conjunctivitis should be remarked on from now on. Herpetic conjunctivitis is treated by acyclovir ointment in general. Clinicians must be vigilant in identifying cases of conjunctivitis with acyclovir resistance. Steroids must be used with care, and a herpetic infection, which may get exacerbated following steroid administration, should be eliminated only after a thorough ophthalmologic examination. Increased viral replication may result from herpetic conjunctivitis treated with corticosteroids.

• #13 Allergic Conjunctivitis: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1191467-overview

  The ocular surface may exhibit a wide variety of immunologic responses resulting in inflammation of the conjunctiva and cornea. In the Gell and Coombs classification system for various immunologic hypersensitivity reactions, 5 types of reactions are recognized. The major type I hypersensitivity reactions involving the conjunctiva commonly are referred to as allergic conjunctivitis and are further subclassified into seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC). […] The presence of an antigen triggers the allergic cascade, and, thus, avoidance of the offending antigen is the primary behavioral modification for all types of allergic conjunctivitis. […] Type I (immediate) hypersensitivity reactions occur when a sensitized individual comes in contact with a specific antigen. Immunoglobulin E (IgE) has a strong affinity for mast cells, and the cross-linking of 2 adjacent IgE molecules by the antigen triggers mast cell degranulation.

• #14 Allergic Conjunctivitis: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1191467-overview

  The mast cells degranulation releases various preformed and newly formed mediators of the inflammatory cascade. Most notable of these inflammatory mediators are histamine, tryptase, chymase, heparin, chondroitin sulfate, prostaglandins, thromboxanes, and leukotrienes. These various inflammatory mediators, together with various chemotactic factors, result in an increase in vascular permeability and migration of eosinophils and neutrophils. This type I hypersensitivity reaction is the most common allergic response of the eye. […] A combination of type I and type IV hypersensitivity reactions may be responsible for the pathogenesis of GPC. It is believed that an antigen is present, in predisposed individuals, which stimulates the immunological reaction and the development of GPC.

• #15 Allergic conjunctivitis – Wikipedia

  https://en.wikipedia.org/wiki/Allergic_conjunctivitis

  The ocular allergic response is a cascade of events that is coordinated by mast cells. Beta chemokines such as eotaxin and MIP-1 alpha have been implicated in the priming and activation of mast cells in the ocular surface. When a particular allergen is present, sensitization takes place and prepares the system to launch an antigen specific response. TH2 differentiated T cells release cytokines, which promote the production of antigen specific immunoglobulin E (IgE). IgE then binds to IgE receptors on the surface of mast cells. Then, mast cells release histamine, which then leads to the release of cytokines, prostaglandins, and platelet-activating factor. Mast cell intermediaries cause an allergic inflammation and symptoms through the activation of inflammatory cells. […] When histamine is released from mast cells, it binds to H1 receptors on nerve endings and causes the ocular symptom of itching. Histamine also binds to H1 and H2 receptors of the conjunctival vasculature and causes vasodilatation. Mast cell-derived cytokines such as chemokine interleukin IL-8 are involved in recruitment of neutrophils. TH2 cytokines such as IL-5 recruit eosinophils and IL-4, IL-6, and IL-13, which promote increased sensitivity. Immediate symptoms are due to the molecular cascade. Encountering the allergen a patient is sensitive to leads to increased sensitization of the system and more powerful reactions. Advanced cases can progress to a state of chronic allergic inflammation.

• #16 Conjunctivitis – EyeWiki

  https://eyewiki.org/Conjunctivitis

  In perennial allergic conjunctivitis (PAC), the conjunctival tissue is infiltrated by eosinophils, neutrophils, and a small number of T cells, probably recruited as a result of the release of chemokines that attract these cells to the site of inflammation during the persistent, allergen-driven inflammatory response.

• #17 New study sheds light on the developmental mechanism of allergic conjunctivitis

  https://medicalxpress.com/news/2023-10-developmental-mechanism-allergic-conjunctivitis.html

  When it comes to eye allergies, the transition from allergen contact to bothersome symptoms has always been quick, appearing within a span of a few minutes. The initial stage of allergic conjunctivitis involves the penetration of allergen through the epithelial cell layer (cells covering the outer surface of the body). However, the exact mechanism underlying the rapid allergen transfer has remained a mystery so far. […] In this study, we aimed to further elucidate the roles of particulate allergens such as pollen shells in the development of allergic conjunctivitis. […] What they discovered was remarkable: the introduction of pollen shells into the eye triggered the rapid formation of what is known as „Goblet cell-associated antigen passages” (GAPs) within the conjunctiva. […] Our study shows that a nerve-driven goblet cell activation enables the rapid transport of allergen through conjunctiva and promotes allergic reaction.

• #18 New study sheds light on the developmental mechanism of allergic conjunctivitis

  https://medicalxpress.com/news/2023-10-developmental-mechanism-allergic-conjunctivitis.html

  This finding shed new light on how allergens quickly penetrate the eye’s defenses, leading to the rapid onset of allergic conjunctivitis. […] Furthermore, the researchers observed that the sensory nervous system played a vital role in this process. […] This highlighted the complex interplay between sensory nerves and the immune response in the development of allergic conjunctivitis. […] What sets this discovery apart is that it challenged the commonly held belief that muscarinic acetylcholine receptors regulate GAPs, as pollen shell-stimulated GAP formation remained unaffected by topical atropine. […] Moreover, the findings suggested that pollen shell-induced GAP can be a novel target for treatment of conjunctival disease. […] Understanding the role of goblet cells and GAPs in ocular sensitization represents a significant step towards providing relief for the millions of people affected by allergic eye conditions worldwide.

• #19 Toxic conjunctivitis – UpToDate

  https://www.uptodate.com/contents/toxic-conjunctivitis

  Toxic conjunctivitis (also called toxic keratoconjunctivitis) implies direct damage to ocular tissues from an offending agent, usually a preservative or medication. The toxic agent can cause a papillary or follicular response in the conjunctiva with chronic use, and the conjunctiva can become chemotic, edematous, and hyperemic. […] The most common form of toxic conjunctivitis is ocular surface medicamentosa (OSM). OSM is a chemical toxicity and/or a delayed, cell-mediated hypersensitivity response of the ocular surface and adnexa to active drugs and/or preservatives. […] Toxic conjunctivitis may take days to years to develop but typically occurs with protracted use of topical ocular medications (usually longer than three months but can vary with the type of medication). […] Certain topical medications and the preservatives in those medications, contact lens solutions, and artificial tears are the most common causes of toxic ocular reactions.

• #20 Current Knowledge in Allergic Conjunctivitis – Turkish Journal of Ophthalmology

  https://oftalmoloji.org/articles/current-knowledge-in-allergic-conjunctivitis/doi/tjo.galenos.2020.11456

  Allergic conjunctivitis is a disease of increasing prevalence that affects both children and adults and causes significant deterioration of their quality of life and sometimes irreversible visual damage. […] We review their clinical course, characteristics, and differential diagnosis, and highlight recent advances in their pathophysiology and treatment. […] Allergic conjunctivitis is the consequence of a type 1 allergic reaction. In sensitized individuals, when the allergen arrives at the conjunctiva it triggers the reaction: Th2-cells produce cytokines that induce immunoglobulin E (IgE) production by B-cells. The secreted IgE may bind to the membranes of mast cells and also to the allergen and provoke the secretion of inflammatory mediators. […] VKC is caused by type 1 (IgE-dependent) and type 4 (IgE-independent) immune pathogenic mechanisms. Patients with VKC have an increased number of activated CD4+ T-lymphocytes, and, characteristically, of Th2, suggesting a type 4 hypersensitivity reaction. […] The ocular surface microbiome has also been implicated in the disease. Conjunctival scrapings show eosinophilic infiltration, but also mast cells, which are the predominant cell type in the substantia propria and are specifically increased in this type of conjunctivitis, inflammatory cytokines such as interleukin (IL)-6 and IL-8, and growth factors may have a role in the disease.

• #21 Current Knowledge in Allergic Conjunctivitis – Turkish Journal of Ophthalmology

  https://oftalmoloji.org/articles/current-knowledge-in-allergic-conjunctivitis/doi/tjo.galenos.2020.11456

  AKC is a type 4 hypersensitivity immune reaction, with predominant participation of T-cells, and especially Th1-cells that produce chemotaxis and stimulate eosinophil production. Eosinophils initiate cytokine production, which heightens the inflammatory response. […] Recent studies suggest that microbes and especially colonization of the conjunctiva with Staphylococcus aureus may have a role in the disease. […] GPC is a chronic inflammatory disease that courses with giant papillae on the upper tarsal conjunctiva. […] However, mast cells, eosinophils, and basophils are found in the conjunctiva of GPC patients, and they also show an increase of various immunoglobulins and cytokines, especially eotaxin in the tears. […] In very recalcitrant cases of VKC and AKC, eye surgery may be needed. Papillae resection, in some cases with grafting of autologous conjunctiva, amniotic membrane or mucous membrane are effective in the treatment of severe forms of VKC with corneal ulcers.

• #22 Vernal keratoconjunctivitis | Eye

  https://www.nature.com/articles/6700675

  Vernal keratoconjunctivitis (VKC) is an allergic eye disease that especially affects young boys. […] On the basis of challenge studies as well as immunohistochemical and mediator studies, a Th2-driven mechanism with the involvement of mast cells, eosinophils, and lymphocytes has been suggested. […] Other studies have demonstrated the involvement of neural factors such as substance P and NGF in the pathogenesis of VKC, and the overexpression of oestrogen and progesterone receptors in the conjunctiva of VKC patients has introduced the possible involvement of sex hormones. Thus, the pathogenesis of VKC is probably multifactorial, with the interaction of the immune, nervous, and endocrine systems. […] Recent studies suggest a more complex non-IgE-dependent pathogenic mechanism. A multitude of cells and mediators have been detected in the serum, conjunctiva, and tears of patients with VKC, which may have a relevant role in the pathogenesis of the disease.

• #23 Vernal keratoconjunctivitis | Eye

  https://www.nature.com/articles/6700675

  In fact, skin tests and RAST are often negative in VKC and several patients do not have a personal or family history of atopy. […] On the basis of challenge studies as well as immunohistochemical and mediator studies, we recently suggested a Th2-driven mechanism and a definition, similar to that of asthma, of an allergic inflammatory disease of the conjunctiva with mast cells, eosinophils, and lymphocytes. […] It is possible that the pathogenesis of VKC is characterized by a Th2 lymphocyte alteration, while the exaggerated IgE response to common allergens is an inconsistent and, perhaps, secondary event. […] This cell recruitment (favoured by an overexpression of adhesion molecules) results in the release of other toxic cell mediators (such as eosinophil cationic protein, EDN/EPX) with corneal epithelial damage.

• #24 Vernal keratoconjunctivitis | Eye

  https://www.nature.com/articles/6700675

  Indeed, several inflammatory and epithelial cells may induce fibroblast proliferation and collagen production leading to the characteristic conjunctival findings. […] The existence of a relationship between the central nervous system and the eye is easily established when considering common anatomical and embryogenic origins. […] Whether neurotransmitters and neurotrophins may influence conjunctival inflammation is not clear at present. […] A role for sex hormones has been postulated in the pathogenesis of the disease. […] These hormones may bind to conjunctival receptors and exert a proinflammatory effect through the recruitment of eosinophils to the conjunctival tissue. […] Recently, new reports have improved the knowledge of the pathogenetic mechanisms of VKC. […] VKC was shown to be not solely IgE-mediated, but its pathogenesis is multifactorial, mediated by Th2 lymphocytes, eosinophils, IgE, mast cells, and a complex network of interleukins and cell mediators. […] The presence of increased serum levels of cytokines, enzymes, eosinophil-derived mediators, neuropeptides, and neurotrophins also suggests that this is a systemic, and not just a local, disease.

• #25 Relapsing viral keratoconjunctivitis in COVID-19: a case report | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/s12985-020-01370-6

  In this case report, the pathogenesis, clinical manifestations, treatment, and outcome of a case with COVID-19 complicated by relapsing viral keratoconjunctivitis is described, and the involvement of topical cytokine surge in the pathogenesis of COVID-19 as it relates to viral keratoconjunctivitis is reported. […] The initial progression of conjunctivitis might have been related to the proliferation rate of SARS-CoV-2 in the conjunctival sac. […] Therefore, we speculate that the disease was not caused by the direct invasion and destruction of SARS-CoV-2, but rather „topical cytokine surge” caused by the autoimmune response. […] Therefore, we conclude that conjunctivitis or keratoconjunctivitis caused by SARS-CoV-2, especially the symptoms at late stages (7 days or later) of the infection, was not due to the local invasion and destruction of the virus; instead, it was due to cytokine surge. […] Our findings indicated that SARS-CoV-2 could induce viral conjunctivitis through an exogenous mechanism. […] At late stages of the disease, keratoconjunctivitis was aggravated and more widespread, which was related to cytokine surge.

• #26 Conjunctivitis | AAFP

  https://www.aafp.org/pubs/afp/issues/1998/0215/p735.html

  The meibomian glands are sebaceous glands that line the posterior lid margin behind the eyelashes. These glands secrete an important oily component of the tear film. When inflamed, the meibomian glands malfunction, producing chronic inflammation of the eyelid margins and the conjunctiva, as well as irritating dry-eye symptoms. This condition is referred to as meibomianitis. […] Ocular Chlamydia trachomatis infection can occur in two distinct clinical forms: trachoma (associated with serotypes A through C) and inclusion conjunctivitis (associated with serotypes D through K). […] Inclusion conjunctivitis is a common, primarily sexually transmitted disease that occurs in both newborns (ophthalmia neonatorum) and adults (adult inclusion conjunctivitis). It is the most frequent cause of conjunctivitis in neonates, followed, in order of decreasing prevalence, by infections with several bacteria species and, finally, N. gonorrhoeae. […] Adult inclusion conjunctivitis typically presents in young, sexually active persons between 18 and 30 years of age. Transmission most often occurs by autoinoculation from infected genital secretions.

• #27 Immunopathology of Allergic Conjunctivitis – European Medical Journal

  https://www.emjreviews.com/allergy-immunology/article/immunopathology-of-allergic-conjunctivitis/

  Environmental allergens possess proteolytic capabilities that cause damage to the epithelium; subsequently, damaged epithelial cells release pro-allergic cytokines, such as IL-33. […] TSLP is a pro-allergic cytokine released by allergen-activated conjunctival epithelium. […] Thus, Th2 cells and conjunctival epithelial cells participate in initiating priming of conjunctival mast cells in the sensitisation phase of allergic conjunctivitis. […] The early phase allergic response is initiated by the binding of multivalent allergens to the IgE-FcRI complex on primed conjunctival mast cells. […] Degranulation of mast cells results in immunobiological reactions that occur in response to the release of preformed mediators, such as biogenic amines (e.g., histamine) and neutral proteases (e.g., tryptase).

• #28 Immunopathology of Allergic Conjunctivitis – European Medical Journal

  https://www.emjreviews.com/allergy-immunology/article/immunopathology-of-allergic-conjunctivitis/

  The clinical manifestations of the early phase allergic reaction are attributed to the action of histamine on the vascular endothelium of conjunctival blood vessels, conjunctival sensory nerve fibres, immune cells, and resident cells in the conjunctiva and conjunctival epithelium. […] Additionally, degranulated mast cells release lipid mediators, such as prostaglandins and leukotrienes, which play a role in the early stages of the late phase allergic response and potentiate the histamine-mediated clinical expression of allergic conjunctivitis. […] Cytokines play a role in activating conjunctival epithelial cells and fibroblasts, as well as recruiting and activating eosinophils in the late phase. […] As such, conjunctival mast cell-derived cytokines and chemokines in conjunction with prostaglandins and leukotrienes contribute to the immunopathology of the late phase of allergic conjunctival inflammatory reaction.

• #29 Clinical Overview of Pink Eye (Conjunctivitis) | Conjunctivitis (Pink Eye) | CDC

  https://www.cdc.gov/conjunctivitis/hcp/clinical-overview/index.html

  Conjunctivitis is caused by viruses, bacteria, allergens, contact lens use, chemicals, fungi, and certain diseases. […] Viral conjunctivitis is very contagious and mostly spread through hand-to-eye contact by hands or objects that are contaminated with the virus. […] Bacterial conjunctivitis is very contagious and can spread from person to person in many ways. […] Alternatively, changes in the usual bacteria that live on the conjunctiva can also cause conjunctivitis. […] Signs and symptoms of bacterial conjunctivitis overlap with other causes of conjunctivitis, including viral and allergic conjunctivitis, which can make diagnosis difficult. […] Most cases of acute, infectious conjunctivitis in adults are viral and self-limited; these cases do not require antimicrobial treatment. Antiviral medication may be used to treat more serious forms of conjunctivitis. This can include conjunctivitis caused by herpes simplex virus or varicella-zoster virus. […] Contact lens wearers with bacterial conjunctivitis are at higher risk of bacterial keratitis. They should be asked to remove their contact lenses; treated with topical antibiotics; and promptly evaluated by an ophthalmologist.

• #30 Infective Conjunctivitis – Its Pathogenesis, Management and Complications | IntechOpen

  https://www.intechopen.com/chapters/44041

  The prognosis of bacterial conjunctivitis is normally very good with the correct and prompt treatment of the infection. In many cases, spontaneous remission, without a cure, is seen. In a study done by Sheikh and Hurwitz et al, spontaneous cure occurred in 60% of patients within 1-2 weeks. However, with prompt antibiotic treatment, the treatment time is significantly reduced. […] Much unlike bacterial conjunctivitis, there are many pathogens associated with viral conjunctivitis, although the majority of cases of viral conjunctivitis are encompassed by a few common pathogens. […] The key symptom of viral conjunctivitis is pink eye. This shows a fine, diffuse pinkness of the conjunctiva, which is often easily mistaken for the ciliary injection of iritis. Other symptoms associated with viral conjunctivitis include discharge which is often clear and watery. This is often the most discernible difference between bacterial and viral conjunctivitis. […] The most serious complication of viral conjunctivitis is herpes simplex keratitis, a corneal ulcer, which can ultimately lead to blindness. This is an extremely rare side effect of viral conjunctivitis and requires immediate transfer to hospital and review by the ophthalmologists.

• #31 Pathogenesis and management of adenoviral keratoconjunctivitis | IDR

  https://www.dovepress.com/pathogenesis-and-management-of-adenoviral-keratoconjunctivitis-peer-reviewed-fulltext-article-IDR

  Adenoviral tropism is related to affinity of host cellular receptors for fiber knob for viral entry and penton base for viral internalization. Binding affinity for host cellular receptors plays a role in viral tropism, with broadening of viral tropism linked to degree of binding affinity. […] The ocular manifestations of HAdV infections are widely variable. PCF is the most common presentation, primarily affecting children. […] EKC is the most severe form of ocular HAdV infection. […] The most unique characteristic of this type of conjunctivitis is its ability to gain entry into the cornea, resulting in a severe inflammatory response that often leads to detrimental visual disturbance. […] The presence of sight-threatening complications postocular adenoviral disease warrants the necessity of developing antiadenoviral therapy with enhanced therapeutic index and safety profile. As such, adenoviral genes and proteins involved in the process of adenoviral pathogenesis could serve as potential therapeutic targets for developing antiviral therapy.

• #32 Conjunctivitis | Description, Causes, Symptoms, & Treatment | Britannica

  https://www.britannica.com/science/conjunctivitis

  Bacterial invasion of the conjunctiva is less common than viral infection. Infection is through direct contact with an infected person or through a persons own nasal or sinus mucosa. […] The microorganisms most commonly responsible for bacterial conjunctivitis in humans are Staphylococcus, Streptococcus, and Haemophilus influenzae (which may invade the respiratory tract or the brain coverings). […] The microorganism Chlamydia trachomatis is responsible for trachoma, a disease in which the conjunctiva and cornea can become scarred, leading to blindness. […] Inclusion conjunctivitis, so called because of the small bodies that are observed within (included in) the infected cells, is also caused by C. trachomatis. […] Conjunctivitis frequently results from an allergic reaction to topical eye medications or to airborne allergens such as hay fever pollen. Prominent symptoms include eyelid swelling, itching, eye redness, and a stringy mucoid discharge.

• #33

  https://journals.lww.com/corneajrnl/fulltext/2019/08000/use_of_topical_steroids_in_conjunctivitis__a.26.aspx

  When used alone, topical steroid use is associated with prolonged periods of viral shedding and infection. The anti-inflammatory and immunosuppressive effect of corticosteroids is thought to inhibit normal viral clearance by the immune system. However, when used in combination with anti-infectives, corticosteroids such as dexamethasone have been shown to be well tolerated and efficacious in treating inflammatory conditions associated with viral and bacterial infections. […] Topical ophthalmic dexamethasone is routinely used to treat ocular inflammation. It is the most widely used corticosteroid in ophthalmology and has been studied extensively. […] The combination of PVP-I and dexamethasone has the potential to treat both viral and bacterial conjunctivitis and also to address the inflammatory component of infectious conjunctivitis.

• #34

  https://journals.lww.com/corneajrnl/fulltext/2019/08000/use_of_topical_steroids_in_conjunctivitis__a.26.aspx

  Conjunctivitis, or inflammation of the conjunctiva, is a common condition that can be caused by infectious (eg, bacterial or viral infections) and noninfectious (eg, allergy) etiologies. […] Topical corticosteroids are useful in treating ocular inflammation, but most treatment guidelines recommend steroid use generally in severe cases of conjunctivitis. This is partly due to risks associated with steroid use. These risks include potential for prolonging adenoviral infections and potentiating/worsening herpes simplex virus infections, increased intraocular pressure, glaucoma, and cataracts. […] Clinical data show that ophthalmic formulations that combine corticosteroids with broad-spectrum anti-infectives could be effective and well tolerated when used for short-term treatment (2 weeks).

• #35 Prevention and Treatment of Cytarabine-Induced Keratoconjunctivitis

  https://jhoponline.com/issue-archive/2015-issues/march-vol-5-no-1/16337:prevention-and-treatment-of-cytarabine-induced-keratoconjunctivitis

  Cytarabine has a known ability to penetrate body fluids, including crossing the bloodbrain barrier, and can be found in the aqueous humor and in tears. Corneal toxicity appears to be related to the concentration of cytarabine in tears, and the duration of exposure. Risk factors vary with high-dose cytarabine, and duration of dosing is most strongly associated with the toxicity; few cases have been seen with intermittent or continuously administered intravenous, low-dose cytarabine (eg, 200 mg/m2/day). Conjunctivitis has occurred as early as 3 days into therapy, and several days after therapy, with days 6 to 8 posttherapy the most commonly reported time of occurrence. […] The mechanism of microcyst formation is currently unknown. Corneal epithelial stem cells have a long cycle time and are unlikely to be cytarabine-susceptible; however, they bring about more differentiated transient amplifying cells in the basal layer, which divide more frequently and may therefore be vulnerable to cytarabine toxicity.

• #36 Prevention and Treatment of Cytarabine-Induced Keratoconjunctivitis

  https://jhoponline.com/issue-archive/2015-issues/march-vol-5-no-1/16337:prevention-and-treatment-of-cytarabine-induced-keratoconjunctivitis

  The mechanism of conjunctivitis prevention is unclear, but may rely on a decreased replication rate induced by corticosteroids impacting DNA replication in corneal cells. An additional mechanism of action may be a diluting effect on the cytarabine concentration; 1 trial showed benefits achieved from frequent use of artificial tears. […] Even though evidence has been reported that deoxycytidine, a competitive inhibitor of cytarabine, may be an effective antidote, a commercially available product for patient use is still not available.

• #37 Predominant role of Haemophilus influenzae in the association of conjunctivitis, acute otitis media and acute bacterial paranasal sinusitis in children | Scientific Reports

  https://www.nature.com/articles/s41598-020-79680-6

  To our knowledge, our study is the first report demonstrating the link among bacterial conjunctivitis, acute otitis media and acute bacterial paranasal sinusitis. […] These findings suggest that there may be a conjunctivitisotitis mediasinusitis syndrome that shares a same pathogenic process as conjunctivitisotitis media syndrome. […] Although the pathogenesis remains to be elucidated, we postulated that rhinitis caused by viral infection or allergic inflammation of the upper respiratory tract may lead to edema of the ostia of Eustachian tubes, nasolacrimal ducts and paranasal sinuses, resulting in obstruction and bacterial superinfection. […] Many H. influenzae strains may produce biofilm which leads to failure of antibiotic treatment and liability of recurrence. […] The present study shows an alarming high ampicillin resistance of 80%, and a high amoxicillin-clavulanate resistant rate of 18% for H. influenzae.

• #38

  https://ww-w.grantome.com/grant/NIH/R01-EY011901-01A1

  Conjunctivitis is the major atopic disease affecting the ocular surface. Indeed, it is one of the most commonly observed diseases in ophthalmic clinics. […] The design of new drugs require a better understanding of the pathophysiology and biogenesis of the disease. […] Previous data indicate that while the pathophysiology of atopic conjunctivitis resembles that of rhinitis and asthma, there are also important variables that determine whether allergic inflammation will occur in each, or only a subset of these disparate sites in a particular individual. […] The PI hypothesizes that there are particular gene products that specifically target the allergic response to the eye in patients with conjunctivitis, just as they are thought to be specific asthma-predisposing genes. […] The PI hopes that the identification of gene products involved in the pathogenesis of allergic conjunctivitis will permit the development of novel therapies for those afflicted with the disease and with other inflammatory diseases of the eye.

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