Materiały źródłowe

• #1 Ocular Rosacea: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/1197341-overview

  The precise pathophysiology of rosacea remains unclear but comprises both vascular dysregulation and altered immune system responses and inflammatory changes. Recent research has shown an upregulation of proinflammatory and vasoregulatory genes in rosacea patients. Alterations in the innate immune system responses include an overabundance of cathelicidin (an antimicrobial peptide), along with kallikrein-5, an enzyme involved in processing cathelicidin. Moreover, toll-like receptor 2 activity in the innate immune system is increased in patients with rosacea. […] A variety of rosacea triggers have been described including skin colonization with Demodex mites (along with bacteria in their gut) and Staphylococcus epidermidis. Eradication of Helicobacter pylori has been shown to improve rosacea in some patients, and the organism may play a role in the pathogenesis of inflammation in rosacea. […] Four distinct rosacea subtypes have been described: erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea.

• #2 Rosacea, the Eye, and the Gut – Modern Optometry

  https://modernod.com/articles/2022-nov-dec/rosacea-the-eye-and-the-gut

  Rosacea is a chronic inflammatory skin condition characterized by recurrent episodes of erythema, telangiectasia, papules, and pustules primarily affecting the central face and periocular regions. Its pathogenesis is hypothesized to be from a combination of immune system dysregulation, abnormal vascular and neurologic signaling, and dysbiosis of microorganisms leading to inflammation of the skin. […] Ocular involvement is said to be present in about 75% of rosacea patients, and 20% of these patients present with ocular involvement before skin manifestations. […] Additionally, Demodex mites can appear in increased density on the skin and eyelids of patients with rosacea. Demodex causes eyelid inflammation and can physically block the meibomian glands. They also serve as a vector for bacteria, such as Streptococci and Staphylococci, to enter deep into the glands.

• #3 Ocular Rosacea: An Updated Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11872267/

  Ocular rosacea is a chronic inflammatory disorder affecting the ocular surface, often associated with cutaneous rosacea. This review aims to explore its pathogenesis, treatment approaches, and future directions for management. […] Ocular rosacea involves dysregulation of the immune and neurovascular systems, with toll-like receptor activation and complement system involvement leading to chronic ocular surface inflammation. Alterations in the ocular microbiome have been implicated in disease progression. […] Ocular rosacea is believed to have similar underlying mechanisms to cutaneous rosacea, including innate immunity, inflammation, vascular dysfunction, and neurosensory abnormalities. […] The pathogenesis of ocular rosacea involves a complex interplay between the innate and adaptive immune systems, resulting in chronic ocular surface inflammation.

• #4

  https://link.springer.com/article/10.1007/s13555-020-00461-0

  Ocular involvement may be observed in more than 50% of rosacea patients. […] The pathogenesis and pathophysiology of rosacea are not fully understood, but immune dysfunction, Demodex infection, and exposure to ultraviolet radiation are considered to be contributing factors. […] The impact of topical benzyl benzoate (+crotamiton) treatment on Demodex densities and clinical symptoms of rosacea and demodicosis was assessed in a retrospective study with 394 patients (117 with rosacea and 277 with demodicosis), with similar results observed in both patient cohorts. […] Recent research has expanded the use of tranexamic acid in rosacea treatment. […] The pathogenesis of rosacea is not well understood. Immune dysfunction, Demodex, ultraviolet radiation exposure, and vascular hyperreactivity may all play a role in the pathogenesis of rosacea. […] The pathogenesis and related mechanisms need further exploration to develop more etiological treatment modalities.

• #5

  https://journals.lww.com/corneajrnl/fulltext/2025/04000/ocular_rosacea__an_updated_review.20.aspx

  The loss of homeostasis between the antiinflammatory and proinflammatory factors contributes to the vasodilation, vascular hyperreactivity, and disruption of the ocular surface integrity observed in ocular rosacea. […] The complex nature of ocular rosacea, with its interplay of immune, vascular, and neurosensory factors, underscores the need for a comprehensive approach to understanding and managing this condition as it presents a challenge in clinical practice. […] Recent studies have highlighted the potential significance of the ocular microbiome in the pathogenesis of ocular rosacea. […] The genetic basis of ocular rosacea remains uncertain, but emerging evidence suggests that genetic factors play a role in the development of and susceptibility to this condition. […] Ocular rosacea is characterized by vascular abnormalities, including vasodilation and telangiectasia, contributing to the characteristic erythema and flushing observed in this condition. […] The pathophysiologic mechanisms underlying the cutaneous and ocular manifestations of rosacea are likely shared as both conditions are characterized by altered innate immune responses, vascular dysfunction, and neurogenic inflammation.

• #6 Ocular Rosacea: An Updated Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11872267/

  Ocular rosacea is a chronic inflammatory disorder affecting the ocular surface, often associated with cutaneous rosacea. This review aims to explore its pathogenesis, treatment approaches, and future directions for management. […] Ocular rosacea involves dysregulation of the immune and neurovascular systems, with toll-like receptor activation and complement system involvement leading to chronic ocular surface inflammation. Alterations in the ocular microbiome have been implicated in disease progression. […] Ocular rosacea is believed to have similar underlying mechanisms to cutaneous rosacea, including innate immunity, inflammation, vascular dysfunction, and neurosensory abnormalities. […] The pathogenesis of ocular rosacea involves a complex interplay between the innate and adaptive immune systems, resulting in chronic ocular surface inflammation.

• #7

  https://journals.lww.com/corneajrnl/fulltext/2025/04000/ocular_rosacea__an_updated_review.20.aspx

  Ocular rosacea is a chronic inflammatory disorder affecting the ocular surface, often associated with cutaneous rosacea. […] Ocular rosacea involves dysregulation of the immune and neurovascular systems, with toll-like receptor activation and complement system involvement leading to chronic ocular surface inflammation. […] Emerging evidence suggests that ocular and facial microbiome alterations may be crucial in the development and perpetuation of ocular rosacea. […] Ocular rosacea is characterized by immune system dysfunction. Rosacea seems to cause an excessive activation of the innate immune system, specifically toll-like receptors (TLRs) and the complement system. […] The pathogenesis of ocular rosacea involves a complex interplay between the innate and adaptive immune systems, resulting in chronic ocular surface inflammation.

• #8 Ocular Rosacea: An Updated Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11872267/

  Ocular rosacea is characterized by immune system dysfunction. Rosacea seems to cause an excessive activation of the innate immune system, specifically toll-like receptors (TLRs) and the complement system. […] The pathogenesis of ocular rosacea involves a complex interplay between the innate and adaptive immune systems, resulting in chronic ocular surface inflammation. […] The genetic basis of ocular rosacea remains uncertain, but emerging evidence suggests that genetic factors play a role in the development of and susceptibility to this condition. […] Ocular rosacea is characterized by vascular abnormalities, including vasodilation and telangiectasia, contributing to the characteristic erythema and flushing observed in this condition. […] The complex nature of ocular rosacea, with its interplay of immune, vascular, and neurosensory factors, underscores the need for a comprehensive approach to understanding and managing this condition as it presents a challenge in clinical practice.

• #9 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/?lang=en

  Additionally, local proteases (serine protease KLK5) that control the production of cathelicidin in epidermis were also abnormally expressed in rosacea patients. To further test their hypothesis, researchers injected abnormal cathelicidin or protease that produce these peptides in the skin of mice and observed similar inflammatory features of the disease found in humans. […] Observation of higher amounts of receptors of the recognition system, Toll-like receptor 2 (TLR2), in the epidermis of patients with rosacea explained the overreaction of these patients to environmental stimuli, since enhanced action of TLR2 in keratinocytes leads to an increase in serine protease KLK5 and cathelicidin production. […] Interestingly, tetracyclines, which improve signs and symptoms of rosacea, are known to inhibit expression and activity of several matrix metalloproteinases, as well as a class of proteases that activate cathelicidin, sustaining this theory.

• #10 Rosacea: Symptoms, Causes, and Management – DermNet

  https://dermnetnz.org/topics/rosacea

  The pathogenesis of rosacea is thought to be multifactorial and includes: […] Dysregulation of the immune response may lead to excessive inflammation, vasodilation, lymphatic dilatation, and angiogenesis. […] In the skin of patients with rosacea, there is increased expression and activity of toll-like receptor 2, cathelicidins, kallikrein 5, and mast cells. […] The result is an exaggerated innate immune reaction to the initial trigger. […] Increased Th17 expression can increase levels of cathelicidin LL-37 in keratinocytes and drive further inflammation. […] The most significant environmental trigger is UV radiation; affected skin is more sensitive to exposure. UV radiation can damage the dermis and increase skin inflammation. […] Ocular rosacea (lid margin telangiectasia, blepharitis, keratitis/conjunctivitis/sclerokeratitis/anterior uveitis). […] General management […] First-line medical management […] If severe: azithromycin, doxycycline.

• #11 Advances in the Pathogenesis and Treatment of Rosacea: A Phenotype-Based Therapeutic Approach

  https://www.mdpi.com/2079-9284/11/1/11

  Rosacea is a common chronic inflammatory skin disorder that mainly affects the central face. Its pathogenesis is complex and still not completely understood. It encompasses innate and adaptive immune system dysregulation, neurovascular dysfunction, and genetic and environmental factors. […] Although the real nature of rosacea remains largely elusive, it is known that its pathogenesis encompasses a complex interplay between innate and adaptive immune system dysregulation, neurovascular dysfunction, and genetic and environmental factors. […] The dysregulation of toll-like receptor (TLR)2-kallikrein (KLK5)-cathelicidin(LL37) pathways has a crucial role in the pathogenesis of rosacea. […] The complex immunomodulatory role of LL-37 is driven by multiple pathways. […] Interestingly, LL-37 activates the Janus kinase (JAK)/signal transducer and transcription activator (STAT) signaling pathway, which mediates monocyte chemotaxis and IL-6-, IL-8-, and TNFα expression.

• #12 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/?lang=en

  Cathelicidin, one of these antimicrobial peptides, has both vasoactive and pro-inflammatory actions and is implicated in the pathogenesis of this disorder. Based on the observation of a single molecule that presents both vasoactive and pro-inflammatory actions, researchers decided to study the behavior of such molecule in rosacea. As hypothesized, these peptides were found in greater levels in the skin of individuals with rosacea than in normal facial skin. […] Moreover, the cathelicidin peptides found in rosacea patients were not only more abundant but were different from those found in normal individuals. These forms of cathelicidin peptides are known for its role in natural host defense against infections and in promoting leukocyte chemotaxis, angiogenesis, and extracellular matrix component expression. Supporting this theory, gene array studies found that mRNA expression levels of cathelicidin were found to be significantly increased in all subtypes of rosacea.

• #13 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/?lang=en

  Cathelicidin, one of these antimicrobial peptides, has both vasoactive and pro-inflammatory actions and is implicated in the pathogenesis of this disorder. Based on the observation of a single molecule that presents both vasoactive and pro-inflammatory actions, researchers decided to study the behavior of such molecule in rosacea. As hypothesized, these peptides were found in greater levels in the skin of individuals with rosacea than in normal facial skin. […] Moreover, the cathelicidin peptides found in rosacea patients were not only more abundant but were different from those found in normal individuals. These forms of cathelicidin peptides are known for its role in natural host defense against infections and in promoting leukocyte chemotaxis, angiogenesis, and extracellular matrix component expression. Supporting this theory, gene array studies found that mRNA expression levels of cathelicidin were found to be significantly increased in all subtypes of rosacea.

• #14 Ocular Rosacea—a Review – touchOPHTHALMOLOGY

  https://touchophthalmology.com/ocular-immunology/journal-articles/ocular-rosacea-a-review/

  Ocular rosacea is a chronic inflammatory disorder which may present in various manifestations such as chronic blepharoconjunctivitis, meibomian gland dysfunction, corneal vascularization, infiltration, scarring and, albeit rarely, even perforation. […] The exact etiology and pathogenesis of rosacea has not yet been clearly defined, however, based on the spectrum of clinical findings, various hypotheses have been suggested. These include the following. […] Rosacea is considered to be an inflammatory disorder. Cathelicidins, a family of antimicrobial peptides involved in innate and adaptive immune response have been found in higher levels in rosacea affected skin, with cathelicidin LL-37 in particular being implicated in the pathogenesis. […] Despite these mediators having been identified, the primary initiating mechanism for inflammation is still not clear.

• #15 Ocular Rosacea – EyeWiki

  https://eyewiki.org/Ocular_Rosacea

  Cathelicidin in turn causes an increase in the vascular endothelial growth factor (VEGF) level in epidermal keratinocytes leading to vascular endothelial changes and angiogenesis. […] Additional sources of inflammation include elevated levels of interleukin-1a and b, gelatinase B (metalloproteinase-9) and collagenase-2 (MMP-8) in the tear fluids of patients with ocular rosacea. […] Elevated serum level of Tumor necrosis factor (TNF-alfa) and overexpression of ICAM-1 (intercellular adhesion molecule 1) and HLA-DR in conjunctival epithelial cells of these patients is also observed.

• #16 Advances in the Pathogenesis and Treatment of Rosacea: A Phenotype-Based Therapeutic Approach

  https://www.mdpi.com/2079-9284/11/1/11

  Rosacea is a common chronic inflammatory skin disorder that mainly affects the central face. Its pathogenesis is complex and still not completely understood. It encompasses innate and adaptive immune system dysregulation, neurovascular dysfunction, and genetic and environmental factors. […] Although the real nature of rosacea remains largely elusive, it is known that its pathogenesis encompasses a complex interplay between innate and adaptive immune system dysregulation, neurovascular dysfunction, and genetic and environmental factors. […] The dysregulation of toll-like receptor (TLR)2-kallikrein (KLK5)-cathelicidin(LL37) pathways has a crucial role in the pathogenesis of rosacea. […] The complex immunomodulatory role of LL-37 is driven by multiple pathways. […] Interestingly, LL-37 activates the Janus kinase (JAK)/signal transducer and transcription activator (STAT) signaling pathway, which mediates monocyte chemotaxis and IL-6-, IL-8-, and TNFα expression.

• #17 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/?lang=en

  Additionally, local proteases (serine protease KLK5) that control the production of cathelicidin in epidermis were also abnormally expressed in rosacea patients. To further test their hypothesis, researchers injected abnormal cathelicidin or protease that produce these peptides in the skin of mice and observed similar inflammatory features of the disease found in humans. […] Observation of higher amounts of receptors of the recognition system, Toll-like receptor 2 (TLR2), in the epidermis of patients with rosacea explained the overreaction of these patients to environmental stimuli, since enhanced action of TLR2 in keratinocytes leads to an increase in serine protease KLK5 and cathelicidin production. […] Interestingly, tetracyclines, which improve signs and symptoms of rosacea, are known to inhibit expression and activity of several matrix metalloproteinases, as well as a class of proteases that activate cathelicidin, sustaining this theory.

• #18 Molecular Vision: Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models

  http://www.molvis.org/molvis/v27/323/

  Overall, all these phenomena in the skin and eye act in synergy to maintain chronic inflammation at the cutaneous, epidermal, conjunctival, and perivascular interface, eventually leading to secondary fibrosis. […] TLR-2 can also activate the NLRP3 inflammasome and induce cell death. […] In tears, rosacea patients have increased levels of IL-1, IL-1, IL-16, TNF-, monocyte chemoattractant protein-1 (MCP-1), MMP-8, and MMP-9. […] The link between LL-37 and rosacea was demonstrated by Yamasaki et al. in an inflammatory skin mouse model induced by the injection of LL-37, developing telangiectasia, erythema, and inflammation. […] The role of mast cells was further confirmed when LL-37 injection in mice knocked out for mast cells did not develop any phenotype. […] However, few of the conducted studies have been performed in the eye, and there is no clear evidence implicating LL-37 in ocular rosacea.

• #19 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/

  The precise etiology and pathophysiologic mechanisms of cutaneous and ocular rosacea remain unknown, although different theories have been proposed. Several studies confirm the inflammatory nature of the disease. An elevated concentration of interleukin-1a and b and a greater activity of gelatinase B (metalloproteinase -9) and colagenase-2 (MMP-8) have been found in tear fluids of patients with ocular rosacea. Doxycycline, used in the treatment of cutaneous and ocular rosacea, decreases both MMP-8 and MMP-9 activity. Tumor necrosis factor (TNF-alfa) was also elevated in rosacea. Significant overexpression of ICAM-1 (intercellular adhesion molecule 1) and HLA-DR, inflammatory markers, was observed in conjunctival epithelial cells of patients with rosacea. […] Recently, studies have shown that disease exacerbation is stimulated by normal external environmental factors, leading to unique activation of pro-inflammatory systems as well as innate immune responses. Molecular studies propose that the enhanced sensitivity of patients with rosacea may be caused by abnormal recognition of common environmental stimuli. Factors that trigger the innate immune system lead to an increase in the expression of certain cytokines and anti-microbial molecules in the skin. Cathelicidin, one of these antimicrobial peptides, has both vasoactive and pro-inflammatory actions and is implicated in the pathogenesis of this disorder.

• #20 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/?lang=en

  The precise etiology and pathophysiologic mechanisms of cutaneous and ocular rosacea remain unknown, although different theories have been proposed. Several studies confirm the inflammatory nature of the disease. An elevated concentration of interleukin-1a and b and a greater activity of gelatinase B (metalloproteinase -9) and colagenase-2 (MMP-8) have been found in tear fluids of patients with ocular rosacea. Doxycycline, used in the treatment of cutaneous and ocular rosacea, decreases both MMP-8 and MMP-9 activity. Tumor necrosis factor (TNF-alfa) was also elevated in rosacea. Significant overexpression of ICAM-1 (intercellular adhesion molecule 1) and HLA-DR, inflammatory markers, was observed in conjunctival epithelial cells of patients with rosacea. […] Recently, studies have shown that disease exacerbation is stimulated by normal external environmental factors, leading to unique activation of pro-inflammatory systems as well as innate immune responses. Molecular studies propose that the enhanced sensitivity of patients with rosacea may be caused by abnormal recognition of common environmental stimuli. Factors that trigger the innate immune system lead to an increase in the expression of certain cytokines and anti-microbial molecules in the skin.

• #21 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/

  The precise etiology and pathophysiologic mechanisms of cutaneous and ocular rosacea remain unknown, although different theories have been proposed. Several studies confirm the inflammatory nature of the disease. An elevated concentration of interleukin-1a and b and a greater activity of gelatinase B (metalloproteinase -9) and colagenase-2 (MMP-8) have been found in tear fluids of patients with ocular rosacea. Doxycycline, used in the treatment of cutaneous and ocular rosacea, decreases both MMP-8 and MMP-9 activity. Tumor necrosis factor (TNF-alfa) was also elevated in rosacea. Significant overexpression of ICAM-1 (intercellular adhesion molecule 1) and HLA-DR, inflammatory markers, was observed in conjunctival epithelial cells of patients with rosacea. […] Recently, studies have shown that disease exacerbation is stimulated by normal external environmental factors, leading to unique activation of pro-inflammatory systems as well as innate immune responses. Molecular studies propose that the enhanced sensitivity of patients with rosacea may be caused by abnormal recognition of common environmental stimuli. Factors that trigger the innate immune system lead to an increase in the expression of certain cytokines and anti-microbial molecules in the skin. Cathelicidin, one of these antimicrobial peptides, has both vasoactive and pro-inflammatory actions and is implicated in the pathogenesis of this disorder.

• #22 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/

  Supporting this theory, gene array studies found that mRNA expression levels of cathelicidin were found to be significantly increased in all subtypes of rosacea. Additionally, local proteases (serine protease KLK5) that control the production of cathelicidin in epidermis were also abnormally expressed in rosacea patients. […] Observation of higher amounts of receptors of the recognition system, Toll-like receptor 2 (TLR2), in the epidermis of patients with rosacea explained the overreaction of these patients to environmental stimuli, since enhanced action of TLR2 in keratinocytes leads to an increase in serine protease KLK5 and cathelicidin production. […] Furthermore, a recent study found elevated concentrations of 5 molecules involved in the innate immune response (interleukin-1b, interleukin-16, stem cell factor, monocyte chemotactic protein (MCP)-1, and monokine induced by g-interferon) in cutaneous biopsy specimens taken from ocular rosacea patients, supporting the concept that ocular rosacea is a disorder of innate immunity.

• #23 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/?lang=en

  Furthermore, a recent study found elevated concentrations of 5 molecules involved in the innate immune response (interleukin-1b, interleukin-16, stem cell factor, monocyte chemotactic protein (MCP)-1, and monokine induced by g-interferon) in cutaneous biopsy specimens taken from ocular rosacea patients, supporting the concept that ocular rosacea is a disorder of innate immunity.

• #24 Eyelid Protein Reveals Rosacea Pathogenesis

  https://www.reviewofoptometry.com/article/eyelid-protein-reveals-rosacea-pathogenesis

  Rosacea is a common condition among the US population, affecting as much as 10% of the population. […] Research shows as many as 58% to 72% of rosacea patients have ocular involvement, and 45% to 85% have ocular complaints. […] New research from the Lions Eye Institute in New York used eyelid specimens from patients with rosacea to discovered increased amounts of the protein nuclear factor kappa-B (NFKB), which may have implications for treatment one day. […] The activated form of NFKB is enriched in rosacea, indicating a role for this pathway in the pathogenesis of this disease. […] Interference with NFKB signaling may represent a novel therapy for rosacea as clinical agents become available, the study concludes.

• #25 Eyelid Protein Reveals Rosacea Pathogenesis

  https://www.reviewofoptometry.com/article/eyelid-protein-reveals-rosacea-pathogenesis

  Rosacea is a common condition among the US population, affecting as much as 10% of the population. […] Research shows as many as 58% to 72% of rosacea patients have ocular involvement, and 45% to 85% have ocular complaints. […] New research from the Lions Eye Institute in New York used eyelid specimens from patients with rosacea to discovered increased amounts of the protein nuclear factor kappa-B (NFKB), which may have implications for treatment one day. […] The activated form of NFKB is enriched in rosacea, indicating a role for this pathway in the pathogenesis of this disease. […] Interference with NFKB signaling may represent a novel therapy for rosacea as clinical agents become available, the study concludes.

• #26

  https://journals.lww.com/corneajrnl/fulltext/2025/04000/ocular_rosacea__an_updated_review.20.aspx

  The loss of homeostasis between the antiinflammatory and proinflammatory factors contributes to the vasodilation, vascular hyperreactivity, and disruption of the ocular surface integrity observed in ocular rosacea. […] The complex nature of ocular rosacea, with its interplay of immune, vascular, and neurosensory factors, underscores the need for a comprehensive approach to understanding and managing this condition as it presents a challenge in clinical practice. […] Recent studies have highlighted the potential significance of the ocular microbiome in the pathogenesis of ocular rosacea. […] The genetic basis of ocular rosacea remains uncertain, but emerging evidence suggests that genetic factors play a role in the development of and susceptibility to this condition. […] Ocular rosacea is characterized by vascular abnormalities, including vasodilation and telangiectasia, contributing to the characteristic erythema and flushing observed in this condition. […] The pathophysiologic mechanisms underlying the cutaneous and ocular manifestations of rosacea are likely shared as both conditions are characterized by altered innate immune responses, vascular dysfunction, and neurogenic inflammation.

• #27 Ocular Rosacea: An Updated Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11872267/

  Ocular rosacea is characterized by immune system dysfunction. Rosacea seems to cause an excessive activation of the innate immune system, specifically toll-like receptors (TLRs) and the complement system. […] The pathogenesis of ocular rosacea involves a complex interplay between the innate and adaptive immune systems, resulting in chronic ocular surface inflammation. […] The genetic basis of ocular rosacea remains uncertain, but emerging evidence suggests that genetic factors play a role in the development of and susceptibility to this condition. […] Ocular rosacea is characterized by vascular abnormalities, including vasodilation and telangiectasia, contributing to the characteristic erythema and flushing observed in this condition. […] The complex nature of ocular rosacea, with its interplay of immune, vascular, and neurosensory factors, underscores the need for a comprehensive approach to understanding and managing this condition as it presents a challenge in clinical practice.

• #28 Advances in the Pathogenesis and Treatment of Rosacea: A Phenotype-Based Therapeutic Approach

  https://www.mdpi.com/2079-9284/11/1/11

  Comprehensively, increased skin blood flow, angiogenesis, and vasodilatation are essential processes in rosacea, as demonstrated by typical clinical features such as facial erythema and flushing. […] The proximity between immune cells in the skin barrier and peripheral nervous system nerves may partially explain the intensive bidirectional crosstalk between those systems through different mediators. […] The sebaceous glands are exocrine glands that produce sebum, a lipid-rich fluid, produced by the holocrine rupture of mature sebocytes and secreted onto the surface of the skin. […] The dryness and hypersensitivity of rosacea skin may be attributed to a reduction in the hydration of the stratum corneous, also due to the decrease in claudin expression, a tight junction membrane protein which forms paracellular barriers and pores, determining tight junction permeability.

• #29

  https://journals.lww.com/corneajrnl/fulltext/2025/04000/ocular_rosacea__an_updated_review.20.aspx

  The loss of homeostasis between the antiinflammatory and proinflammatory factors contributes to the vasodilation, vascular hyperreactivity, and disruption of the ocular surface integrity observed in ocular rosacea. […] The complex nature of ocular rosacea, with its interplay of immune, vascular, and neurosensory factors, underscores the need for a comprehensive approach to understanding and managing this condition as it presents a challenge in clinical practice. […] Recent studies have highlighted the potential significance of the ocular microbiome in the pathogenesis of ocular rosacea. […] The genetic basis of ocular rosacea remains uncertain, but emerging evidence suggests that genetic factors play a role in the development of and susceptibility to this condition. […] Ocular rosacea is characterized by vascular abnormalities, including vasodilation and telangiectasia, contributing to the characteristic erythema and flushing observed in this condition. […] The pathophysiologic mechanisms underlying the cutaneous and ocular manifestations of rosacea are likely shared as both conditions are characterized by altered innate immune responses, vascular dysfunction, and neurogenic inflammation.

• #30 Seeing Red: How Ocular Rosacea Impacts the Cornea

  https://www.reviewofoptometry.com/article/seeing-red-how-ocular-rosacea-impacts-the-cornea

  Chronic inflammation causes atrophy of the meibomian glands themselves, decreasing meibum production. […] Ocular rosacea patients also characteristically have an increased eyelid margin density of Demodex. […] An immune response to Demodex infestation on eyelash follicles and within meibomian glands also appears to contribute to chronic eyelid and meibomian gland inflammation and dysfunction. […] Inflammation causes corneal epithelial cells to produce fibroblast growth factors and pro-angiogenic factors such as vascular endothelial growth factor (VEGF). […] In response, conjunctival endothelial cells produce more MMPs, and the limbal epithelial cells, which are capable of producing neovascularization and opacification, migrate beyond their normal limbal location onto the cornea. […] This all contributes to triggering angiogenesis and corneal neovascularization.

• #31 Seeing Red: How Ocular Rosacea Impacts the Cornea

  https://www.reviewofoptometry.com/article/seeing-red-how-ocular-rosacea-impacts-the-cornea

  Chronic inflammation causes atrophy of the meibomian glands themselves, decreasing meibum production. […] Ocular rosacea patients also characteristically have an increased eyelid margin density of Demodex. […] An immune response to Demodex infestation on eyelash follicles and within meibomian glands also appears to contribute to chronic eyelid and meibomian gland inflammation and dysfunction. […] Inflammation causes corneal epithelial cells to produce fibroblast growth factors and pro-angiogenic factors such as vascular endothelial growth factor (VEGF). […] In response, conjunctival endothelial cells produce more MMPs, and the limbal epithelial cells, which are capable of producing neovascularization and opacification, migrate beyond their normal limbal location onto the cornea. […] This all contributes to triggering angiogenesis and corneal neovascularization.

• #32 Ocular Rosacea—a Review – touchOPHTHALMOLOGY

  https://touchophthalmology.com/ocular-immunology/journal-articles/ocular-rosacea-a-review/

  Demodex folliculorum mites have been found in higher densities in skin scrapings or superficial standardized skin biopsies of patients with rosacea, and a decrease in mite density after treatment has been reported. […] It is likely that an underlying genetic predisposition becomes manifest on exposure to environmental factors. Gene dysregulation may also be responsible for the derangement in inflammatory mediators and/or instability of the neurovascular component.

• #33 Seeing Red: How Ocular Rosacea Impacts the Cornea

  https://www.reviewofoptometry.com/article/seeing-red-how-ocular-rosacea-impacts-the-cornea

  Chronic inflammation causes atrophy of the meibomian glands themselves, decreasing meibum production. […] Ocular rosacea patients also characteristically have an increased eyelid margin density of Demodex. […] An immune response to Demodex infestation on eyelash follicles and within meibomian glands also appears to contribute to chronic eyelid and meibomian gland inflammation and dysfunction. […] Inflammation causes corneal epithelial cells to produce fibroblast growth factors and pro-angiogenic factors such as vascular endothelial growth factor (VEGF). […] In response, conjunctival endothelial cells produce more MMPs, and the limbal epithelial cells, which are capable of producing neovascularization and opacification, migrate beyond their normal limbal location onto the cornea. […] This all contributes to triggering angiogenesis and corneal neovascularization.

• #34 Seeing Red: How Ocular Rosacea Impacts the Cornea

  https://www.reviewofoptometry.com/article/seeing-red-how-ocular-rosacea-impacts-the-cornea

  Chronic inflammation causes atrophy of the meibomian glands themselves, decreasing meibum production. […] Ocular rosacea patients also characteristically have an increased eyelid margin density of Demodex. […] An immune response to Demodex infestation on eyelash follicles and within meibomian glands also appears to contribute to chronic eyelid and meibomian gland inflammation and dysfunction. […] Inflammation causes corneal epithelial cells to produce fibroblast growth factors and pro-angiogenic factors such as vascular endothelial growth factor (VEGF). […] In response, conjunctival endothelial cells produce more MMPs, and the limbal epithelial cells, which are capable of producing neovascularization and opacification, migrate beyond their normal limbal location onto the cornea. […] This all contributes to triggering angiogenesis and corneal neovascularization.

• #35 Rosacea

  https://www.racgp.org.au/afp/2017/may/rosacea

  Ocular manifestations of rosacea often precede the development of cutaneous signs, but can also occur concurrently. Ocular rosacea primarily affects adults, but occasionally may also affect children. It can affect males and females alike. Blepharitis and conjunctivitis are the most common findings. In some cases, ocular rosacea may also be associated with corneal damage. In severe cases, assessment by an ophthalmologist is recommended. […] The aetiology of rosacea comprises a number of factors, which are detailed below. Often, these factors overlap. […] An association between Demodex follicularum and rosacea has been reported. D. follicularum is a mite that lives in sebaceous follicles. In vitro investigations have found that D. follicularum has antigens that react with sera from patients with rosacea, and are capable of stimulating mononuclear cells to proliferate.

• #36 Rosacea and the Microbiome: A Systematic Review | springermedizin.de

  https://www.springermedizin.de/rosacea-and-the-microbiome-a-systematic-review/18572828

  Rosacea, a chronic inflammatory skin disease characterized by recurrent episodes of facial flushing, erythema, pustules, and telangiectasia, largely affects fair-skinned women over 30 years of age. […] Current theories highlight the role of the cutaneous microbiome and its associated inflammatory effects in rosacea’s pathogenesis. […] Importantly, the generation of reactive oxygen species (ROS) due to an altered innate immune response appears to be a component of rosacea’s mechanism of disease, as studies have demonstrated higher levels of ROS in patients with this condition. […] Several microorganisms including Demodex folliculorum, Bacillus oleronius, Staphylococcus epidermidis, and Cutibacterium acnes have been studied as potential players in rosacea’s pathogenesis. […] These microorganisms’ abnormal activation of the innate immune system via Toll-like receptor 2 has been extensively investigated.

• #37 Rosacea and the Microbiome: A Systematic Review | springermedizin.de

  https://www.springermedizin.de/rosacea-and-the-microbiome-a-systematic-review/18572828

  Rosacea, a chronic inflammatory skin disease characterized by recurrent episodes of facial flushing, erythema, pustules, and telangiectasia, largely affects fair-skinned women over 30 years of age. […] Current theories highlight the role of the cutaneous microbiome and its associated inflammatory effects in rosacea’s pathogenesis. […] Importantly, the generation of reactive oxygen species (ROS) due to an altered innate immune response appears to be a component of rosacea’s mechanism of disease, as studies have demonstrated higher levels of ROS in patients with this condition. […] Several microorganisms including Demodex folliculorum, Bacillus oleronius, Staphylococcus epidermidis, and Cutibacterium acnes have been studied as potential players in rosacea’s pathogenesis. […] These microorganisms’ abnormal activation of the innate immune system via Toll-like receptor 2 has been extensively investigated.

• #38 Ocular Rosacea | IntechOpen

  https://www.intechopen.com/chapters/53160

  Demodex folliculorum is a saprophytic mite that is found in normal flora of the skin. There are studies demonstrating that the Demodex density increased in rosacea patients. […] Bacillus olenorium serum immunoreactivity was detected in ocular rosacea patients. Its proteins cause high immune reactions. […] Staphylococcus epidermidis and Propionibacterium acnes that are found commonly in lid flora are accused microorganisms for their production of high levels of bacterial lipases. […] OR was found to be associated with the increased tear fluid levels of several inflammatory mediators such as interleukin-1 (IL-1) and gelatinase B activity. […] The meibomian glands of rosacea patients cause keratinization of epithelial cells, end up with thickening of secretions, plugging of the orifices, and trapping of the secretions.

• #39 An Analysis of the Role of Bacillus oleronius Proteins in the Pathogenesis of Ocular Rosacea – MURAL – Maynooth University Research Archive Library

  https://mural.maynoothuniversity.ie/id/eprint/7085/

  Rosacea is a chronic dermatosis of the central T-zone of the face and eyes. […] The aim of the work presented here was to investigate the role of a bacterium, Bacillus oleronius, in the pathogenesis of this disfiguring disease. […] It was previously established that B. oleronius produces two immunogenic proteins that are capable of inducing an immune response in rosacea patients. […] The expression of the immuno-reactive 62 kDa GroEL protein was analysed in different culture conditions to determine a possible role in the pathogenesis of the disease, and it was observed that the B. oleronius increased expression of the 62 kDa GroEL protein in response to stress following alterations in temperature, pH, reactive oxygen species (ROS) presence, and oxygen availability of the local environment.

• #40 Ocular Rosacea | IntechOpen

  https://www.intechopen.com/chapters/53160

  Demodex folliculorum is a saprophytic mite that is found in normal flora of the skin. There are studies demonstrating that the Demodex density increased in rosacea patients. […] Bacillus olenorium serum immunoreactivity was detected in ocular rosacea patients. Its proteins cause high immune reactions. […] Staphylococcus epidermidis and Propionibacterium acnes that are found commonly in lid flora are accused microorganisms for their production of high levels of bacterial lipases. […] OR was found to be associated with the increased tear fluid levels of several inflammatory mediators such as interleukin-1 (IL-1) and gelatinase B activity. […] The meibomian glands of rosacea patients cause keratinization of epithelial cells, end up with thickening of secretions, plugging of the orifices, and trapping of the secretions.

• #41 Seeing Red: How Ocular Rosacea Impacts the Cornea

  https://www.reviewofoptometry.com/article/seeing-red-how-ocular-rosacea-impacts-the-cornea

  Ocular rosacea is readily associated with blepharitis, eyelid margin telangiectasias, meibomian gland dysfunction and symptoms associated with dryness. […] Researchers have proposed many theories regarding the pathogenesis of rosacea, though none have been confirmed. The prevailing wisdom points to a mix of vascular and immunologic dysfunction. […] An increase in bacterial eyelid flora appears to have a strong contributory effect on ocular manifestations. […] Bacteria produce several lipolytic exoenzymes including cholesteryl esterase, triglyceride lipase and fatty wax esterase that act on the lipid-based meibum by hydrolyzing its sterol esters and wax, thus increasing glycerides and free fatty acids. […] This process also alters the meibum’s solubility, causing it to thicken. […] Inadequate and solidified meibum destabilizes the lipid layer of the tear film, allowing the aqueous to evaporate more quickly, increasing tear osmolarity and stimulating the inflammatory cascade.

• #42 Seeing Red: How Ocular Rosacea Impacts the Cornea

  https://www.reviewofoptometry.com/article/seeing-red-how-ocular-rosacea-impacts-the-cornea

  Ocular rosacea is readily associated with blepharitis, eyelid margin telangiectasias, meibomian gland dysfunction and symptoms associated with dryness. […] Researchers have proposed many theories regarding the pathogenesis of rosacea, though none have been confirmed. The prevailing wisdom points to a mix of vascular and immunologic dysfunction. […] An increase in bacterial eyelid flora appears to have a strong contributory effect on ocular manifestations. […] Bacteria produce several lipolytic exoenzymes including cholesteryl esterase, triglyceride lipase and fatty wax esterase that act on the lipid-based meibum by hydrolyzing its sterol esters and wax, thus increasing glycerides and free fatty acids. […] This process also alters the meibum’s solubility, causing it to thicken. […] Inadequate and solidified meibum destabilizes the lipid layer of the tear film, allowing the aqueous to evaporate more quickly, increasing tear osmolarity and stimulating the inflammatory cascade.

• #43 Molecular Vision: Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models

  http://www.molvis.org/molvis/v27/323/

  Rosacea is a multifactorial disease triggered by favoring factors, the pathogenesis of which remains imperfectly understood. […] The mechanisms of rosacea are still unclear. In recent years, a multifactorial pathogenesis with genetic predisposition has been emphasized. […] The infiltration of mast cells and the release of proinflammatory mediators, such as interleukin-1 (IL-1), IL-6, IL-17, interferon- (IFN-), matrix metalloproteinase-2 (MMP-2), MMP-9, tumor necrosis factor- (TNF-), activated by nuclear factor-B (NF-B), contribute to the inflammatory signs. […] Finally, the molecular steps involved in the pathogenesis of ocular rosacea are not fully known. Meibomian gland dysfunction has been recognized as a major component. […] A link between Demodex infestation and ocular rosacea has also been advocated.

• #44 Molecular Vision: Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models

  http://www.molvis.org/molvis/v27/323/

  The increase in cathelicidin levels in rosacea patients could be amplified via the expression of the protease-activated receptor 2 (PAR-2), which is activated by KLK-5 and known to mediate inflammation in various tissues, including the skin. […] The meibomian glands are sebaceous glands located in the epidermis of the lower and upper eyelids, which secrete meibum, a source of tear lipids. […] One of the main eye signs of ocular rosacea is MGD, as observed in several previous studies. […] The proinflammatory factors secondary to MGD cause inflammatory signs in eyelid edges. […] The mechanisms underlying the development of erythema in animals have not been approved as exactly mimicking those seen in humans with erythema associated with rosacea. […] Despite major advances in understanding the pathophysiology of cutaneous and ocular rosacea, the exact mechanisms are still poorly understood.

• #45 Ocular Rosacea | IntechOpen

  https://www.intechopen.com/chapters/53160

  Demodex folliculorum is a saprophytic mite that is found in normal flora of the skin. There are studies demonstrating that the Demodex density increased in rosacea patients. […] Bacillus olenorium serum immunoreactivity was detected in ocular rosacea patients. Its proteins cause high immune reactions. […] Staphylococcus epidermidis and Propionibacterium acnes that are found commonly in lid flora are accused microorganisms for their production of high levels of bacterial lipases. […] OR was found to be associated with the increased tear fluid levels of several inflammatory mediators such as interleukin-1 (IL-1) and gelatinase B activity. […] The meibomian glands of rosacea patients cause keratinization of epithelial cells, end up with thickening of secretions, plugging of the orifices, and trapping of the secretions.

• #46 Seeing Red: How Ocular Rosacea Impacts the Cornea

  https://www.reviewofoptometry.com/article/seeing-red-how-ocular-rosacea-impacts-the-cornea

  Chronic inflammation causes atrophy of the meibomian glands themselves, decreasing meibum production. […] Ocular rosacea patients also characteristically have an increased eyelid margin density of Demodex. […] An immune response to Demodex infestation on eyelash follicles and within meibomian glands also appears to contribute to chronic eyelid and meibomian gland inflammation and dysfunction. […] Inflammation causes corneal epithelial cells to produce fibroblast growth factors and pro-angiogenic factors such as vascular endothelial growth factor (VEGF). […] In response, conjunctival endothelial cells produce more MMPs, and the limbal epithelial cells, which are capable of producing neovascularization and opacification, migrate beyond their normal limbal location onto the cornea. […] This all contributes to triggering angiogenesis and corneal neovascularization.

• #47 Molecular Vision: Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models

  http://www.molvis.org/molvis/v27/323/

  The increase in cathelicidin levels in rosacea patients could be amplified via the expression of the protease-activated receptor 2 (PAR-2), which is activated by KLK-5 and known to mediate inflammation in various tissues, including the skin. […] The meibomian glands are sebaceous glands located in the epidermis of the lower and upper eyelids, which secrete meibum, a source of tear lipids. […] One of the main eye signs of ocular rosacea is MGD, as observed in several previous studies. […] The proinflammatory factors secondary to MGD cause inflammatory signs in eyelid edges. […] The mechanisms underlying the development of erythema in animals have not been approved as exactly mimicking those seen in humans with erythema associated with rosacea. […] Despite major advances in understanding the pathophysiology of cutaneous and ocular rosacea, the exact mechanisms are still poorly understood.

• #48 Molecular Vision: Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models

  http://www.molvis.org/molvis/v27/323/

  The increase in cathelicidin levels in rosacea patients could be amplified via the expression of the protease-activated receptor 2 (PAR-2), which is activated by KLK-5 and known to mediate inflammation in various tissues, including the skin. […] The meibomian glands are sebaceous glands located in the epidermis of the lower and upper eyelids, which secrete meibum, a source of tear lipids. […] One of the main eye signs of ocular rosacea is MGD, as observed in several previous studies. […] The proinflammatory factors secondary to MGD cause inflammatory signs in eyelid edges. […] The mechanisms underlying the development of erythema in animals have not been approved as exactly mimicking those seen in humans with erythema associated with rosacea. […] Despite major advances in understanding the pathophysiology of cutaneous and ocular rosacea, the exact mechanisms are still poorly understood.

• #49 Efficacy of azithromycin 1.5% eye drops in childhood ocular rosacea with phlyctenular blepharokeratoconjunctivitis | Journal of Ophthalmic Inflammation and Infection | Full Text

  https://joii-journal.springeropen.com/articles/10.1186/1869-5760-3-38

  The primary mechanism of childhood ocular rosacea is chronic meibomitis. Staphylococcal infection in the meibomian glands is probably secondary and may induce conjunctival and corneal inflammation by a T lymphocyte immune response against bacterial parietal antigens or toxins. The phlyctenules and corneal infiltrates are the result of a type IV cell-mediated late hypersensitivity reaction according to the Gell and Coombs’ classification. […] Azithromycin is a macrolide antibiotic characterized by a broad antibacterial spectrum, a long half-life related to its tissue and cell penetration, and anti-inflammatory properties. […] Azithromycin is a new treatment option for cutaneous rosacea and seems to be as effective as tetracyclines, and its efficacy in treating ocular rosacea has been demonstrated when administered orally.

• #50

  https://journals.lww.com/corneajrnl/fulltext/2025/04000/ocular_rosacea__an_updated_review.20.aspx

  The loss of homeostasis between the antiinflammatory and proinflammatory factors contributes to the vasodilation, vascular hyperreactivity, and disruption of the ocular surface integrity observed in ocular rosacea. […] The complex nature of ocular rosacea, with its interplay of immune, vascular, and neurosensory factors, underscores the need for a comprehensive approach to understanding and managing this condition as it presents a challenge in clinical practice. […] Recent studies have highlighted the potential significance of the ocular microbiome in the pathogenesis of ocular rosacea. […] The genetic basis of ocular rosacea remains uncertain, but emerging evidence suggests that genetic factors play a role in the development of and susceptibility to this condition. […] Ocular rosacea is characterized by vascular abnormalities, including vasodilation and telangiectasia, contributing to the characteristic erythema and flushing observed in this condition. […] The pathophysiologic mechanisms underlying the cutaneous and ocular manifestations of rosacea are likely shared as both conditions are characterized by altered innate immune responses, vascular dysfunction, and neurogenic inflammation.

• #51 Ocular Rosacea: An Updated Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11872267/

  Ocular rosacea is characterized by immune system dysfunction. Rosacea seems to cause an excessive activation of the innate immune system, specifically toll-like receptors (TLRs) and the complement system. […] The pathogenesis of ocular rosacea involves a complex interplay between the innate and adaptive immune systems, resulting in chronic ocular surface inflammation. […] The genetic basis of ocular rosacea remains uncertain, but emerging evidence suggests that genetic factors play a role in the development of and susceptibility to this condition. […] Ocular rosacea is characterized by vascular abnormalities, including vasodilation and telangiectasia, contributing to the characteristic erythema and flushing observed in this condition. […] The complex nature of ocular rosacea, with its interplay of immune, vascular, and neurosensory factors, underscores the need for a comprehensive approach to understanding and managing this condition as it presents a challenge in clinical practice.

• #52 Rosacea: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2015/0801/p187.html

  The etiology of rosacea is unknown but is likely multifactorial. Factors involved in the pathophysiology include the dense presence of sebaceous glands on the face, the physiology of the nerve innervation, and the vascular composition of the skin. Numerous triggers initiate or aggravate the clinical manifestations of rosacea, including ultraviolet light, heat, spicy foods, and alcohol. […] A predilection for fair-skinned individuals of Celtic or northern European descent suggests a genetic component to rosacea. However, no specific gene has been identified. Patients with the genetic predisposition have a receptor that mediates neovascular regulation. When exposed to triggers, neuropeptide release (flushing, edema) occurs, resulting in recruitment of proinflammatory cells to the skin. […] More than 50% of patients with cutaneous rosacea have ocular symptoms that may include tearing, foreign body sensation, itching, photophobia, and blurred vision.

• #53 Rosacea: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2015/0801/p187.html

  The etiology of rosacea is unknown but is likely multifactorial. Factors involved in the pathophysiology include the dense presence of sebaceous glands on the face, the physiology of the nerve innervation, and the vascular composition of the skin. Numerous triggers initiate or aggravate the clinical manifestations of rosacea, including ultraviolet light, heat, spicy foods, and alcohol. […] A predilection for fair-skinned individuals of Celtic or northern European descent suggests a genetic component to rosacea. However, no specific gene has been identified. Patients with the genetic predisposition have a receptor that mediates neovascular regulation. When exposed to triggers, neuropeptide release (flushing, edema) occurs, resulting in recruitment of proinflammatory cells to the skin. […] More than 50% of patients with cutaneous rosacea have ocular symptoms that may include tearing, foreign body sensation, itching, photophobia, and blurred vision.

• #54 Rosacea: Practical Guidance and Challenges for Management | CCID

  https://www.dovepress.com/rosacea-practical-guidance-and-challenges-for-clinical-management-peer-reviewed-fulltext-article-CCID

  Additionally, Toll-like receptor 2 (TLR2), a member of the TLR family and innate immunity detection system, is highly active in rosacea patients. It typically responds to stimuli including the environment, extreme temperatures, microbial skin colonization, chemical and physical trauma, and ultraviolet (UV) light exposure. TLR2 activity also promotes expression of KLK5, further exacerbating this pathway of increased expression of LL-37. Additional immune players that contribute to rosacea include matrix metalloproteases (MMPs), specifically MMP2 and MMP9, and mast cells, which also contribute to downstream KLK5 and LL-37 activity. […] […] New potential therapeutic target genes have been discovered with gene ontology analysis. Genomic association studies have identified three human leukocyte antigen (HLA) alleles and two single-nucleotide polymorphisms (SNPs) to be associated with rosacea, which have also been associated with autoimmune diseases such as type 1 diabetes and celiac disease. […]

• #55 Ocular Rosacea – EyeWiki

  https://eyewiki.org/Ocular_Rosacea

  Rosacea is thought to be an inflammatory condition with altered immune system responses and vascular dysregulation. […] Patients with ocular rosacea have abnormally enhanced sensitivity to common environmental stimuli, such as sun exposure, extremes of weather, spicy foods, heated beverages, emotional stress, strenuous exercise, alcohol and caffeine consumption (vasodilatory effects), certain cosmetics, medications (amiodarone, niacin, beta blockers, topical steroids, nasal steroids), high doses of vitamins B6 and B12, and dairy products. […] These factors contribute to activation of the inflammatory response and immune system, which expresses an enhanced level of Toll-like receptor 2 (TLR2) in the epidermis. […] Upregulated TLR2 in keratinocytes leads to an increase in activity of an enzyme serine protease, KLK5, which has a role in cathelicidin production.

• #56 Ocular Rosacea – EyeWiki

  https://eyewiki.org/Ocular_Rosacea

  Rosacea is thought to be an inflammatory condition with altered immune system responses and vascular dysregulation. […] Patients with ocular rosacea have abnormally enhanced sensitivity to common environmental stimuli, such as sun exposure, extremes of weather, spicy foods, heated beverages, emotional stress, strenuous exercise, alcohol and caffeine consumption (vasodilatory effects), certain cosmetics, medications (amiodarone, niacin, beta blockers, topical steroids, nasal steroids), high doses of vitamins B6 and B12, and dairy products. […] These factors contribute to activation of the inflammatory response and immune system, which expresses an enhanced level of Toll-like receptor 2 (TLR2) in the epidermis. […] Upregulated TLR2 in keratinocytes leads to an increase in activity of an enzyme serine protease, KLK5, which has a role in cathelicidin production.

• #57 Rosacea: Symptoms, Causes, and Management – DermNet

  https://dermnetnz.org/topics/rosacea

  The pathogenesis of rosacea is thought to be multifactorial and includes: […] Dysregulation of the immune response may lead to excessive inflammation, vasodilation, lymphatic dilatation, and angiogenesis. […] In the skin of patients with rosacea, there is increased expression and activity of toll-like receptor 2, cathelicidins, kallikrein 5, and mast cells. […] The result is an exaggerated innate immune reaction to the initial trigger. […] Increased Th17 expression can increase levels of cathelicidin LL-37 in keratinocytes and drive further inflammation. […] The most significant environmental trigger is UV radiation; affected skin is more sensitive to exposure. UV radiation can damage the dermis and increase skin inflammation. […] Ocular rosacea (lid margin telangiectasia, blepharitis, keratitis/conjunctivitis/sclerokeratitis/anterior uveitis). […] General management […] First-line medical management […] If severe: azithromycin, doxycycline.

• #58 Rosacea, the Eye, and the Gut – Modern Optometry

  https://modernod.com/articles/2022-nov-dec/rosacea-the-eye-and-the-gut

  Research has shown a connection between the gut and the skin in those with rosacea. For example, intestinal and dermatologic dysbiosis have appeared together in individuals with inflammatory skin disorders. Studies have also shown an increased prevalence of gastrointestinal disorders such as Helicobacter pylori infection, small intestinal bacterial overgrowth, Celiac disease, Crohn disease, and ulcerative colitis in patients with rosacea compared with controls.

• #59 Rosacea and the Microbiome: A Systematic Review | springermedizin.de

  https://www.springermedizin.de/rosacea-and-the-microbiome-a-systematic-review/18572828

  Cathelicidin may also represent a link between rosacea and irritable bowel disease (IBD), as significant elevations of this peptide were noted in the colonic mucosa of patients with IBD. […] Despite these immunologic features, it is unclear whether microorganisms are causative agents or innocent bystanders in rosacea. […] In other words, does dysbiosis precipitate rosacea, or does the altered cutaneous microenvironment precipitate dysbiosis? […] An association was noted between D. folliculorum and inflammatory markers, suggesting a deleterious activation of the innate immune system. […] This microorganism has been demonstrated to produce antigenic proteins that potentially play a role in PPR, ETR, and ocular rosacea. […] The pathogenic link is difficult to establish, as antibiotics are independently helpful in the treatment of each disease.

• #60 Rosacea and the Microbiome: A Systematic Review | springermedizin.de

  https://www.springermedizin.de/rosacea-and-the-microbiome-a-systematic-review/18572828

  Investigators theorize that circulating cytokines, particularly TNF, may play a role in this striking relationship. […] In addition to TNF, SIBO may alter immunity and trigger rosacea by the augmentation of other cytokines which suppress IL-17 and stimulate the Th1-mediated immune response. […] Future studies should further investigate the role of the GI microbiome in the pathogenesis of rosacea, as intraluminal agents such as rifaximin have already been shown to have beneficial effects.

• #61 Rosacea and the Microbiome: A Systematic Review | springermedizin.de

  https://www.springermedizin.de/rosacea-and-the-microbiome-a-systematic-review/18572828

  Investigators theorize that circulating cytokines, particularly TNF, may play a role in this striking relationship. […] In addition to TNF, SIBO may alter immunity and trigger rosacea by the augmentation of other cytokines which suppress IL-17 and stimulate the Th1-mediated immune response. […] Future studies should further investigate the role of the GI microbiome in the pathogenesis of rosacea, as intraluminal agents such as rifaximin have already been shown to have beneficial effects.

• #62 Rosacea and the Microbiome: A Systematic Review | springermedizin.de

  https://www.springermedizin.de/rosacea-and-the-microbiome-a-systematic-review/18572828

  Various mechanisms of this theorized association have been proposed, one of which describes H. pylori as a trigger of inflammation via cytotoxins and gastrin-induced flushing. […] A compromise in the mucosa, either through changes in the microbiome or autoimmune disease, may result in pernicious substances entering the bloodstream and affecting peripheral sites. […] Previous studies have linked inflammatory skin diseases with an imbalanced gut microbiome. […] Kendall points out that the PKKS is significantly activated in patients with intestinal inflammation and is likewise consistently elevated in patients with rosacea versus controls. […] The Danish cohort study by Egeberg et al. noted increased risk of new-onset IBS and subsequently diagnosed CeD in subjects with rosacea. […] According to a study by Parodi et al., patients with rosacea were 13 times more likely to have SIBO than control patients.

• #63 Rosacea and the Microbiome: A Systematic Review | springermedizin.de

  https://www.springermedizin.de/rosacea-and-the-microbiome-a-systematic-review/18572828

  Various mechanisms of this theorized association have been proposed, one of which describes H. pylori as a trigger of inflammation via cytotoxins and gastrin-induced flushing. […] A compromise in the mucosa, either through changes in the microbiome or autoimmune disease, may result in pernicious substances entering the bloodstream and affecting peripheral sites. […] Previous studies have linked inflammatory skin diseases with an imbalanced gut microbiome. […] Kendall points out that the PKKS is significantly activated in patients with intestinal inflammation and is likewise consistently elevated in patients with rosacea versus controls. […] The Danish cohort study by Egeberg et al. noted increased risk of new-onset IBS and subsequently diagnosed CeD in subjects with rosacea. […] According to a study by Parodi et al., patients with rosacea were 13 times more likely to have SIBO than control patients.

• #64 Rosacea and the Microbiome: A Systematic Review | springermedizin.de

  https://www.springermedizin.de/rosacea-and-the-microbiome-a-systematic-review/18572828

  Various mechanisms of this theorized association have been proposed, one of which describes H. pylori as a trigger of inflammation via cytotoxins and gastrin-induced flushing. […] A compromise in the mucosa, either through changes in the microbiome or autoimmune disease, may result in pernicious substances entering the bloodstream and affecting peripheral sites. […] Previous studies have linked inflammatory skin diseases with an imbalanced gut microbiome. […] Kendall points out that the PKKS is significantly activated in patients with intestinal inflammation and is likewise consistently elevated in patients with rosacea versus controls. […] The Danish cohort study by Egeberg et al. noted increased risk of new-onset IBS and subsequently diagnosed CeD in subjects with rosacea. […] According to a study by Parodi et al., patients with rosacea were 13 times more likely to have SIBO than control patients.

• #65 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/

  The precise etiology and pathophysiologic mechanisms of cutaneous and ocular rosacea remain unknown, although different theories have been proposed. Several studies confirm the inflammatory nature of the disease. An elevated concentration of interleukin-1a and b and a greater activity of gelatinase B (metalloproteinase -9) and colagenase-2 (MMP-8) have been found in tear fluids of patients with ocular rosacea. Doxycycline, used in the treatment of cutaneous and ocular rosacea, decreases both MMP-8 and MMP-9 activity. Tumor necrosis factor (TNF-alfa) was also elevated in rosacea. Significant overexpression of ICAM-1 (intercellular adhesion molecule 1) and HLA-DR, inflammatory markers, was observed in conjunctival epithelial cells of patients with rosacea. […] Recently, studies have shown that disease exacerbation is stimulated by normal external environmental factors, leading to unique activation of pro-inflammatory systems as well as innate immune responses. Molecular studies propose that the enhanced sensitivity of patients with rosacea may be caused by abnormal recognition of common environmental stimuli. Factors that trigger the innate immune system lead to an increase in the expression of certain cytokines and anti-microbial molecules in the skin. Cathelicidin, one of these antimicrobial peptides, has both vasoactive and pro-inflammatory actions and is implicated in the pathogenesis of this disorder.

• #66 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/?lang=en

  Additionally, local proteases (serine protease KLK5) that control the production of cathelicidin in epidermis were also abnormally expressed in rosacea patients. To further test their hypothesis, researchers injected abnormal cathelicidin or protease that produce these peptides in the skin of mice and observed similar inflammatory features of the disease found in humans. […] Observation of higher amounts of receptors of the recognition system, Toll-like receptor 2 (TLR2), in the epidermis of patients with rosacea explained the overreaction of these patients to environmental stimuli, since enhanced action of TLR2 in keratinocytes leads to an increase in serine protease KLK5 and cathelicidin production. […] Interestingly, tetracyclines, which improve signs and symptoms of rosacea, are known to inhibit expression and activity of several matrix metalloproteinases, as well as a class of proteases that activate cathelicidin, sustaining this theory.

• #67 Efficacy of azithromycin 1.5% eye drops in childhood ocular rosacea with phlyctenular blepharokeratoconjunctivitis | Journal of Ophthalmic Inflammation and Infection | Full Text

  https://joii-journal.springeropen.com/articles/10.1186/1869-5760-3-38

  The primary mechanism of childhood ocular rosacea is chronic meibomitis. Staphylococcal infection in the meibomian glands is probably secondary and may induce conjunctival and corneal inflammation by a T lymphocyte immune response against bacterial parietal antigens or toxins. The phlyctenules and corneal infiltrates are the result of a type IV cell-mediated late hypersensitivity reaction according to the Gell and Coombs’ classification. […] Azithromycin is a macrolide antibiotic characterized by a broad antibacterial spectrum, a long half-life related to its tissue and cell penetration, and anti-inflammatory properties. […] Azithromycin is a new treatment option for cutaneous rosacea and seems to be as effective as tetracyclines, and its efficacy in treating ocular rosacea has been demonstrated when administered orally.

• #68 Efficacy of azithromycin 1.5% eye drops in childhood ocular rosacea with phlyctenular blepharokeratoconjunctivitis | Journal of Ophthalmic Inflammation and Infection | Full Text

  https://joii-journal.springeropen.com/articles/10.1186/1869-5760-3-38

  Our study showed that topical azithromycin 1.5% is a very effective treatment of ocular rosacea in children. Its efficacy on conjunctival and corneal inflammation is remarkable. […] A biphasic effect was observed in this study. The effect on ocular redness was very fast, within a month, whereas phlyctenules and corneal infiltrates took several months to heal. This may point to different mechanisms. Ocular redness might be related to bacterial toxin production. Phlyctenules and corneal infiltrates are thought to be caused by a type IV cell-mediated delayed hypersensitivity reaction against parietal staphylococcal antigens. In addition to its antibiotic effect, azithromycin also has anti-inflammatory effects. Indeed, it has been shown to reduce the production of the pro-inflammatory cytokines IL-12 and IL-6 by macrophages in vitro; to suppress matrix metalloproteases 2 and 9, nuclear transcription factor NFkB, and Toll-like receptor 2 in corneal epithelial cells in vitro; and to inhibit macrophage and dendritic cell migration after corneal burn in a mouse model.

• #69 Efficacy of azithromycin 1.5% eye drops in childhood ocular rosacea with phlyctenular blepharokeratoconjunctivitis | Journal of Ophthalmic Inflammation and Infection | Full Text

  https://joii-journal.springeropen.com/articles/10.1186/1869-5760-3-38

  Our study showed that topical azithromycin 1.5% is a very effective treatment of ocular rosacea in children. Its efficacy on conjunctival and corneal inflammation is remarkable. […] A biphasic effect was observed in this study. The effect on ocular redness was very fast, within a month, whereas phlyctenules and corneal infiltrates took several months to heal. This may point to different mechanisms. Ocular redness might be related to bacterial toxin production. Phlyctenules and corneal infiltrates are thought to be caused by a type IV cell-mediated delayed hypersensitivity reaction against parietal staphylococcal antigens. In addition to its antibiotic effect, azithromycin also has anti-inflammatory effects. Indeed, it has been shown to reduce the production of the pro-inflammatory cytokines IL-12 and IL-6 by macrophages in vitro; to suppress matrix metalloproteases 2 and 9, nuclear transcription factor NFkB, and Toll-like receptor 2 in corneal epithelial cells in vitro; and to inhibit macrophage and dendritic cell migration after corneal burn in a mouse model.

• #70 A Basic Guide to Ocular Rosacea – Modern Optometry

  https://modernod.com/articles/2021-july-aug/a-basic-guide-to-ocular-rosacea

  Ocular rosacea is a subtype of facial rosacea […] Ocular rosacea is a large contributor to and cause of dry eye disease. […] The cause of rosacea is unclear, but it is linked to various factors such as a malfunctioning immune response, the vascular system including the neurovascular system, genetic predispositions, and hypersensitivity to Demodex. […] Ocular rosacea is a large contributor to and cause of dry eye disease (DED). […] The main difference in confirming ocular rosacea as a contributing factor to a patients DED is the noticeable increase in redness, inflammation, and telangiectasia along the lid margin, as well as the possible accompanying facial rosacea component. […] Intense pulsed light (IPL) therapy is a noninvasive, nonpharmacologic option in which high intensity light with specific filters is used to target the inflammation, redness, and abnormal vasculature associated with facial and ocular rosacea. […] By treating the abnormal vasculature, IPL therapy is able to address the root cause of the inflammation. […] IPL therapy has also been shown to kill Demodex, a contributor to rosacea symptoms.

• #71 A Basic Guide to Ocular Rosacea – Modern Optometry

  https://modernod.com/articles/2021-july-aug/a-basic-guide-to-ocular-rosacea

  Ocular rosacea is a subtype of facial rosacea […] Ocular rosacea is a large contributor to and cause of dry eye disease. […] The cause of rosacea is unclear, but it is linked to various factors such as a malfunctioning immune response, the vascular system including the neurovascular system, genetic predispositions, and hypersensitivity to Demodex. […] Ocular rosacea is a large contributor to and cause of dry eye disease (DED). […] The main difference in confirming ocular rosacea as a contributing factor to a patients DED is the noticeable increase in redness, inflammation, and telangiectasia along the lid margin, as well as the possible accompanying facial rosacea component. […] Intense pulsed light (IPL) therapy is a noninvasive, nonpharmacologic option in which high intensity light with specific filters is used to target the inflammation, redness, and abnormal vasculature associated with facial and ocular rosacea. […] By treating the abnormal vasculature, IPL therapy is able to address the root cause of the inflammation. […] IPL therapy has also been shown to kill Demodex, a contributor to rosacea symptoms.

• #72 A Basic Guide to Ocular Rosacea – Modern Optometry

  https://modernod.com/articles/2021-july-aug/a-basic-guide-to-ocular-rosacea

  Ocular rosacea is a subtype of facial rosacea […] Ocular rosacea is a large contributor to and cause of dry eye disease. […] The cause of rosacea is unclear, but it is linked to various factors such as a malfunctioning immune response, the vascular system including the neurovascular system, genetic predispositions, and hypersensitivity to Demodex. […] Ocular rosacea is a large contributor to and cause of dry eye disease (DED). […] The main difference in confirming ocular rosacea as a contributing factor to a patients DED is the noticeable increase in redness, inflammation, and telangiectasia along the lid margin, as well as the possible accompanying facial rosacea component. […] Intense pulsed light (IPL) therapy is a noninvasive, nonpharmacologic option in which high intensity light with specific filters is used to target the inflammation, redness, and abnormal vasculature associated with facial and ocular rosacea. […] By treating the abnormal vasculature, IPL therapy is able to address the root cause of the inflammation. […] IPL therapy has also been shown to kill Demodex, a contributor to rosacea symptoms.

• #73 Clinical Findings, Follow-up and Treatment Results in Patients with Ocular Rosacea – Turkish Journal of Ophthalmology

  https://oftalmoloji.org/articles/clinical-findings-follow-up-and-treatment-results-in-patients-with-ocular-rosacea/doi/tjo.48902

  Considering the anti-inflammatory effect of cyclosporine A and its efficacy in the treatment of meibomitis, we also prescribed 0.05% topical cyclosporine four times daily as an adjunct therapy. Significant improvement in ocular signs and symptoms was observed with this treatment in particular. […] Corneal neovascularization, especially in the inferior quadrant, occurs with ocular rosacea. […] The underlying cause of corneal thinning has not been clearly determined, but an elevated level of matrix metalloproteinases (especially type 9) in the inferior tear meniscus is believed to be responsible for stromal thinning and perforation.

• #74 Advances in the Pathogenesis and Treatment of Rosacea: A Phenotype-Based Therapeutic Approach

  https://www.mdpi.com/2079-9284/11/1/11

  Rosacea is a common chronic inflammatory skin disorder that mainly affects the central face. Its pathogenesis is complex and still not completely understood. It encompasses innate and adaptive immune system dysregulation, neurovascular dysfunction, and genetic and environmental factors. […] Although the real nature of rosacea remains largely elusive, it is known that its pathogenesis encompasses a complex interplay between innate and adaptive immune system dysregulation, neurovascular dysfunction, and genetic and environmental factors. […] The dysregulation of toll-like receptor (TLR)2-kallikrein (KLK5)-cathelicidin(LL37) pathways has a crucial role in the pathogenesis of rosacea. […] The complex immunomodulatory role of LL-37 is driven by multiple pathways. […] Interestingly, LL-37 activates the Janus kinase (JAK)/signal transducer and transcription activator (STAT) signaling pathway, which mediates monocyte chemotaxis and IL-6-, IL-8-, and TNFα expression.

• #75 Rosacea: Symptoms, Causes, and Management – DermNet

  https://dermnetnz.org/topics/rosacea

  The pathogenesis of rosacea is thought to be multifactorial and includes: […] Dysregulation of the immune response may lead to excessive inflammation, vasodilation, lymphatic dilatation, and angiogenesis. […] In the skin of patients with rosacea, there is increased expression and activity of toll-like receptor 2, cathelicidins, kallikrein 5, and mast cells. […] The result is an exaggerated innate immune reaction to the initial trigger. […] Increased Th17 expression can increase levels of cathelicidin LL-37 in keratinocytes and drive further inflammation. […] The most significant environmental trigger is UV radiation; affected skin is more sensitive to exposure. UV radiation can damage the dermis and increase skin inflammation. […] Ocular rosacea (lid margin telangiectasia, blepharitis, keratitis/conjunctivitis/sclerokeratitis/anterior uveitis). […] General management […] First-line medical management […] If severe: azithromycin, doxycycline.

• #76 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/

  The precise etiology and pathophysiologic mechanisms of cutaneous and ocular rosacea remain unknown, although different theories have been proposed. Several studies confirm the inflammatory nature of the disease. An elevated concentration of interleukin-1a and b and a greater activity of gelatinase B (metalloproteinase -9) and colagenase-2 (MMP-8) have been found in tear fluids of patients with ocular rosacea. Doxycycline, used in the treatment of cutaneous and ocular rosacea, decreases both MMP-8 and MMP-9 activity. Tumor necrosis factor (TNF-alfa) was also elevated in rosacea. Significant overexpression of ICAM-1 (intercellular adhesion molecule 1) and HLA-DR, inflammatory markers, was observed in conjunctival epithelial cells of patients with rosacea. […] Recently, studies have shown that disease exacerbation is stimulated by normal external environmental factors, leading to unique activation of pro-inflammatory systems as well as innate immune responses. Molecular studies propose that the enhanced sensitivity of patients with rosacea may be caused by abnormal recognition of common environmental stimuli. Factors that trigger the innate immune system lead to an increase in the expression of certain cytokines and anti-microbial molecules in the skin. Cathelicidin, one of these antimicrobial peptides, has both vasoactive and pro-inflammatory actions and is implicated in the pathogenesis of this disorder.

• #77 SciELO Brazil – Ocular rosacea: a review Ocular rosacea: a review

  https://www.scielo.br/j/abo/a/shtJWX5bvNDPLXSw4SF9tzC/?lang=en

  The precise etiology and pathophysiologic mechanisms of cutaneous and ocular rosacea remain unknown, although different theories have been proposed. Several studies confirm the inflammatory nature of the disease. An elevated concentration of interleukin-1a and b and a greater activity of gelatinase B (metalloproteinase -9) and colagenase-2 (MMP-8) have been found in tear fluids of patients with ocular rosacea. Doxycycline, used in the treatment of cutaneous and ocular rosacea, decreases both MMP-8 and MMP-9 activity. Tumor necrosis factor (TNF-alfa) was also elevated in rosacea. Significant overexpression of ICAM-1 (intercellular adhesion molecule 1) and HLA-DR, inflammatory markers, was observed in conjunctival epithelial cells of patients with rosacea. […] Recently, studies have shown that disease exacerbation is stimulated by normal external environmental factors, leading to unique activation of pro-inflammatory systems as well as innate immune responses. Molecular studies propose that the enhanced sensitivity of patients with rosacea may be caused by abnormal recognition of common environmental stimuli. Factors that trigger the innate immune system lead to an increase in the expression of certain cytokines and anti-microbial molecules in the skin.

• #78

  https://journals.lww.com/corneajrnl/fulltext/2025/04000/ocular_rosacea__an_updated_review.20.aspx

  The loss of homeostasis between the antiinflammatory and proinflammatory factors contributes to the vasodilation, vascular hyperreactivity, and disruption of the ocular surface integrity observed in ocular rosacea. […] The complex nature of ocular rosacea, with its interplay of immune, vascular, and neurosensory factors, underscores the need for a comprehensive approach to understanding and managing this condition as it presents a challenge in clinical practice. […] Recent studies have highlighted the potential significance of the ocular microbiome in the pathogenesis of ocular rosacea. […] The genetic basis of ocular rosacea remains uncertain, but emerging evidence suggests that genetic factors play a role in the development of and susceptibility to this condition. […] Ocular rosacea is characterized by vascular abnormalities, including vasodilation and telangiectasia, contributing to the characteristic erythema and flushing observed in this condition. […] The pathophysiologic mechanisms underlying the cutaneous and ocular manifestations of rosacea are likely shared as both conditions are characterized by altered innate immune responses, vascular dysfunction, and neurogenic inflammation.

• #79 Ocular Rosacea: An Updated Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC11872267/

  Ocular rosacea is characterized by immune system dysfunction. Rosacea seems to cause an excessive activation of the innate immune system, specifically toll-like receptors (TLRs) and the complement system. […] The pathogenesis of ocular rosacea involves a complex interplay between the innate and adaptive immune systems, resulting in chronic ocular surface inflammation. […] The genetic basis of ocular rosacea remains uncertain, but emerging evidence suggests that genetic factors play a role in the development of and susceptibility to this condition. […] Ocular rosacea is characterized by vascular abnormalities, including vasodilation and telangiectasia, contributing to the characteristic erythema and flushing observed in this condition. […] The complex nature of ocular rosacea, with its interplay of immune, vascular, and neurosensory factors, underscores the need for a comprehensive approach to understanding and managing this condition as it presents a challenge in clinical practice.

• #80 Ocular Rosacea—a Review – touchOPHTHALMOLOGY

  https://touchophthalmology.com/ocular-immunology/journal-articles/ocular-rosacea-a-review/

  Demodex folliculorum mites have been found in higher densities in skin scrapings or superficial standardized skin biopsies of patients with rosacea, and a decrease in mite density after treatment has been reported. […] It is likely that an underlying genetic predisposition becomes manifest on exposure to environmental factors. Gene dysregulation may also be responsible for the derangement in inflammatory mediators and/or instability of the neurovascular component.

• #81 Ocular Rosacea | IntechOpen

  https://www.intechopen.com/chapters/53160

  Demodex folliculorum is a saprophytic mite that is found in normal flora of the skin. There are studies demonstrating that the Demodex density increased in rosacea patients. […] Bacillus olenorium serum immunoreactivity was detected in ocular rosacea patients. Its proteins cause high immune reactions. […] Staphylococcus epidermidis and Propionibacterium acnes that are found commonly in lid flora are accused microorganisms for their production of high levels of bacterial lipases. […] OR was found to be associated with the increased tear fluid levels of several inflammatory mediators such as interleukin-1 (IL-1) and gelatinase B activity. […] The meibomian glands of rosacea patients cause keratinization of epithelial cells, end up with thickening of secretions, plugging of the orifices, and trapping of the secretions.

• #82 Molecular Vision: Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models

  http://www.molvis.org/molvis/v27/323/

  The increase in cathelicidin levels in rosacea patients could be amplified via the expression of the protease-activated receptor 2 (PAR-2), which is activated by KLK-5 and known to mediate inflammation in various tissues, including the skin. […] The meibomian glands are sebaceous glands located in the epidermis of the lower and upper eyelids, which secrete meibum, a source of tear lipids. […] One of the main eye signs of ocular rosacea is MGD, as observed in several previous studies. […] The proinflammatory factors secondary to MGD cause inflammatory signs in eyelid edges. […] The mechanisms underlying the development of erythema in animals have not been approved as exactly mimicking those seen in humans with erythema associated with rosacea. […] Despite major advances in understanding the pathophysiology of cutaneous and ocular rosacea, the exact mechanisms are still poorly understood.

• #83 Seeing Red: How Ocular Rosacea Impacts the Cornea

  https://www.reviewofoptometry.com/article/seeing-red-how-ocular-rosacea-impacts-the-cornea

  Chronic inflammation causes atrophy of the meibomian glands themselves, decreasing meibum production. […] Ocular rosacea patients also characteristically have an increased eyelid margin density of Demodex. […] An immune response to Demodex infestation on eyelash follicles and within meibomian glands also appears to contribute to chronic eyelid and meibomian gland inflammation and dysfunction. […] Inflammation causes corneal epithelial cells to produce fibroblast growth factors and pro-angiogenic factors such as vascular endothelial growth factor (VEGF). […] In response, conjunctival endothelial cells produce more MMPs, and the limbal epithelial cells, which are capable of producing neovascularization and opacification, migrate beyond their normal limbal location onto the cornea. […] This all contributes to triggering angiogenesis and corneal neovascularization.

• #84

  https://journals.lww.com/corneajrnl/fulltext/2025/04000/ocular_rosacea__an_updated_review.20.aspx

  The loss of homeostasis between the antiinflammatory and proinflammatory factors contributes to the vasodilation, vascular hyperreactivity, and disruption of the ocular surface integrity observed in ocular rosacea. […] The complex nature of ocular rosacea, with its interplay of immune, vascular, and neurosensory factors, underscores the need for a comprehensive approach to understanding and managing this condition as it presents a challenge in clinical practice. […] Recent studies have highlighted the potential significance of the ocular microbiome in the pathogenesis of ocular rosacea. […] The genetic basis of ocular rosacea remains uncertain, but emerging evidence suggests that genetic factors play a role in the development of and susceptibility to this condition. […] Ocular rosacea is characterized by vascular abnormalities, including vasodilation and telangiectasia, contributing to the characteristic erythema and flushing observed in this condition. […] The pathophysiologic mechanisms underlying the cutaneous and ocular manifestations of rosacea are likely shared as both conditions are characterized by altered innate immune responses, vascular dysfunction, and neurogenic inflammation.

• #85 Rosacea: Diagnosis and Treatment | AAFP

  https://www.aafp.org/pubs/afp/issues/2015/0801/p187.html

  The etiology of rosacea is unknown but is likely multifactorial. Factors involved in the pathophysiology include the dense presence of sebaceous glands on the face, the physiology of the nerve innervation, and the vascular composition of the skin. Numerous triggers initiate or aggravate the clinical manifestations of rosacea, including ultraviolet light, heat, spicy foods, and alcohol. […] A predilection for fair-skinned individuals of Celtic or northern European descent suggests a genetic component to rosacea. However, no specific gene has been identified. Patients with the genetic predisposition have a receptor that mediates neovascular regulation. When exposed to triggers, neuropeptide release (flushing, edema) occurs, resulting in recruitment of proinflammatory cells to the skin. […] More than 50% of patients with cutaneous rosacea have ocular symptoms that may include tearing, foreign body sensation, itching, photophobia, and blurred vision.

• #86 Rosacea, the Eye, and the Gut – Modern Optometry

  https://modernod.com/articles/2022-nov-dec/rosacea-the-eye-and-the-gut

  Research has shown a connection between the gut and the skin in those with rosacea. For example, intestinal and dermatologic dysbiosis have appeared together in individuals with inflammatory skin disorders. Studies have also shown an increased prevalence of gastrointestinal disorders such as Helicobacter pylori infection, small intestinal bacterial overgrowth, Celiac disease, Crohn disease, and ulcerative colitis in patients with rosacea compared with controls.

• #87 Rosacea and the Microbiome: A Systematic Review | springermedizin.de

  https://www.springermedizin.de/rosacea-and-the-microbiome-a-systematic-review/18572828

  Various mechanisms of this theorized association have been proposed, one of which describes H. pylori as a trigger of inflammation via cytotoxins and gastrin-induced flushing. […] A compromise in the mucosa, either through changes in the microbiome or autoimmune disease, may result in pernicious substances entering the bloodstream and affecting peripheral sites. […] Previous studies have linked inflammatory skin diseases with an imbalanced gut microbiome. […] Kendall points out that the PKKS is significantly activated in patients with intestinal inflammation and is likewise consistently elevated in patients with rosacea versus controls. […] The Danish cohort study by Egeberg et al. noted increased risk of new-onset IBS and subsequently diagnosed CeD in subjects with rosacea. […] According to a study by Parodi et al., patients with rosacea were 13 times more likely to have SIBO than control patients.

• #88 Molecular Vision: Cutaneous and ocular rosacea: Common and specific physiopathogenic mechanisms and study models

  http://www.molvis.org/molvis/v27/323/

  The increase in cathelicidin levels in rosacea patients could be amplified via the expression of the protease-activated receptor 2 (PAR-2), which is activated by KLK-5 and known to mediate inflammation in various tissues, including the skin. […] The meibomian glands are sebaceous glands located in the epidermis of the lower and upper eyelids, which secrete meibum, a source of tear lipids. […] One of the main eye signs of ocular rosacea is MGD, as observed in several previous studies. […] The proinflammatory factors secondary to MGD cause inflammatory signs in eyelid edges. […] The mechanisms underlying the development of erythema in animals have not been approved as exactly mimicking those seen in humans with erythema associated with rosacea. […] Despite major advances in understanding the pathophysiology of cutaneous and ocular rosacea, the exact mechanisms are still poorly understood.

• #89

  https://www.jcdr.net/article_fulltext.asp?issn=0973-709x&year=2022&month=November&volume=16&issue=11&page=WC09-WC11&id=17127

  Ocular rosacea is a diagnostic enigma to clinicians as it is underdiagnosed because of overlapping sign and symptoms. […] The aetiology of ocular rosacea is relatively unknown. Current hypothesis focus on the dysfunction of the immune, vascular, and neurovascular systems, which seem to be at the heart of pathogenesis, triggered by microbial or physical stimuli. […] Despite major advances in understanding the pathophysiology of cutaneous and ocular rosacea, the exact mechanisms are still poorly understood.

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