Clinical Review & Education

Review

Conjunctivitis
A Systematic Review of Diagnosis and Treatment
Amir A. Azari, MD; Neal P. Barney, MD

CME Quiz at
IMPORTANCE Conjunctivitis is a common problem. jamanetworkcme.com and
CME Questions 1732

OBJECTIVE To examine the diagnosis, management, and treatment of conjunctivitis,

including various antibiotics and alternatives to antibiotic use in infectious conjunctivitis
and use of antihistamines and mast cell stabilizers in allergic conjunctivitis.

EVIDENCE REVIEW A search of the literature published through March 2013, using PubMed,
the ISI Web of Knowledge database, and the Cochrane Library was performed. Eligible
articles were selected after review of titles, abstracts, and references.

FINDINGS Viral conjunctivitis is the most common overall cause of infectious conjunctivitis
and usually does not require treatment; the signs and symptoms at presentation are
variable. Bacterial conjunctivitis is the second most common cause of infectious
conjunctivitis, with most uncomplicated cases resolving in 1 to 2 weeks. Mattering and
adherence of the eyelids on waking, lack of itching, and absence of a history of conjunctivitis
are the strongest factors associated with bacterial conjunctivitis. Topical antibiotics decrease
the duration of bacterial conjunctivitis and allow earlier return to school or work.
Conjunctivitis secondary to sexually transmitted diseases such as chlamydia and gonorrhea
requires systemic treatment in addition to topical antibiotic therapy. Allergic conjunctivitis is
encountered in up to 40% of the population, but only a small proportion of these individuals
seek medical help; itching is the most consistent sign in allergic conjunctivitis, and treatment
consists of topical antihistamines and mast cell inhibitors.
Author Affiliation: Department of
Ophthalmology and Visual Sciences,
CONCLUSIONS AND RELEVANCE The majority of cases in bacterial conjunctivitis are University of Wisconsin, Madison.
self-limiting and no treatment is necessary in uncomplicated cases. However, Corresponding Author: Amir A.
conjunctivitis caused by gonorrhea or chlamydia and conjunctivitis in contact lens wearers Azari, MD, Department of
should be treated with antibiotics. Treatment for viral conjunctivitis is supportive. Ophthalmology, Room F4/349,
University of Wisconsin Madison,
Treatment with antihistamines and mast cell stabilizers alleviates the symptoms of allergic
600 Highland Ave, Madison, WI
conjunctivitis. 53792 (amirazarimd@gmail.com).
Section Editor: Mary McGrae
JAMA. 2013;310(16):1721-1729. doi:10.1001/jama.2013.280318 McDermott, MD, Senior Editor.

C
onjunctiva is a thin, translucent membrane lining the an- A majority of conjunctivitis patients are initially treated by
terior part of the sclera and inside of the eyelids. It has 2 pri- mary care physicians rather than eye care professionals.
parts, bulbar and palpebral. The bulbar portion begins at Approxi- mately 1% of all primary care office visits in the United
the edge of the cornea and covers the visible part of the sclera; States are re- lated to conjunctivitis.5 Approximately 70% of all
the palpebral part lines the inside of the eyelids (Figure 1). patients with acute conjunctivitis present to primary care and
Inflamma- tion or infection of the conjunctiva is known as urgent care.6
conjunctivitis and is characterized by dilatation of the conjunctival The prevalence of conjunctivitis varies according to the
vessels, resulting in hyperemia and edema of the conjunctiva, under- lying cause, which may be influenced by the patient’s age,
typically with associated discharge.1 as well as the season of the year. Viral conjunctivitis is the most
Conjunctivitis affects many people and imposes economic and common cause of infectious conjunctivitis both overall and in
social burdens. It is estimated that acute conjunctivitis affects 6 the adult population7-13 and is more prevalent in summer.14
mil- lion people annually in the United States.2 The cost of Bacterial con- junctivitis is the second most common cause7-
treating bac- terial conjunctivitis alone was estimated to be $377 9,12,13
and is respon- sible for the majority (50%-75%) of
million to $857 million per year.3 Many US state health cases in children 14 ; it is observed more frequently from
departments, irrespective of the underlying cause of December through April.14 Aller- gic conjunctivitis is the most
conjunctivitis, require students to be treated with topical frequent cause, affecting 15% to 40% of the population,15 and is
antibiotic eyedrops before returning to school.4 observed more frequently in spring and summer.14
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 Clinical Review & Education Review Review of Conjunctivitis Diagnosis and Treatment

Figure 1. Normal Conjunctival Anatomy

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 Eyelid Sclera

Limbus Bulbar
conjunctiva
Bulbar
conjunctiva

Cornea

Iris

Palpebral
conjunctiva
Palpebral
conjunctiva The conjunctiva is a thin membrane
covering the sclera (bulbar
conjunctiva, labeled with purple) and
SA GITT AL CROS S SE CTION
the inside of the eyelids (palpebral
conjunctiva, labeled with blue).

Figure 2. Suggested Algorithm for Clinical Approach to Suspected Acute referral. An algorithmic approach (Figure 2) using a focused
Conjunctivitis ocular history along with a penlight eye examination may be
helpful in di- agnosis and treatment. Because conjunctivitis and
Suspected acute conjunctivitis
(≤ 4 wk duration)
many other ocu- lar diseases can present as “red eye,” the
differential diagnosis of red eye and knowledge about the typical
Yes features of each disease in this category are important (Table 1).
Pain?

No
Yes
Photophobia?
Methods
No
The literature published through March 2013 was reviewed by
Blurred vision? search- ing PubMed, the ISI Web of Knowledge database, and the
blurred vision?
Cochrane
No Library. The following keywords were used: bacterial conjunctivitis,
No viral conjunctivitis, allergic conjunctivitis, treatment of bacterial
Hyperpurulent Gonococcal conjunctivitis
con-
Yes
Discharge? Mucopurulent Bacterial conjunctivitis tion was applied. Articles published between March 2003 and
(nongonococcal) March
Serous
Viral conjunctivitis 2013 were initially screened. After review of titles, abstracts, text,
and references for the articles, more were identified and screened.
No No Dry eye disease Articles and meta-analyses that provided evidence-based informa-
Itching?
Allergic conjunctivitis
tion about the cause, management, and treatment of various types
Yes
Itching?
in this review. The first study8 was published in 1982 and the last19
No in 2012. A level of evidence was assigned to the recommendations
Ophthalmology referral

tion grading system: “The strongest weight of evidence (A) is as-

signed if there are multiple randomized trials with large numbers
Conjunctivitis can be divided into infectious and noninfectious of patients. An intermediate weight (B) is assigned if there are a
causes. Viruses and bacteria are the most common infectious lim- ited number of randomized trials with small numbers of
causes. Noninfectious conjunctivitis includes allergic, toxic, and patients, careful analyses of non-randomized studies, or
cicatricial conjunctivitis, as well as inflammation secondary to observational reg- istries. The lowest rank of evidence (C) is
assigned when expert con- sensus is the primary basis for the
immune- mediated diseases and neoplastic processes.16 The
disease can also be classified into acute, hyperacute, and chronic recommendation.60
according to the mode of onset and the severity of the clinical
response.17 Further- more, it can be either primary or secondary to
systemic diseases such as gonorrhea, chlamydia, graft-vs-host How to Differentiate Conjunctivitis
disease, and Reiter syn- drome, in which case systemic of Different Origins
treatment is warranted.16
It is important to differentiate conjunctivitis from other sight- History and Physical Examination
threatening eye diseases that have similar clinical presentation and Focused ocular examination and history are crucial for making ap-
to make appropriate decisions about further testing, treatment, or propriate decisions about the treatment and management of any
eye

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Review of Conjunctivitis Diagnosis and Treatment Review Clinical Review & Education

Table 1. Selected Nonconjunctivitis Causes of Red Eyea

Differential Diagnosis Symptoms Penlight Examination Findings

Dry eye disease Burning and foreign-body sensation. Symptoms are usu- Bilateral redness
ally transient, worse with prolonged reading or watching
television because of decreased blinking. Symptoms are
worse in dry, cold, and windy environments because of
increased evaporation.
Blepharitis Similar to dry eyes Redness greater at the margins of eyelids
Uveitis Photophobia, pain, blurred vision. Symptoms are usually Decreased vision, poorly reacting pupils, constant eye
bilateral. pain radiating to temple and brow. Redness,
severe photophobia, presence of inflammatory cells in
the anterior chamber.
Angle closure glaucoma Headaches, nausea, vomiting, ocular pain, decreased Firm eye on palpation, ocular redness with limbal injec-
vision, light sensitivity, and seeing haloes around lights. tion. Appearance of a hazy/steamy cornea, moderately
Symptoms are usually unilateral. dilated pupils that are unreactive to light.
Carotid cavernous fistula Chronic red eye; may have a history of head trauma Dilated tortuous vessels (corkscrew vessels), bruits on
auscultation with a stethoscope
Endophthalmitis Severe pain, photophobia, may have a history of eye sur- Redness, pus in the anterior chamber, and
gery or ocular trauma photophobia
Cellulitis Pain, double vision, and fullness Redness and swelling of lids, may have restriction of the
eye movements, may have a history of preceding sinus-
itis (usually ethmoiditis)
Anterior segment tumors Variable Abnormal growth inside or on the surface of the eye
Scleritis Decreased vision, moderate to severe pain Redness, bluish sclera hue
Subconjunctival hemorrhage May have foreign-body sensation and tearing or be Blood under the conjunctival membrane
asymptomatic
a
Data are from Cronau et al18 and Leibowitz.1 The examination can be done by shining a penlight in the patient’s affected eye(s).
condition, including L
conjunctivitis. Eye a
discharge type and b
ocular s ymptoms can o
be used to r
determine the a
cause of the t
conjunctivitis.61,62 For o
example, a purulent or r
y
mucopurulent dis-
charge is often due to
bacterial I
conjunctivitis (Figure n
3A and Figure 3B), v
e
whereas a watery
s
discharge is more
t
characteristic of vi- ral i
conjunctivitis (Figure g
3C)61,62; itching is also a
associated with al- t
lergic i
conjunctivitis.49,63 o
However, the n
clinical presentation is s
often nonspecific. Obtaining conjunctival
Rely- ing on the type cultures is generally reserved
of discharge and for cases of sus- pected
patient symptoms does infectious neonatal
not al- ways lead to an conjunctivitis, recurrent
accurate diagnosis. conjunctivitis, conjunctivitis
Furthermore, scientific recalcitrant to therapy,
evi-correlating
dence correlating conjunctivitis presenting
ies the signs and symptoms of conjunctivitis with the
conjunctivitis signs
61
with severe purulent Infectious Conjunctivitis
un- derlying cause ; later, the same and authors cases
conducted a
and symptoms 61with discharge, Viral Conjunctivitis
prospective study and found suspicious for gonococcal of
that a combination or 3 signs—
the
ing of underlying
the eyelids, cause
lack isof itching, and no history16of conjunctivitis— Epidemiology, Cause, and Presentation
often
strongly lacking.
61
For chlamydial
predicted bacterial
infection.
conjunctivitis. Having both eyes mat- Viruses cause up to 80% of all cases of acute conjunctivitis.8-13,67
example, In-office rapid antigen
ter and theinlids a study
adhere ofin the morning was a stronger predictor for The rate of clinical accuracy in diagnosing viral conjunctivitis is
pa- tientsbacterial
with culture- testing is available for
positive culture result, and either itching or a previous less than 50% compared with laboratory confirmation.49 Many
positive adenoviruses and has 89%
bacterial made a positive bacterial culture result
epi- sode of conjunctivitis cases are misdiagnosed as bacterial conjunctivitis.49
conjunctivitis, sensitivity and up to 94%
less likely.64 In58% had type
addition, of discharge (purulent, mucus, or Between 65% and 90% of cases of viral conjunctivitis are
itch- ing, 65% had specificity.66 This test can
watery) or other symptoms were not specific to any particular caused by adenoviruses,49 and they produce 2 of the common
burning, and 35% had identify the viral causes of
class of conjunctivitis.64,65 clinical en- tities associated with viral conjunctivitis,
serous or no discharge conjunctivitis and prevent
Although in the primary care setting antibiotic
unnecessary an ocular examination
use. is pharyngoconjunctival fe- ver and epidemic keratoconjunctivitis.62
at
oftenall,64 illustrating
limited becausethe of lack of a slitlamp, useful information may ver is characterized by abrupt onset of high fever, pharyngitis, and
nonspecificity Thirty-six percent of
be obtained withof the penlight.
a simple The eye examination should fo- bilateral conjunctivitis, and by periauricular lymph node enlarge-
signsonand conjunctivitis cases are
cus the symptoms
assessmentofof the duevisual acuity, type and
to adenoviruses, of discharge,
one cor- ment, whereas epidemic keratoconjunctivitis is more severe and pre-
this
neal dis- ease.shape
opacity, In 2003,
and sizestudy
of the pupil, eyelid swelling, and sents with watery discharge, hyperemia, chemosis, and ipsilateral
apres-
large estimated that in-
ence meta-analysis
of proptosis. office rapid antigen testing lymphadenopathy.68 Lymphadenopathy is observed in up to 50%
failed to find any
clinical stud- could prevent 1.1 million
jama.com cases of inappropriate JAMA October 23/30, 2013 Volume 310, Number 16 1723
treatment with
antibiotics, potentially
saving $429 million
annually.2
 Clinical Review & Education Review Review of Conjunctivitis Diagnosis and Treatment

Table 2. Ophthalmic Therapies for Conjunctivitis

Type of Level of Evidence
Category Epidemiology Discharge Cause Treatment for Treatment
Acute bacterial 135 case per 10 000 Mucopurulent S aureus, Aminoglycosides
conjunctivitis population in US3 S epidermidis, H influenzae,
18.3%-57% of all acute S pneumoniae, Gentamicin B20-22
conjunctivitis7-9,12,13 S viridans, Moraxella spp Ointment: 4 ×/d for 1 wk
Solution: 1-2 drops 4 ×/d for 1 wk
Tobramycin ointment: 3 ×/d for 1 wk A23-30
Fluoroquinolones
Besifloxacin: 1 drop 3 ×/d for 1 wk A31-34
Ciprofloxacin ointment: 3 ×/d for 1 wk A24,28,29
Solution: 1-2 drops 4 ×/d for 1 wk
Gatifloxacin: 3 ×/d for 1 week B35
Levofloxacin: 1-2 drops 4 ×/d for 1 wk B36-38
Moxifloxacin: 3 ×/d for 1 wk A34,39,40
Ofloxacin: 1-2 drops 4 ×/d for 1 wk A37,38,41,42
Macrolides
Azithromycin: 2 ×/d for 2 d; then 1 drop A27,30,43,44
daily for 5 d
Erythromycin: 4 ×/d for 1 wk B45
Sulfonamides
Sulfacetamide ointment: 4 ×/d and at B22
bedtime for 1 wk
Solution: 1-2 drops every 2-3 h for 1 wk
Combination drops
Trimethoprim/polymyxin B: 1 or 2 drops A22,40,46
4 ×/d for 1 wk
Hyperacute NA Purulent Neisseria gonorrhoeae Ceftriaxone: 1 g IM once C16,47
bacterial
conjunctivitis Lavage of the infected eye C16
in adults Dual therapy to cover chlamydia is indicated C48
Viral 9%-80.3% of all acute Serous Up to 65% are due to Cold compress
conjunctivitis conjunctivitis8-13 adenovirus strains49 Artificial tears C16,50
Antihistamines
Herpes zoster NA Variable Herpes zoster virus Oral acyclovir 800 mg: 5 ×/d for 7-10 d C16
virus
Oral famciclovir 500 mg: 3 ×/d for 7-10 d C16
Oral valacyclovir 1000 mg: 3 ×/d for 7-10 d C16
Herpes simplex 1.3-4.8 of all acute Variable Herpes simplex virus Topical acyclovir: 1 drop 9 ×/d C16
virus conjunctivitis9-12
Oral acyclovir 400 mg: 5 ×/d for 7-10 d C16
Oral valacyclovir 500 mg: 3 ×/d for 7-10 d C16
Adult inclusion 1.8%-5.6% of all acute Variable Chlamydia trachomatis Azithromycin 1 g: orally once B16,51
conjunctivitis conjunctivitis5,8-11
Doxycycline 100 mg: orally 2 ×/d for 7 d B16,51
Allergic 90% of all allergic Serous or Pollens Topical antihistamines
conjunctivitis conjunctivitis15; mucoid
up to 40% of Azelastine 0.05%: 1 drop 2 ×/d A52
population may be Emedastine 0.05%: 1 drop 4 ×/d A52
affected15
Topical mast cell inhibitors
Cromolyn sodium 4%: 1-2 drops every 4-6 h A52
Lodoxamide 0.1%: 1-2 drops 4 ×/d A52
Nedocromil 2%: 1-2 drops 2 ×/d A52
NSAIDs
Ketorolac: 1 drop 4 ×/d B53,54
Vasoconstrictor/antihistamine
Naphazoline/pheniramine: 1-2 drops up to B55
4 ×/d
Combination drops
Ketotifen 0.025%: 1 drop 2-3 ×/d A56,57
Olopatadine 0.1%: 1 drop 2 ×/d A58,59
Abbreviations: IM, intramuscularly; NA, not available; NSAIDs, nonsteroidal anti-inflammatory drugs.

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Review of Conjunctivitis Diagnosis and Treatment Review Clinical Review & Education
of viral conjunctivitis cases and is more prevalent in viral of cases, respectively.72 Patients with suspected eyelid or eye in-
conjuncti- vitis compared with bacterial conjunctivitis.49 volvement or those presenting with Hutchinson sign (vesicles at
the tip of the nose, which has high correlations with corneal
Prevention and Treatment involve- ment) should be referred for a thorough ophthalmic
Viral conjunctivitis secondary to adenoviruses is highly contagious, evaluation. Treatment usually consists of a combination of oral
and the risk of transmission has been estimated to be 10% to antivirals and topi- cal steroids.73
50%.6,14
The virus spreads through direct contact via contaminated Bacterial Conjunctivitis
fingers, medical instruments, swimming pool water, or personal Epidemiology, Cause, and Presentation
items; in one study, 46% of infected people had positive cultures The incidence of bacterial conjunctivitis was estimated to be 135
grown from swabs of their hands.69 Because of the high rates of in
transmission, hand washing, strict instrument disinfection, and 10 000 in one study.3 Bacterial conjunctivitis can be contracted
isolation of the in- fected patients from the rest of the clinic has di- rectly from infected individuals or can result from abnormal
been advocated.70 In- cubation and communicability are prolif- eration of the native conjunctival flora.17 Contaminated
estimated to be 5 to 12 days and fingers,14 ocu- logenital spread,16 and contaminated fomites48 are
10 to 14 days, respectively.14 common routes of transmission. In addition, certain conditions
Although no effective treatment exists, artificial tears, topical such as compro- mised tear production, disruption of the natural
antihistamines, or cold compresses may be useful in alleviating epithelial barrier, abnormality of adnexal structures, trauma,
some of the symptoms (Table 2).16,50 Available antiviral and immunosup- pressed status predispose to bacterial
medications are not useful16,50 and topical antibiotics are not conjunctivitis.16 The most common pathogens for bacterial
indicated.18 Topical an- tibiotics do not protect against secondary conjunctivitis in adults are staphy- lococcal species, followed by
infections, and their use may complicate the clinical presentation Streptococcus pneumoniae and Hae- mophilus influenzae.41 In
by causing allergy and tox- icity, leading to delay in diagnosis of children, the disease is often caused by H influenzae, S
other possible ocular diseases.49 pneumoniae, and Moraxella catarrhalis.41 The course of the
Use of antibiotic eyedrops can increase the risk of spreading the disease usually lasts 7 to 10 days (Figure 3).62
in- fection to the other eye from contaminated droppers.49
Increased resistance is also of concern with frequent use of Table 3. Evidence-Based Recommendations in
antibiotics.6 Pa- tients should be referred to an ophthalmologist if Conjunctivitis
symptoms do not resolve after 7 to 10 days because of the risk of Level of
complications.1
Recommendation Evidence
Herpes Conjunctivitis Topical antibiotics are effective in reducing the duration A19
of conjunctivitis.
Herpes simplex virus comprises 1.3% to 4.8% of all cases of acute
Observation is reasonable in most cases of bacterial
conjunctivitis.9-12 Conjunctivitis caused by the virus is usually uni- conjunctivitis (suspected or confirmed) because they often A41
lateral. The discharge is thin and watery, and accompanying resolve spontane- ously and no treatment is necessary.
vesicu- lar eyelid lesions may be present. Topical and oral It is reasonable to use any broad-spectrum antibiotics for
treating bacterial conjunctivitis. A19,41
antivirals are rec- ommended (Table 2) to shorten the course of
In allergic conjunctivitis, use of topical antihistamines and
the disease.16 Topical corticosteroids should be avoided because mast cell stabilizers is recommended. A52
they potentiate the vi- rus and may cause harm.16,71 Good hand hygiene can be used to decrease the spread of
acute viral conjunctivitis.
Herpes zoster virus, responsible for shingles, can involve C16
Bacterial cultures can be useful in cases of severely
ocu- lar tissue, especially if the first and second branches of the purulent conjunctivitis or cases that are recalcitrant to
trigemi- nal nerve are involved. Eyelids (45.8%) are the most therapy. C16
common site It may be helpful to treat viral conjunctivitis with artificial
tears, topical antihistamines, or cold compresses. C16
of ocular involvement, followed by the conjunctiva (41.1%).72
Cor-
neal complication and uveitis may be present in 38.2% and 19.1% Topical steroids are not recommended for bacterial conjunctivitis. C65

Figure 3. Characteristic Appearance of Bacterial and Viral Conjunctivitis

A Bacterial conjunctivitis B Hyperacute bacterial conjunctivitis C Viral conjunctivitis

A, Bacterial conjunctivitis characterized by mucopurulent discharge and bacterial conjunctivitis secondary to gonorrhea. C, Intensely
conjunctival hyperemia. B, Severe purulent discharge seen in hyperacute hyperemic
response with thin, watery discharge characteristic of viral conjunctivitis. Ophthalmology.
Images reproduced with permission: © 2013 American Academy of

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Clinical Review & Education Review Review of Conjunctivitis Diagnosis and Treatment
 Hyperacute bacterial conjunctivitis presents with a severe terns, and cost. Initial therapy for acute nonsevere bacterial con-
copious purulent discharge and decreased vision (Figure 3). There junctivitis is listed in Table 2.
is often accompanying eyelid swelling, eye pain on palpation, and
preauricular adenopathy. It is often caused by Neisseria gonor- Alternatives to Immediate Antibiotic Therapy | To our knowledge,
rhoeae and carries a high risk for corneal involvement and subse- no studies have been conducted to evaluate the efficacy of ocular
quent corneal perforation.17 Treatment for hyperacute conjunctivi- de- congestant, topical saline, or warm compresses for treating
tis secondar y to N gonorrhoeae consists of intramuscular bacte- rial conjunctivitis.41 Topical steroids should be avoided
ceftriaxone, and concurrent chlamydial infection should be man- because of the risk of potentially prolonging the course of the
aged accordingly.47 disease and po- tentiating the infection.16
Chronic bacterial conjunctivitis is used to describe any
conjunc- tivitis lasting more than 4 weeks, with Staphylococcus Summary of Recommendations
aureus, Mo- raxella lacunata, and enteric bacteria being the most for Managing Bacterial Conjunctivitis
common causes in this setting62; ophthalmologic consultation In conclusion, benefits of antibiotic treatment include quicker re-
should be sought for management. covery, decrease in transmissibility,49 and early return to school.4
Signs and symptoms include red eye, purulent or mucopuru- Simultaneously, adverse effects are absent if antibiotics are not
lent discharge, and chemosis (Figure 3).17 The period of incubation used in uncomplicated cases of bacterial conjunctivitis.
and communicability is estimated to be 1 to 7 days and 2 to 7 Therefore, no treatment, a wait-and-see policy, and immediate
days, respectively.14 Bilateral mattering of the eyelids and treatment all ap- pear to be reasonable approaches in cases of
adherence of the eyelids, lack of itching, and no history of uncomplicated con- junctivitis. Antibiotic therapy should be
conjunctivitis are strong positive predictors of bacterial considered in cases of pu- rulent or mucopurulent conjunctivitis
conjunctivitis.64 Severe purulent dis- charge should always be and for patients who have distinct discomfort, who wear contact
cultured and gonococcal conjunctivitis should be considered lenses,14,18 who are immu- nocompromised, and who have
(Figure 3B).16 Conjunctivitis not responding to standard antibiotic suspected chlamydial and gono- coccal conjunctivitis.
therapy in sexually active patients warrants a chlamydial
evaluation.18 The possibility of bacterial keratitis is high Special Topics in Bacterial
in contact lens wearers, who should be treated with topical Conjunctivitis
antibiotics14 and referred to an ophthalmologist. A patient wearing Methicillin-Resistant S aureus Conjunctivitis
contact lenses should be asked to immediately remove them.65 It is estimated that 3% to 64% of ocular staphylococcal
infections are due to methicillin-resistant S aureus conjunctivitis;
Use of Antibiotics in Bacterial Conjunctivitis this condi- tion is becoming more common and the organisms are
At least 60% of cases of suspected or culture-proven acute bacte- resistant to many antibiotics.76 Patients with suspected cases
rial conjunc tivitis are self-limiting within 1 t o 2 weeks need to be re- ferred to an ophthalmologist and treated with
of presentation.14 Although topical antibiotics reduce the duration fortified vancomycin.77
of the disease, no differences have been observed in outcomes
be- tween treatment and placebo groups. In a large meta-analysis,19 Chlamydial Conjunctivitis
con- sisting of a review of 3673 patients in 11 randomized clinical It is estimated that 1.8% to 5.6% of all acute conjunctivitis is
trials, there was an approximately 10% increase in the rate of caused by chlamydia,5,8-11 and the majority of cases are unilateral
clinical im- provement compared with that for placebo for and have concurrent genital infection.1 Conjunctival hyperemia,
patients who re- ceived either 2 to 5 days or 6 to 10 days of mucopuru- lent discharge, and lymphoid follicle formation51 are
antibiotic treatment com- pared with the placebo. No serious sight- hallmarks of this condition. Discharge is often purulent or
threatening outcomes were reported in any of the placebo mucopurulent.18 How- ever, patients more often present with
groups.74 Some highly virulent bac- teria, such as S pneumoniae, mild symptoms for weeks to months. Up to 54% of men and 74%
N gonorrhoeae, and H influenzae, can penetrate an intact host of women have concurrent geni- tal chlamydial infection.78 The
defense more easily and cause more seri- ous damage.17 disease is often acquired via oculo- genital spread or other
Topical antibiotics seem to be more effective in patients who intimate contact with infected individuals; in newborns the eyes
have positive bacterial culture results. In a large systemic review, can be infected after vaginal delivery by in- fected mothers.16
they were found to be effective at increasing both the clinical and Treatment with systemic antibiotics such as oral azithromycin and
micro- biological cure rate in the group of patients with culture- doxycycline is efficacious (Table 2); patients and their sexual
proven bac- terial conjunctivitis, whereas only an improved partners must be treated and a coinfection with gon- orrhea must
microbial cure rate was observed in the group of patients with be investigated. No data support the use of topical an- tibiotic
clinically suspected bac- terial conjunctivitis.67 Other studies therapy in addition to systemic treatment.16 Infants with chla-
found no significant differ- ence in clinical cure rate when the mydial conjunctivitis require systemic therapy because more than
frequencies of the administered antibiotics were slightly 50% can have concurrent lung, nasopharynx, and genital tract
changed.41,75 infection.16

Choices of Antibiotics | All broad-spectrum antibiotic eyedrops Gonococcal Conjunctivitis

seem in general to be effective in treating bacterial conjunctivitis. Conjunctivitis caused by N gonorrhoeae is a frequent source of
There are no significant differences in achieving clinical cure hy- peracute conjunctivas in neonates and sexually active adults
between any of the broad-spectrum topical antibiotics. Factors and young adolescents. 17 Treatment consists of both topical and
that influence an- tibiotic choice are local availability, patient oral an- tibiotics. Neisseria gonorrhoeae is associated with a high
allergies, resistance pat- risk of cor- neal perforation.65
1726 JAMA October 23/30, 2013 Volume 310, Number 16 jama.com
Review of Conjunctivitis Diagnosis and Treatment Review Clinical Review & Education

Conjunctivitis Secondary to Trachoma grade carotid cavernous fistula can present with chronic conjuncti-
Trachoma is caused by Chlamydia trachomatis subtypes A through vitis recalcitrant to medical therapy, which, if left untreated, can
C and is the leading cause of blindness, affecting 40 million people lead to death.
worldwide in areas with poor hygiene.79,80 Mucopurulent dis-
charge and ocular discomfort may be the presenting signs and Ominous Signs
symp- toms in this condition. Late complications such as scarring of As recommended by the American Academy of Ophthalmology,16
the conjunctiva,
lid, eye- and cornea may lead to loss of vision. Treatment with patients with conjunctivitis who are evaluated by nonophthalmolo-
a single dose of oral azithromycin (20 mg/kg) is effective. Patients gist health care practitioners should be referred promptly to an oph-
may also be treated with topical antibiotic ointments for 6 weeks thalmologist if any of the following develops: visual loss, moderate
(ie, tetracycline or erythromycin). Systemic antibiotics other than or severe pain, severe purulent discharge, corneal involvement, con-
azithromycin, such as tetracycline or erythromycin for 3 weeks, may junctival scarring, lack of response to therapy, recurrent episodes of
be used alternatively.79,80 conjunctivitis, or history of herpes simplex virus eye disease. In ad-
dition, the following patients should be considered for referral: con-
tact lens wearers, patients requiring steroids, and those with pho-
tophobia. Patients should be referred to an ophthalmologist if there
Noninfectious Conjunctivitis
is no improvement after 1 week.1
Allergic Conjunctivitis
Prevalence and Cause Importance of Not Using Antibiotic/Steroid
Allergic conjunctivitis is the inflammatory response of the conjunc- Combination Drops
tiva to allergens such as pollen, animal dander, and other environ- Steroid drops or combination drops containing steroids should not
mental antigens15 and affects up to 40% of the population in the be used routinely. Steroids can increase the latency of the adeno-
United States15; only about 10% of individuals with allergic conjunc- viruses, therefore prolonging the course of viral conjunctivitis. In ad-
tivitis seek medical at tention, and the entity i s o f ten dition, if an undiagnosed corneal ulcer secondary to herpes, bacte-
underdiagnosed.81 Redness and itching are the most consistent ria, or fungus is present, steroids can worsen the condition, leading
symptoms.15 Seasonal allergic conjunctivitis comprises 90% of all to corneal melt and blindness.
allergic conjunctivitis in the United States.82

Treatment
Conclusions
Treatment consists of avoidance of the offending antigen 52 and
use of saline solution or artificial tears to physically dilute and Approximately 1% of all patient visits to a primary care clinician are
remove the allergens.15 Topical decongestants, antihistamines,52 conjunctivitis related, and the estimated cost of the bacterial con-
mast cell stabilizers,52 nonsteroidal anti-inflammatory drugs,53,54 junctivitis alone is $377 million to $857 million annually.3,5 Relying
and corticosteroids 82 may be indicated. In a large systemic on the signs and symptoms often leads to an inaccurate diagnosis.
review, both antihistamines and mast cell stabilizers were Nonherpetic viral conjunctivitis followed by bacterial conjunctivi-
superior to placebo in reducing the symptoms of allergic conjunc- tis is the most common cause for infectious conjunctivitis.7-13 Aller-
tivitis; researchers also found that antihistamines were superior gic conjunctivitis affects nearly 40% of the population, but only a
to mast cell stabilizers in providing shor t-term benef its. 52 small proportion seeks medical care.15,81 The majority of viral con-
Long-term use of the antihistamine antazoline and the vasocon- junctivitis cases are due to adenovirus.49 There is no role for the use
strictor naphazoline should be avoided because they both can of topical antibiotics in viral conjunctivitis, and they should be
cause rebound hyperemia.52 Steroids should be used with cau- avoided of adverse treatment effects.6,49 Using a rapid antigen test
because
tion and judiciously. Topical steroids are associated with forma- to diagnose viral conjunctivitis and avoid inappropriate use of anti-
tion of cataract and can cause an increase in eye pressure, leading biotics is an appropriate strategy.66 Bacterial pathogens are iso-
to glaucoma. lated in only 50% of cases of suspected conjunctivitis,18 and at least
60% of bacterial conjunctivitis (clinically suspected or culture
Drug-, Chemical-, and Toxin-Induced Conjunctivitis proven) is self-limited without treatment.14 Cultures are useful in
A variety of topical medications such as antibiotic eyedrops, topi- cases that do not respond to therapy, cases of hyperacute conjunc-
cal antiviral medications, and lubricating eyedrops can induce aller- tivitis, and suspected chlamydial conjunctivitis.16 Treatment with
gic conjunctival responses largely because of the presence of ben- topical antibiotics is usually recommended for contact lens wear-
zalkonium chloride in eye drop preparations.83 Cessation of receiving ers, those with mucopurulent discharge and eye pain, suspected
the offending agent leads to resolution of symptoms.16 cases of chlamydial and gonococcal conjunctivitis, and patients with
preexisting ocular surface disease.14,18 The advantages of antibi-
Systemic Diseases Associated With Conjunctivitis otic use include early resolution of the disease,19 early return to
A variety of systemic diseases, including mucous membrane pem- work or school,4,14 and the possibility of decreased complications
phigoid, Sjögren syndrome, Kawasaki disease,84 Stevens-Johnson conjunctivitis.14 The majority of cases of allergic conjunctivitis are
syndrome,85 and carotid cavernous fistula,86 can present with signs due to seasonal allergies.82 Antihistamines, mast cell inhibitors, and
and symptoms of conjunctivitis, such as conjunctival redness and topical steroids (in selected cases) are indicated for treating aller-
discharge. Therefore, the above causes should be considered in pa- gic conjunctivitis.82 Steroids must be used judiciously and only af-
tients presenting with conjunctivitis. For example, patients with low- ter a thorough ophthalmologic examination has been performed to

jama.com JAMA October 23/30, 2013 Volume 310, Number 16 1727

Clinical Review & Education Review Review of Conjunctivitis Diagnosis and Treatment
rule out herpetic infection or corneal involvement, both of which Physicians must be vigilant to not overlook sight-threatening
can worsen with steroids.16,71 conditions with similarities to conjunctivitis, as summarized in Table
1.

ARTICLE INFORMATION by herpes simplex virus type 1. Br J Ophthalmol. 27. Bremond-Gignac D, Mariani-Kurkdjian P,
Conflict of Interest Disclosures: All authors have 2000;84(9):968-972. Beresniak A, et al. Efficacy and safety of
completed and submitted the ICMJE Form for 12. Woodland RM, Darougar S, Thaker U, et al. azithromycin 1.5% eye drops for purulent bacterial
Disclosure of Potential Conflicts of Interest and Causes of conjunctivitis and keratoconjunctivitis in conjunctivitis in pediatric patients. Pediatr Infect
none were reported. Karachi, Pakistan. Trans R Soc Trop Med Hyg. Dis J. 2010;29(3):222-226.
Funding/Support: This work was supported by 1992;86(3):317-320. 28. Leibowitz HM. Antibacterial effectiveness of
National Institutes of Health (NIH) grant 13. Fitch CP, Rapoza PA, Owens S, et al. ciprofloxacin 0.3% ophthalmic solution in the
P30-EY016665 (Core Grant for Vision Research) and Epidemiology and diagnosis of acute conjunctivitis treatment of bacterial conjunctivitis. Am J
an unrestricted department award from Research to at an inner-city hospital. Ophthalmology. Ophthalmol. 1991;112(4)(suppl):29S-33S.
Prevent Blindness. The project was also supported 1989;96(8):1215-1220. 29. Gross RD, Hoffman RO, Lindsay RN. A
by the Clinical and Translational Science Award comparison of ciprofloxacin and tobramycin in
14. Høvding G. Acute bacterial conjunctivitis. Acta
program through the NIH National Center for bacterial conjunctivitis in children. Clin Pediatr
Ophthalmol. 2008;86(1):5-17.
Advancing Translational Sciences, grant (Phila). 1997;36(8):435-444.
UL1TR000427. 15. Bielory BP, O’Brien TP, Bielory L. Management
of seasonal allergic conjunctivitis: guide to therapy. 30. Denis F, Chaumeil C, Goldschmidt P, et al.
Role of the Sponsor: The sponsors played no role in Micro- biological efficacy of 3-day treatment with
Acta Ophthalmol. 2012;90(5):399-407.
the design and conduct of the study; collection, man- azithromy- cin 1.5% eye-drops for purulent bacterial
agement, analysis, and interpretation of the data; 16. American Academy of Ophthalmology; conjunctivi- tis. Eur J Ophthalmol. 2008;18(6):858-
preparation, review, or approval of the manuscript; Cornea/External Disease Panel. Preferred Practice 868.
and decision to submit the manuscript for Pattern Guidelines: Conjunctivitis-Limited
Revision. San Francisco, CA: American Academy 31. Silverstein BE, Allaire C, Bateman KM, et al.
publication.
of Ophthalmology; 2011. Efficacy and tolerability of besifloxacin ophthalmic
Correction: This article was corrected on suspension 0.6% administered twice daily for 3
December 5, 2013, to correct the dosage of 17. Mannis MJ, Plotnik RD. Bacterial days in the treatment of bacterial conjunctivitis: a
acyclovir for herpes in Table 2 and to update the conjunctivitis. In: Tasman W, Jaeger EA, eds. multicenter, randomized, double-masked,
algorithm in Figure 2 to include viral Duanes Ophthalmology on CD-ROM. Lippincott vehicle-controlled, parallel-group study in adults
conjunctivitis. Williams & Wilkins; 2006. and children. Clin Ther. 2011;33(1):13-26.
Submissions:We encourage authors to submit 18. Cronau H, Kankanala RR, Mauger T. 32. Karpecki P, Depaolis M, Hunter JA, et al.
papers for consideration as a Review. Please Diagnosis and management of red eye in primary Besifloxacin ophthalmic suspension 0.6% in
contact Mary McGrae McDermott, MD, at mdm608 care. Am Fam Physician. 2010;81(2):137-144. patients with bacterial conjunctivitis: a multicenter,
@northwestern.edu. 19. Sheikh A, Hurwitz B, van Schayck CP, McLean prospective, randomized, double-masked,
S, Nurmatov U. Antibiotics versus placebo for acute vehicle-controlled, 5-day efficacy and safety study.
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