Up To Date Medical Info Related To Conjunctivitis **Includes A Special Section on Diagnostic Advances and Recently FDA approved point of care medical devices**

15 January 2006

Conjunctivitis: Differentiating Allergic, Bacterial & Viral Conjunctivitis

Conjunctivitis Blog Outline

  • Introduction

  • Definition

  • Common Causes of Conjunctivitis

  • Symptoms & Signs

  • Risk Factors

  • Spread of Disease

  • Signs & History Suggestive of More Serious Disease

  • Characteristics Of Infectious Conjunctivitis

  • Diagnosis

  • Management

  • Treatment

  • Summary


Introduction


Approximately 2% of all primary care visits and 1% of all emergency room visits are related to conjunctivitis. Adenovirus represents the most common form of a red eye worldwide and most frequently presents to the primary care physician.  According to the 2002 article in the American Journal of Infection Control by Guinan et al, more than 164 million school days are missed annually in American public schools due to the spread of infectious diseases and approximately 3 million school days are lost as a result of acute conjunctivitis. A study by the Carnegie Foundation revealed that missed school days represent the main problem that 83% of teachers face in their school.

Clinically, it can sometimes be difficult to distinguish bacterial and allergic from viral conjunctivitis


Definition


Conjunctivitis is an inflammation of the conjunctiva, a thin, transparent layer covering the surface of the inner eyelid and the front of the eye. It affects people of all ages.

Acute conjunctivitis from various etiologies is characterized by common symptoms and signs including a red eye, discharge, eyelash matting or crusting, foreign body sensation, and tearing.


Common Causes of Conjunctivitis

Conjunctivitis is usually caused by infection or allergy. It is frequently referred to as "pink eye" and is the most common acute eye disorder seen by primary care pediatricians and family physicians. Typically, it is caused by a virus more often than bacteria.

The differential diagnosis for acute conjunctivitis includes:
  1. Viral conjunctivitis (Adenoviral most commonly)

  2. Bacterial conjunctivitis (other than Chlamydia or Gonococcal)

  3. Allergic conjunctivitis

  4. Herpes Simplex conjunctivitis

  5. Chlamydia conjunctivitis

  6. Gonococcal conjunctivitis

  7. Vernal / Atopic conjunctivitis

The differential diagnosis for acute conjunctivitis in the newborn (Ophthalmia neonatorum < 1 month old) includes:
  1. Chemical conjunctivitis

  2. Herpes Simplex conjunctivitis

  3. Chlamydia conjunctivitis

  4. Gonococcal conjunctivitis

  5. Bacterial conjunctivitis (other than Chlamydia or Gonococcal)

General History, Symptoms & Signs

A red eye associated with (any of the following):  

  • Both bacterial and viral conjunctivitis often have a history of contact with others with "pink eye" within the preceding 2-3 weeks

  • Viral conjunctivitis is often associated with a tender pre-auricular lymph node or a recent upper respiratory infection

  • Irritation; itchiness; tearing; foreign body sensation

  • Clear or yellow discharge that may make the eyelids stick together, especially in the morning

  • Swelling of eyelids


Risk Factors

Conjunctivitis affects people at any age but tends to occur most often between the ages of 1 - 25 years of age. Preschoolers and school-age children get it most often because of crowding and lack of good hand-washing and hygiene.  Also, it is associated with swimming pools, daycare, day camps, college dorms, and military housing.


Spread of Disease

People can develop conjunctivitis by coming into direct contact with the tears or secretions from the eyes of an infected person and then touching their own eyes. Some viral particles may remain viable on surfaces for up to 49 days. Also conjunctivitis, when associated with an upper respiratory infection (common cold), can be spread by droplets (e.g., coughing, sneezing). Adenovirus can be recovered from the eye and throat for as long as three weeks after the onset of clinical symptoms


Signs & History Suggestive of a More Serious Disease

  1. Severe eye pain

  2. Change in vision

  3. Extreme sensitivity to light

  4. Contact lens use

  5. History of recent trauma to the eye

  6. History of underlying rheumatological disease
** These above criteria require consultation by a specialist.

Characteristics of Infectious Conjunctivitis


Infectious conjunctivitis may be bacterial or viral in nature. It is most often caused by a virus and viral conjunctivitis occurs more often than bacterial conjunctivitis.

In viral conjunctivitis there is redness, clear tearing or crusting, usually occurs in older children and adults, and is often associated with pharyngitis or rhinitis.

In bacterial conjunctivitis, the eye is red and often associated with a more muco-purulent discharge, the affected child is often a younger pre-schooler and there may be an associated otitis media.


  • Allergic

     

  • Background & Epidemiology

Allergic conjunctivitis occurs very frequently. It is estimated to affect 20 percent of the population on an annual basis and approximately one-half of these people have a personal or family history of atopy. Allergic conjunctivitis may be divided into 5 major subcategories including 1) Seasonal allergic conjunctivitis, 2) Perennial allergic conjunctivitis, 3) Vernal keratoconjunctivitis, 4) Atopic keratoconjunctivitis , and 5) Giant papillary conjunctivitis.

Seasonal (SAC) and perennial allergic conjunctivitis (PAC) combine to account for about two thirds of all allergic eye disease cases. The prevalence of SAC and PAC tends to be the same as hay fever or allergic rhinitis. Atopic keratoconjunctivitis is a bilateral, severe, allergic inflammation of the conjunctiva found in a subset of patients with atopic dermatitis. Atopic dermatitis occurs in 3% of the population and 15-40% of these will develop atopic keratoconjunctivitis. Vernal Keratoconjunctivitis is a bilateral, severe, vision threatening allergic inflammation of the conjunctiva. It tends to seasonally affect prepubescent boys with allergic predisposition in hot, dry, climates such as the Mediterranean basin, West Africa, and Indian subcontinent. These children have a strong allergic predisposition with 70% having other manifestations of allergic or atopic disease. It is also associated with a strong family history of allergic or atopic disease. Giant papillary conjunctivitis accounts for 0.5-1.0% of eye disease in most countries. It is an allergic inflammation of the upper palpebral conjunctiva associated with prosthetic wear, sutures, or from contact lens use. It is estimated to occur in 1-5% of rigid gas-permeable contact lens wearers and 10-15% of hydrogel (soft) contact lens wearers. All forms of allergic conjunctivitis are characterized predominantly as a type I hypersensitivity reaction and demonstrate increased serum and tear levels of IgE.

  • Physical Findings
Allergic conjunctivitis is associated with a boggy edematous palpebral and bulbar conjunctiva.  A papillary reaction is often seen along with a thick, ropy mucoid discharge.  At times, the limbus can be associated with thickening consistent with limbal follicles.

  • Bacterial Conjunctivitis



  • Background & Epidemiology

Bacterial conjunctivitis is a common condition in all areas of the United States.  Several studies demonstrate that bacterial conjunctivitis represents 25-50% of all causes of conjunctivitis. Bacterial conjunctivitis tends to have a more mucoid to purulent discharge.  The more common causes common bacterial conjunctivitis include:


  • Gram-positive for the following cocci - Staphylococcus epidermidis, Streptococcus pyogenes, and Streptococcus pneumoniae

  • Gram-negative for the following cocci - Neisseria meningitidis and Moraxella lacunata

  • Gram-negative for the following rods - genus Haemophilus and family Enterobacteriaceae

  • Hyperpurulent conjunctivitis usually is caused by N gonorrhoeae.
N gonorrhoeae, C trachomatis, and other bacteria (mainly staphylococcal species and S pneumoniae) cause conjunctivitis of the newborn.

  • Chlamydia

Chlamydiae are obligate intracellular organisms from bacteria that now comprise 3 species. They include the following: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. C trachomatis is associated with serotypes A, B, Ba, C, while cases of inclusion conjunctivitis and ophthalmia neonatorum tend to be related to serotypes D-K.

Chlamydia is the causative organism in 2% of patients with acute conjunctivitis and is the most common cause of chronic follicular conjunctivitis. In India, one study demonstrated a prevalence of 35% of all cases of conjunctivitis.

This organism may cause the following three clinical syndromes: trachoma, adult inclusion conjunctivitis, and neonatal conjunctivitis. In the US, it is estimated that 1 in 300 patients who have genital chlamydial disease develop adult inclusion conjunctivitis while at least 70% of women with chlamydial conjunctivitis are estimated to have a genital chlamydial infection. The majority of patients have no genital symptoms.

This condition is typically observed in the young sexually active patients aged 15-35 years. Each year more than 155,000 infants are born to Chlamydia infected mothers, and the organism is transmitted to the fetus in more than 50% of such deliveries. Approximately 20% and 50% of all infants born to infected mothers develop chlamydial conjunctivitis.


  • N. Gonorrhea
Gonorrhea is most frequently spread during sexual contact or transmitted from the mother's genital tract to the newborn during birth to cause ophthalmia neonatorum.  N gonorrhoeae is a gram-negative, intracellular, aerobic diplococcus.  In most industrialized countries the prevalence of gonorrhoea in pregnant women is less than 1%; in developing countries the rates are between 3% and 15%, more than 50% being due to penicillinase-producing Neisseria gonorrhoeae strains (PPNG). The rate of transmission from mother to newborn is between 30% and 50%. In adults, it is a rare, severe, purulent conjunctivitis that is acquired from a gonorrheal contact or from self-inoculation during a gonorrheal genital infection. Gonococcal  conjunctivitis is the most serious, usually occurring 24-48 hours following birth.   It typically affects only one eye.

  • Physical Findings

  • Papillary pattern of conjunctival inflammation

  • No preauricular adenopathy with the exception of Chlamydia and gonorrhea

  • Discharge is copious; discharge quality is thick and purulent

  • Conjunctival injection is usually marked

  • Patients develop a hyperacute conjunctivitis, associated with marked lid edema, chemosis, and purulent discharge.

  • A conjunctival membrane may be present.

  • Corneal ulcer may occur and rapidly progress to perforation, if treatment is delayed.

  • Viral Conjunctivitis



  • Background & Epidemiology

Adenovirus is by far the most common cause but other viral causes include herpes simplex virus (HSV), varicella-zoster virus (VZV), picornavirus (enterovirus 70, coxsackie A24), poxvirus (molluscum contagiosum, vaccinia), and human immunodeficiency virus (HIV).  The prevalence of adenoviral conjunctivitis is found to represent 20% - 91% of all conjunctivitis world wide. In a preliminary study of 50 consecutive patients presenting to the Wills Eye Hospital Emergency Room in Philadelphia, PA from July 2003 to October 2003 revealed a prevalence of adenoviral conjunctivitis of 62 % ((31 out of 50) - unpublished data). This attack rate was similar to the results of a 2002 study out of the Philippines that also demonstrated a viral etiology in 60% of cases. A multi-center FDA clinical trial out of US and Europe showed an adenoviral attack rate of 28%.

Viral conjunctivitis in East Asia including Japan, Korea, and Taiwan is caused mainly by adenovirus and affects approximately one million people in Japan per year. In one Japanese study, adenovirus was isolated from 91.2% of cases of clinically diagnosed epidemic keratoconjunctivitis in which the etiological agent was determined virologically. A second Japanese study of 1105 patients with viral conjunctivitis, 49% were found to be caused by adenovirus. Finally, a large study of three Asian cities confirmed adenovirus accounted for 70% of all cases of epidemic keratoconjunctivitis.  

HSV may occur without the classic skin vesicles and corneal epithelial dendrites.  Studies have demonstrated that a nondescript form of HSV causes about 3-5% of all infectious conjunctivitis.  Outside the US, enterovirus 70, coxsackie A24 are relatively frequent causes of acute hemorrhagic conjunctivitis and forms of EKC.

Because adenoviral conjunctivitis demonstrates seasonal variability it is often higher during the summer months. This may be explained by the increased risk of transfer seen with summer related activities such as swimming and day camps. It also seems that urban environments and decreased hygiene may facilitate spreading of the disease.

  • Physical Findings

  • An ipsilateral preauricular lymphadenopathy

  • Superficial puntate keratitis

  • Swelling and erythema of the lid

  • Conjunctival hyperemia

  • Chemosis

  • Follicular reaction

  • Papillary hypertrophy

  • Subconjunctival and petechial hemorrhage

Diagnosis



  • Gram Stain          
Gram stain is should be performed when considering a diagnosis of bacterial conjunctivitis especially if N gonorrhoeae is under consideration.  N gonorrhoeae is associated with intracellular gram negative diplococci.   Eosinophils seen on Gram stain are indicative of allergic conjunctivitis but can be seen in parasitic causes.

  • RPS Adeno Detector
The FDA has approved a new, rapid point of care diagnostic test for viral conjunctivitis called the RPS Adeno Detector. The test completed a multi-center, blinded FDA clinical trial to compare the efficacy of the RPS Adeno Detector against cell culture for detecting adenoviral conjunctivitis. This study demonstrates the high degree of sensitivity and specificity of the RPS Adeno Detector at correctly identifying patients with adenoviral conjunctivitis in just 10 minutes.

  • Cell Culture

Cell culture remains the gold standard.  However, cultures of the conjunctiva are rarely performed because of the considerable time delay in viral and or bacterial isolation results, expense of performing the tests, and self limited nature of typical conjunctivitis.  It does not provide point of care information. Obtain cultures in all newborns, neonates, persons who are immunosuppressed, or when N gonorrhoeae is under consideration as the etiology.

  • Polymerase Chain Reaction (PCR)

PCR is an excellent means of establishing a reliable diagnosis of acute infectious conjunctivitis. The technique has been shown to be more sensitive, accurate, and rapid than culture for detecting many causes of conjunctivitis. However,  PCR is not routinely performed because it is not FDA approved and still requires sending out a sample that may take 1-2 days to process, technical equipment and expertise in running and interpreting samples, and tends to cost up to 6 times as much as viral culture.  It does not provide point of care information.


Management


Viral and other non-purulent types of conjunctivitis do not require antimicrobial treatment. These are self-limited conditions that may last 1-3 weeks. Often these children are treated mistakenly for prolonged periods of time with both topical and systemic antibiotics. In some situations, 13-26% of the time, the topical antibiotic itself may cause an allergic reaction or corneal toxicity resulting in a persistent red eye.

Acute bacterial conjunctivitis is a self limited condition. However, the use of topical antibiotic treatment is recommended because it hastens healing considerably and it eradicates the bacterial pathogen allowing children to return to daycare centers and schools within 48 hours of treatment. There is usually no need to use topical treatment for more than 2 to 5 days when complete resolution should have occurred. Treatment should be applied to both eyes, even if only one eye appears to be infected. Topical application should be applied four times a day.


Treatment


  • Allergic
Treatment consists of removal of any specific environmental triggers and a combination of supportive care including cool compresses and artificial tears for mild cases. The use of topical medications is reserved for more moderate cases and includes a combination of vasoconstrictors/antihistamines, mast cell stabilizers, nonsteroidal anti-inflammatory agents, and cyclosporine. Topical steroids may be used in severe cases. A trial of oral antihistamines is frequently utilized for moderate disease.

  • Bacterial
Routine bacterial conjunctivitis in a nonimmunocompromised state, requires treatment with a topical antibiotic

  • Chlamydial infection of the newborn requires systemic treatment of the neonate, the mother, and at-risk contacts.

  • The neonate may be treated with oral erythromycin suspension for 2-3 weeks

  • The mother and at-risk contacts may be treated with doxycycline 100 mg orally twice daily for 7 days

  • N gonorrhoeae infection of the newborn also requires systemic treatment of the neonate, the mother, and at-risk contacts.

  • The neonate may be treated with intravenous aqueous penicillin G 100 units per kg per day in 4 divided doses for 1 week

  • The mother and at-risk contacts may be treated with a single dose of intramuscular ceftriaxone 125 mg followed by oral doxycycline 100 mg twice daily for 7 days.

  • Prophylaxis against ophthalmia neonatorum is a major force in the worldwide effort to prevent blindness. Common regimens are the instillation of 1% silver nitrate solution, or 1% tetracycline ointment, or 0.5% erythromycin ointment.
               
  • Viral

Treatment is generally supportive and consists predominantly of frequent application of preservative free artificial tears. Over the counter topical anti-histamines and cool compresses can sometimes provide relief from severe itching. Rarely, severe infections associated with pseudo-membranes and sub-epithelial infiltrates may necessitate a short course of topical steroids. It is imperative to stress the contagious nature of this virus and recommend vigorous hand washing to prevent further spread of the disease.

Since HSV can manifest as a typical appearing viral conjunctivitis with no associated skin vesicles or cornea dendrites, topical steroids should be used with caution as these can promote worsening HSV related epithelial disease.  Also, topical steroids have been shown in rabbit animal models to prolong the ocular shedding of adenovirus by several weeks.

Adenovirus is a very robust virus that can survive outside the body on hard surfaces and has been cultured from such surfaces up to 7 weeks after an infection. It is somewhat resistant to alcohol disinfection, and it is recommended that a dilute bleach based cleaner be used for proper disinfection.

  • Supportive measures  include:

  1. Apply cool compresses to the infected eye(s) three to four times per day for 10-15 minutes using a clean washcloth each time. This should help reduce itching and swelling and provide some comfort.

  2. Wash your hands frequently and keep them away from your eyes in order to reduce or prevent recontamination.

  3. Avoid rubbing your eyes to decrease irritation of the area.

  4. Wear sunglasses if your eyes are sensitive to the light.

  5. Avoid exposure to the irritants that may be causing the conjunctivitis.

  6. Dispose of old eye makeup if the culture for bacteria is positive.

  7. Use a clean pillowcase each night. (Pillowcase can be changed every other day and turned over nightly).

  8. Avoid wearing contact lenses while you are using medications or if your eyes are uncomfortable. Cleanse contact lenses thoroughly.

Prognosis

Viral conjunctivitis, although usually benign and self-limited, tends to follow a longer course than acute bacterial conjunctivitis, lasting for approximately 2-4 weeks while bacterial usually only lasts for about 7-10 days.  Allergic conjunctivitis tends to be recurring and seasonal.

Complications

  • Allergic conjunctivitis, especially atopic or vernal forms of allergic conjunctivitis, can cause a sterile shield ulcer causing significant visual loss

  • Bacterial conjunctivitis usually resolves without any complications.  However, special forms of bacterial conjunctivitis such as Chlamydial or Gonococcal are associated with more severe complications.


  • Chlamydial infection in the newborn can lead to pneumonia and/or otitis media.

  • N gonorrhoeae

  • Infections with N meningitidis may require systemic antibiotics to prevent meningitis Sepsis and meningitis caused by Neisseria gonorrhoeae can be life threatening.

  • Penetration of the cornea can occur within 2 days in patients with untreated N gonorrhoeae.


  • Viral Conjunctivitis


  • EKC, A form of adenoviral conjunctivitis is typically self-limiting and resolves spontaneously within 2-3 weeks but can be associated with significant morbidity including subepithelial infiltrates (SEI or superficial corneal inflammatory deposits), lacrimal drainage scarring, and symblepharon.

  • About 30% develop a pseudomembrane lining the inferior palpebral conjunctiva

  • In 20-50% of cases, SEI’s can persist from a few weeks to months. These sterile infiltrates cause decreased visual acuity, foreign body sensation, glare, and light sensitivity

  • Subepithelial corneal infiltrates can cause decreased visual acuity, foreign body sensation, glare, and light sensitivity

  • Lacrimal drainage problems (tear drainage problems) leading to chronic epiphora or excessive tearing

  • Conjunctival scarring and symblepharon

Follow up Care

  1. Usually patients are seen 10-14 days later for uncomplicated cases

  2. Any patient requiring topical corticosteroids should be observed routinely to monitor for side effects, including infection, elevated intraocular pressure, and cataract formation.

Summary  & Advances


Currently infectious conjunctivitis is a clinical diagnosis and cell cultures and PCR are not routinely done. The RPS Adeno Detector would make a laboratory confirmation of the diagnosis of viral conjunctivitis readily available. Because the RPS Adeno Detector test empowers a physician to accurately make a diagnosis and appropriately treat or not treat a patient, it ultimately allows a physician to practice better medicine. Physicians often feel pressured by their patients to institute a treatment even if they think it is unnecessary. When patients visualize a positive test result themselves, physicians can achieve better patient acceptance for more supportive therapies.

This could dramatically limit over use of unnecessary antibiotics and thus, reduce ocular antibiotic resistance, toxicity, and allergies. It could also help isolate a contagious person who will not improve with topical antibiotics and may require more time away from work, school, or daycare.