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The Ultimate Guide to Conjunctivitis Differential Diagnosis

Nov 10, 2021
101 min read
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“Pink eye” is one of the most common complaints eyecare providers encounter. This is not surprising considering “pink eye” is a catch-all term used to describe red, watery eyes. Likewise, conjunctivitis, the clinical term for “pink eye” is also a broad classification that encompasses many different conditions with varied underlying causes but similar signs and symptoms. Conjunctivitis affects nearly six million people annually in the U.S.1 and accounts for about 1% of all primary care visits and 28% of ER visits.2,3

Clinical presentation

Conjunctivitis specifically refers to the inflammation of the bulbar and palpebral conjunctiva of the eye. This inflammation results in varying degrees of injection and edema, which gives “pink eye” its classic reddish-pink, swollen appearance and is often accompanied by some form of discharge.4 The underlying causes of conjunctivitis vary and include infectious etiologies such as bacterial, viral, fungal, and parasitic infections as well as noninfectious causes like allergies, inflammatory conditions, and mechanical irritation.

Accurately diagnosing the specific cause of conjunctivitis has been shown to be a challenge for providers, as 80% of cases of infectious conjunctivitis are treated with antibiotics, while only 30% of cases are truly bacterial in nature.5 However, while the different forms of conjunctivitis may present in similar fashions, there are key differences, although sometimes subtle, that help differentiate them.

It is critical for eyecare providers (ECPs) to identify these differences quickly and accurately, as the treatments for the various forms of conjunctivitis can differ significantly. Fortunately, there are several hallmark features that make delineating the different causes of conjunctivitis relatively straightforward.

Conjunctivitis can be caused by many underlying factors, but all forms tend to share the basic presentation of red, irritated eyes, with some form of discharge as seen in Figure 1.


Figure 1

Making a diagnosis

Although all forms of conjunctivitis may appear similar at a superficial level, a careful history and thorough examination will often be all that is needed to determine the exact underlying cause.

Two key pieces of information will allow ECPs to quickly categorize the nature of the condition.

1) Is the patient experiencing any discharge?

  • If so, is it watery, mucoid, or stringy or ropey?
  • What color is the discharge?

2) Is there a reaction of the palpebral conjunctiva?

  • Are papillae present?
  • Are follicles present?
  • Is there a mixed reaction?

These two pieces of information–the quality of discharge and type of palpebral reaction present–will allow providers to broadly categorize the conjunctivitis as bacterial, viral, or allergic in nature, and by adding a few additional pieces of information an even more specific diagnosis can be made.

Download the Conjunctivitis Differential Diagnosis Flowcharts Now!

If the patient is experiencing watery discharge with a follicular reaction, that points to a viral cause. If the discharge is more mucopurulent and is yellow-green or brownish in color along with a papillary reaction, then it is likely bacterial in nature. And if the discharge is ropey and clear with papillae, then it is likely allergic in origin, which is confirmed by the presence of itching (usually absent in other forms of conjunctivitis). However, if the patient is displaying mucoid discharge with a follicular or mixed reaction, this suggests a more systemic bacterial infection, such as chlamydia.

While the patient’s history and a few targeted questions can often broadly categorize the nature of the conjunctivitis between infectious and noninfectious, and even viral, bacterial, or allergic, clinical exam findings and pertinent patient history will provide the information required to make a specific diagnosis.

Some of the more important elements to examine include:

1) How long has the condition been going on?

  • Is it acute or chronic?

2) Is there corneal involvement? If so, what does it look like?

  • Are the lesions dendritic? Infiltrative? Ulcerative?

3) Are the lids or lashes involved?

  • Are there any lesions on the eyelids?
  • Is there any debris or discharge present on the lashes?

4) Are the lymph nodes swollen?

5) Are there any systemic symptoms?

  • Does the patient have a fever?
  • Does the patient have a rash?

6) Is the patient a contact lens wearer?

  • Do they sleep in their lenses?
  • Do they swim in their lenses or rinse them with tap water?

These additional pieces of information in conjunction with the previous broad categorization will greatly narrow the possible causes of a case and often lead to a specific diagnosis, such as a herpetic infection or contact lens-induced conjunctivitis.

There are diagnostic tests on the market that aid in differentiating the causes of conjunctivitis, including the QuickVue Adenoviral Conjunctivitis Test (Quidel), which can determine if the condition is viral in nature. While tests like these can be helpful, they may be impractical to perform in the midst of a busy clinic. Therefore, by understanding the key similarities and differences between the different forms of conjunctivitis ECPs can quickly and accurately diagnose the cause of a patient’s condition and initiate the appropriate treatment.

Included below are the broad categories of conjunctivitis such as bacterial, viral, fungal, and parasitic conjunctivitis, in addition to noninfectious forms such as allergic, inflammatory, and mechanical. These are further broken down into specific forms of conjunctivitis with a description of the hallmark signs and case history that differentiates each type.

Bacterial conjunctivitis


Bacterial conjunctivitis (BC) is the second leading cause of conjunctivitis in adults, and accounts for an estimated 30% of cases.6,5 BC primarily occurs in the winter and spring months.7 It tends to be more common in children than adults, as it accounts for 50-70% of cases of pediatric conjunctivitis.7 The hallmark sign of BC is mucoid or mucopurulent discharge, which is often colored (creamy-white or yellow-green to brown).8 In addition to eye redness, patients will typically report mild to moderate irritation or pain and light sensitivity, but discharge is routinely the main complaint as these patients will often report waking up with their eyes “crusted shut”.

Patients will also display a papillary reaction, and occasionally lid edema or chemosis. It is recommended that all cases involving copious, purulent discharge be cultured.9 There are numerous potential bacterial species that can cause conjunctivitis, but two of the most common are Haemophilus influenzae (a gram-negative bacterium), especially in children, and Staphylococcal species (gram-positive bacteria), which are more common in adults.10,11 The most common bacteria responsible for acute bacterial conjunctivitis include Haemophilus influenzae, Streptococcus pneumoniae, Pseudomonas aeruginosa, Neisseria gonorrhoeae, and Neisseria meningitides.11-13

Staphylococcus aureus and Moraxella lacunata are most frequently responsible for chronic bacterial conjunctivitis.14 Other potential bacterial species that are less commonly encountered include Streptococcus, Moraxella catarrhalis, Chlamydia trachomatis, Corynebacterium diphtheriae, and Mycobacterium tuberculosis.12,15,16

There are several potential avenues by which a bacterial infection can develop, such as touching an object or surface contaminated with bacteria and then touching or rubbing the eyes. Likewise, sharing contaminated towels, bedding, or makeup can also result in inoculation.7 Contact lens wearers are at greater risk of developing BC due to potential contamination of the lens, lens case or fingers when inserting or removing the lens.17 Another route of infection to be aware of, especially in younger adults, is oculo-genital contact that may occur during sexual activity.9

In other cases, bacterial infections arise from an overgrowth of normal microflora or transmission of bacteria between the sinuses and nasal mucosa to the conjunctiva.18 Acute cases of BC can develop within hours to days, while chronic forms take 2-7 days to develop and last at least 4 weeks.7,14

While most cases of BC are self-limiting and resolve in 1-2 weeks,6 some hyperacute forms involving particularly virulent bacteria pose significant risk and require urgent treatment.6 The use of topical antibiotics is helpful in quickening resolution and alleviating symptoms. A wide array of antibiotics can be utilized depending on the suspected organism responsible for the infection, though broad-spectrum antibiotics, such as fourth generation fluoroquinolones, are recommended to cover against a wide range of pathogens. Patients are also encouraged to launder all bedding and towels, discard any makeup, and dispose of contact lenses, lens cases, and solutions if the patient is a contact lens wearer.

As Figure 2 demonstrates, bacterial conjunctivitis is characterized by redness, papillae, and mucopurulent discharge.

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Figure 2

Acute bacterial conjunctivitis

Acute bacterial conjunctivitis can be caused by a number of bacterial species. The most common causes in children are H. influenzae, S. pneumoniae, and Moraxella catarrhalis.11 In adults, Staphylococcal species and Streptococcus pneumoniae are more common, with H. influenzae a potential culprit as well.11 Acute BC is relatively uncommon in adults and is much more likely in children.7

The typical signs and symptoms of acute BC include papillae on the palpebral conjunctiva, a scant to moderate amount of colored discharge, and mild to moderate irritation or pain and photophobia. Patients will often report waking up with their lids “crusted shut” and residual discharge may be noted on the lashes and lid margin as well.

These cases of conjunctivitis are usually self-limiting and resolve within 7-10 days;7 however, treatment with topical antibiotics can speed resolution and help alleviate symptoms.6 There are numerous antibiotics that can be successfully used to treat the condition and many broad-spectrum antibiotics are equally efficacious, so the antibiotic chosen often comes down to the suspected underlying pathogen, medication cost, availability, dosing, and any allergy concerns.

Polytrim (polymyxin B/trimethoprim) dosed QID for 7 days is an excellent option, especially for children, as are fluoroquinolones such as ciprofloxacin 0.3%, ofloxacin 0.3%, and moxifloxacin 0.5%, which have broad coverage and are also dosed QID for 7 days. These antibiotics have good coverage against both gram-positive and gram-negative bacteria, such as Staph and H. influenzae respectively, as well as relatively low dosing frequency which makes them appropriate first-line treatments.

If a significant amount of inflammation is present, a soft steroid, such as loteprednol etabonate 0.5%, dosed BID-QID for 7 days can also be used. Bacitracin or ciprofloxacin 0.3% ointment can also be used QHS as adjunct therapy to increase contact time with the ocular surface. Patients should also wash all bedding and towels and discard any makeup. It is important to note if the patient is a contact lens wearer, they should discontinue contact lens use and dispose of their lenses, lens case, and solution as each may be a potential source of contamination.

These patients should also be treated with a broad-spectrum antibiotic with good gram-negative coverage, ideally a fourth-generation fluoroquinolone, like moxifloxacin 0.5%, as they are at a higher risk of pseudomonas infection, which poses a risk to the cornea including ulceration and perforation if left untreated.19

Many consider steroid use contraindicated in the presence of infection, due to the risk of prolongment and potential worsening of the condition. However, it has been shown that when topical steroids are used for a short duration (2 weeks or less) in the treatment of bacterial conjunctivitis, these concerns are primarily theoretical and topical steroids can be used safely and effectively.20 However, if there is any sign of corneal ulceration or if the patient is a contact lens wearer, topical steroid use should be avoided.

Additionally, most cases of bacterial conjunctivitis are relatively mild, so the use of a steroid will rarely be needed. But if significant chemosis or inflammation is present, and the patient is highly symptomatic, topical steroids can be an effective adjunct therapy.

As seen in Figure 3, he discharge present in bacterial conjunctivitis is often colored rather than clear and can appear creamy-white, yellow-green, or brown