Conjunctivitis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [5]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [6]

Overview

Conjunctivitis is defined as inflammation of bulbar and/or palpebral conjunctiva. Conjunctivitis has many etiologies, but the majority of cases can be caused by allergies or infection. Viral conjunctivitis, typically caused by adenovirus, is a common, self-limiting condition. Bacterial conjunctivitis has many etiologies, such as Staphylococcus, Streptococcus, Corynebacterium, Haemophilus, Pseudomonas, and Moraxella. Allergic conjunctivitis may occur seasonally when pollen counts are high, and this type of conjunctivitis is a common occurrence in people who have other signs of allergic disease. Keratoconjunctivitis sicca (dry eye syndrome) is a multifactorial disease and associated with different medical conditions.

Pathophysiology

Pathogenesis

Infective Conjunctivitis

Infective conjunctivitis is an infection of the conjunctiva either caused by viruses or bacteria . Both the palpebral and the bulbar ocular conjunctival surfaces are usually affected, and typically become red and inflamed. Infective conjunctivitis is spread by:

• Direct contact with the infected person’s eye drainage or drainage from the person’s cough, sneeze, or runny nose
• Contact with the infected person’s fingers, hands or objects (eye makeup applicators, towels, shared eye medications)
• Adjacent infectious sites (rubbing of the eyes)

Any change in the host defense, or in the species of normal flora of the eye, such as Staphylococcus, Streptococcus, and Corynebacterium, can lead to clinical infection and conjunctivitis. Change in the normal flora can occurred by:

• External contamination
• Contact lens wear
• Swimming

Viral conjunctivitis, typically caused by adenovirus, is a common, self-limiting condition. Viral conjunctivitis is highly contagious, and patients should avoid direct or indirect contact with other healthy individuals. Acute hemorrhagic conjunctivitis may be caused by picornaviruses that are clinically similar to adenovirus conjunctivitis, but are more severe and hemorrhagic. Acute hemorrhagic conjunctivitis also occurs in epidemics, and is characterized by sudden onset of painful, swollen red eyes, conjunctival hemorrhage, and excessive tearing.

Neonatal Conjunctivitis

Neonatal conjunctivitis is occurring in a newborn during the first month of life, and often known as ophthalmia neonatorum. Neonatal conjunctivitis is mainly caused by sexually transmitted diseases agents such as Chlamydia trachomatis, Neisseria gonorrhoeae, and Herpes simplex virus (HSV). Chlamydia trachomatis is the most common cause of ophthalmia neonatorum in the developed countries because of higher prevalence of chlamydia as a sexually transmitted disease. The recognized routes of transmission of the organisms to the newborns include:

• Infected birth canal during vaginal birth
• Transmembrane transmission of the infection
• Transplacental transmission of the infectio

On gross pathology, It is characterized by eyelids edema, erythema of the palpebral conjunctiva, and purulent eye discharge. On a gram stained of conjunctival smear, one or more polymorph nuclear per oil immersion field may be detected. Additionally, neonatal conjunctivitis may caused by irritation. it is generally secondary to the instillation of silver nitrate drops for ocular prophylaxis.

Allergic Conjunctivitis

Airborne antigens may be involved in the pathogenesis of allergic conjunctivitis. Common airborne antigens include pollen, grass, and weeds.

Allergic conjunctivitis is often associated with atopic diseases, such as allergic rhinitis (most common), eczema, and asthma. Development of allergic conjunctivitis is the result of type 1 hypersensitivity (immediate hypersensitivity) reactions involving the conjunctiva. Type I hypersensitivity is an allergic reaction provoked by reexposure to a specific type of antigen or allergens. IgE and mast cells play an important role in these allergic inflammations. IgE mediated release of histamine and other mediators from mast cells and basophils

Combination of type 1 and type 4 hypersensitivity reactions may be responsible for giant papillary conjunctivitis. Also, prolonged mechanical irritation to the superior tarsal conjunctiva of the upper lid from foreign bodies may also be a contributing factor in giant papillary conjunctivitis.

Keratoconjunctivitis Sicca

Keratoconjunctivitis sicca (dry eye syndrome) is a multifactorial disease and associated with different medical conditions such as:

• Sjögren's syndrome
• Ocular surface disease
• Ocular allergy
• Dysfunction of the lacrimal gland with reduced tear production and mucin deficiency
• Anxiety disorder
• Depression

Keratoconjunctivitis sicca associated Sjögren's syndrome may caused by focal infiltration of the lacrimal gland and conjunctiva with CD4+ T cells and B cells. Focal infiltration can induce apoptosis, and this results in dysfunction of the lacrimal gland with reduced tear production. Additionally, keratoconjunctivitis sicca associated Sjögren's syndrome can lead to chronic inflammatory state with production of autoantibodies such as:

• Antinuclear antibody (ANA)
• Rheumatoid factor (RF)
• Fodrin (a cytoskeletal protein)
• Muscarinic M3 receptor
• Sjögren's syndrome-specific antibodies (anti-RO and anti-LA)

Superior Limbic Keratoconjunctivitis

Superior limbic keratoconjunctivitis (SLK) is disease characterized by inflammation of the upper palpebral and superior bulbar conjunctiva. On microscopic histopathological analysis, it is charactrized by keratinization of the superior limbus, corneal filaments, and conjunctival filaments. The exact pathogenesis of superior limbic keratoconjunctivitis is not fully understood, a mechanical hypothesis seems most attractive. It is thought that mechanical trauma from tight upper lids or loose redundant conjunctiva could lead to the disruption of normal epithelium. Also association between thyroid abnormalities (Graves ophthalmopathy) and superior limbic keratoconjunctivitis has been reported.

Gross Pathology

On gross pathology, the following are characteristic findings of conjunctivitis:

• Conjunctival injection
• Mucopurulent discharge or non-purulent discharge
• Pseudomembrane formation
• Chemosis
• Eyelid swelling
• Conjunctival hemorrhage (specific for Acute hemorrhagic conjunctivitis)

Microscopic histopathological analysis

On microscopic histopathological analysis, the following are characteristic findings of conjunctivitis:

• Mild spongiotic reaction pattern (low power view of the histology)
• Stromal infiltration by polymorphonuclear, leukocytes, plasma cells, mastocytes, and lymphocyte
• Eosinophils (allergic conjunctivitis)
• Numerous neutrophils (bacterial conjunctivitis)
• Hyperplastic with increase numbers of plasma cell (chronic conjunctivitis)
• epithelial cells Keratinization of the superior limbus (Superior limbic keratoconjunctivitis (SLK))
• Dyskeratosis (Superior limbic keratoconjunctivitis (SLK))

Images

The following are gross and microscopic images associated with conjunctivitis.

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  Viral conjunctivitis

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  Acute hemorrhagic conjunctivitis

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  Neonatal conjunctivitis<ref> Centers for Disease Control and Prevention's Public Health Image

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  Chlamydial conjunctivitis (Day 5-14)