Conjunctivitis

Epidemiology and Etiology

Epidemiology

• Most common non-traumatic eye complaint
• Estimated incidence in the United States is 6 million people per year 
• Most frequently found in infants, school-age children, and the elderly

Etiology

Infectious conjunctivitis

• Viral 
  • Adenoviruses (most common cause, 65%–90% of cases)
  • Herpes simplex virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview (most common cause in children and infants)
  • Varicella-zoster virus Varicella-Zoster Virus Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Varicella-zoster infections are highly contagious and transmitted through aerosolized respiratory droplets or contact with infected skin lesions. Varicella-Zoster Virus/Chickenpox (most common in the elderly)
  • Picornavirus (enterovirus and coxsackievirus Coxsackievirus Coxsackievirus is a member of a family of viruses called Picornaviridae and the genus Enterovirus. Coxsackieviruses are single-stranded, positive-sense RNA viruses, and are divided into coxsackie group A and B viruses. Both groups of viruses cause upper respiratory infections, rashes, aseptic meningitis, or encephalitis. Coxsackievirus cause acute hemorrhagic conjunctivitis)
  • Molluscum contagiosum Molluscum contagiosum Molluscum contagiosum is a viral infection limited to the epidermis and is common in children below 5 years of age. Lesions appear as grouped, flesh-colored, dome-shaped papules with central umbilication. Molluscum Contagiosum (causes chronic follicular conjunctivitis)
  • HIV (usually affects posterior segment of the eye)
• Bacterial 
  • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus (most common cause in adults)
  • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pneumoniae
  • Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus influenzae (most common cause in children)
  • Moraxella Moraxella Moraxella is a genus of gram-negative diplococci, with M. catarrhalis being the most clinically relevant species. M. catarrhalis is part of the normal flora of the upper respiratory tract, but it can cause infection in susceptible individuals. The infection is transmitted through respiratory droplets and can lead to chronic obstructive pulmonary disease (COPD) exacerbations in adults and otitis media in children. Moraxella catarrhalis
  • Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria gonorrhoeae (more common in newborns) or Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria meningitidis 
  • Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia trachomatis
  • Gram-negative enteric flora

Noninfectious conjunctivitis

• Allergic (e.g., from airborne allergens)
• Nonallergic (e.g., “dry eye syndrome,” associated with blepharitis Blepharitis Blepharitis is an ocular condition characterized by eyelid inflammation. Anterior blepharitis involves the eyelid skin and eyelashes, while the posterior type affects the meibomian glands. Often, these conditions overlap. Blepharitis, Sjögren’s syndrome, reactive arthritis Reactive arthritis Reactive arthritis is a seronegative autoimmune spondyloarthropathy that occurs in response to a previous gastrointestinal (GI) or genitourinary (GU) infection. The disease manifests as asymmetric oligoarthritis (particularly of large joints in the lower extremities), enthesopathy, dactylitis, and/or sacroiliitis. Reactive Arthritis)

Diagnosis

The diagnosis is mainly clinical.

• Viral conjunctivitis: 
  • History of recent viral infection (not mandatory)
    • If symptoms are recurrent/chronic →  conjunctival smear, cultures, or viral isolation required 
    • Mononuclear cells and lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes are seen on Giemsa stain of conjunctival scrapings.
• Bacterial conjunctivitis:
  • If persistent or severe disease, diagnosis is uncertain, and in newborn conjunctivitis →  conjunctival scrapings, culture, or PCR required
  • Findings for various bacterial infections: 
    • Bacterial conjunctivitis shows a predominance of neutrophils on Giemsa staining
    • In gonococcal ophthalmia neonatorum, Gram stain of exudate shows gram-negative intracellular diplococci; culture in modified Thayer-Martin medium grows N. gonorrhoea.
    • In chlamydial conjunctivitis, Giemsa stain shows neutrophils with inclusion bodies and plasma cells.
• Allergic conjunctivitis: 
  • Clinical history, signs and symptoms are usually sufficient.
  • Eye pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain is not characteristic of allergic conjunctivitis, and more serious disorders must be ruled out, including angle-closure glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma, scleritis, or episcleritis.
  • If patient does not respond to therapy, referral to an opthalmologist is indicated, who may refer to an allergist for possible skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin testing to detect the causative allergen(s).
• In cases of visual impairment, significantly increased photophobia, inability to keep the eye open, abnormal pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil's size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Physiology and Abnormalities of the Pupil reaction to light, or severe headache with nausea, other diagnoses must be ruled out (and specialist referrals are indicated):
  • Glaucoma
  • Uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea
  • Keratitis
  • Meningitis (especially in infants)

Management

Viral conjunctivitis

• Uncomplicated viral conjunctivitis is treated symptomatically. 
• Antihistamine drops/artificial tears
• Herpes simplex infection is treated with a topical antiviral (e.g., ganciclovir).

Bacterial conjunctivitis

• Topical broad-spectrum antibiotics (e.g., erythromycin, trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim-polymyxin B) 
• Neisserial and chlamydial infections Chlamydial infections Chlamydial infections are a group of infectious diseases caused by bacteria belonging to the Chlamydiaceae family. The 3 species that can infect humans are Chlamydia trachomatis, C. pneumoniae, and C. psittaci. The most common infection is an STI caused by C. trachomatis, which affects the genitourinary tract. Chlamydial Infections require systemic treatment
  • For gonococcal conjunctivitis, a single dose of intramuscular ceftriaxone plus oral azithromycin is given. Alternative agents are cefotaxime or ceftazidime.
  • For chlamydial neonatal conjunctivitis, oral erythromycin is preferred.
• Prevention of ophthalmia neonatorum: prenatal maternal screening, systemic antibiotic treatment, and prophylaxis for newborns

Allergic conjunctivitis

• Antihistamine drops/artificial tears
• Oral antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines and mast-cell stabilizers (e.g., ketotifen)
• Cold compresses
• Nonsteroidal anti-inflammatory drugs (e.g., ketorolac)
• Corticosteroids (e.g., fluorometholone)

Differential Diagnosis

The following conditions enter into the differential diagnoses of conjunctivitis:

• Glaucoma: a condition caused by acutely or chronically increased intraocular pressure or — since up to 40% of those affected do not have increased IOP — there may be heightened ganglion susceptibility to normal pressure, problems with the microcirculation or extracellular matrix in the optic nerve
  Treatment includes surgery plus topical beta-blockers and prostaglandins. If left untreated, both the common open-angle and the less common angle-closure glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma can lead to blindness.
• Uveitis Uveitis Uveitis is the inflammation of the uvea, the pigmented middle layer of the eye, which comprises the iris, ciliary body, and choroid. The condition is categorized based on the site of disease; anterior uveitis is the most common. Diseases of the Uvea: an ophthalmic emergency caused by the inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the uvea, which includes the iris and ciliary body, the choroid. The cause can be either infectious (mostly viral) or noninfectious. Common symptoms include burning of the eye, redness, blurry vision, photophobia, floaters, and irregular pupils. Treatment includes topical or systemic steroids, antivirals, and topical atropine.
• Keratitis: a mostly infectious acute or chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the cornea. Other causes include allergy and trauma. Patients commonly present with a red, teary painful eye, impaired vision, and photophobia. Treatment depends on the underlying condition and includes topical antivirals, antibiotics, and antifungals.
• Meningitis (especially in infants): a potentially life-threatening inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the leptomeninges, mostly due to viruses or bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview. Common symptoms include headaches, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, a stiff neck, altered mental status, photophobia, and phonophobia. Young children often present with nonspecific symptoms. Treatment consists of antibiotics, antivirals, and corticosteroids. 
• Subconjunctival hemorrhage: This condition is usually asymptomatic. The clinical appearance, with demarcated areas of extravasated blood just beneath the surface of the eye, is generally both obvious and diagnostic. It may occur spontaneously or with Valsalva-associated mechanisms (e.g., coughing, sneezing, or vomiting). The diagnosis is confirmed by normal acuity and the absence of discharge, photophobia, or foreign body sensation. It typically resolves within 1 to 2 weeks.
• Chalazion Chalazion A chalazion is one of the most common inflammatory lesions of the eyelid. It is caused by obstruction of the Meibomian or Zeis glands, leading to granulomatous inflammation and resulting in a firm, rubbery, slow-growing nodule that is typically non-tender. Chalazion: presents as painless localized eyelid swelling and firm rubbery nodule. It is caused by the obstruction of Zeis or Meibomian glands.
• Dry eye syndrome: a multifactorial disease of the ocular surface with loss of tear film and ocular symptoms, also known as keratoconjunctivitis sicca. Patients present with dryness and redness of the eye, general irritation, gritty/burning sensation, foreign body sensation, paradoxical excessive tearing, photophobia, or blurred vision. 
• Blepharitis: an inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the eyelid margin with eye irritation. Patients usually present with red, swollen or itchy eyelids; a gritty burning sensation; conjunctival injection; crusting and matting of the eyelashes in the morning; photophobia; and blurred vision.