Neonatal conjunctivitis, also known as ophthalmia neonatorum, presents during the first month of life. It may be aseptic or septic.
Aseptic neonatal conjunctivitis most often is a chemical conjunctivitis that is induced by silver nitrate solution, which is used at birth for Crede prophylaxis of infectious conjunctivitis. Chemical conjunctivitis is becoming less common owing to the use of erythromycin ointment or povidone iodide in place of silver nitrate solution for the prophylaxis of infectious conjunctivitis. (See Etiology and Treatment.)
Bacterial and viral infections are major causes of septic neonatal conjunctivitis, with Chlamydia being the most common infectious agent. Infants may acquire these infective agents as they pass through the birth canal during the birth process. (The effects of gonococcal conjunctivitis are seen in the images below.) (See Etiology.)
View Image | Severe purulent discharge and eyelid edema in a newborn with gonococcal conjunctivitis (confirmed with Gram stain and culture). |
View Image | Cloudy cornea without ulcer in neonatal gonococcal conjunctivitis. |
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The conjunctiva (a thin translucent mucous membrane) can be divided into palpebral, bulbar, and fornical, based on the location. The conjunctiva contains nonkeratinizing, squamous epithelium and a thin, richly vascularized substantia propria containing lymphatic vessels and cells, such as lymphocytes, plasma cells, mast cells, and macrophages. The conjunctiva also has accessory lacrimal glands and goblet cells.
The pathology of neonatal conjunctivitis is influenced by the anatomy of the conjunctival tissues in the newborn. The inflammation of the conjunctiva may cause blood vessel dilation, potentially dramatic chemosis, and excessive secretion. This infection tends to be more serious in neonates owing to their lack of immunity, lack of lymphoid tissue in the conjunctiva, and absence of tears at birth.
Educate parents or care providers to wash their hands frequently to prevent transmission of neonatal conjunctivitis. Educate pregnant women on the importance of regular examinations to detect and treat sexually transmitted infections such as herpes simplex, gonorrhea, and chlamydia in order to decrease the incidence of neonatal conjunctivitis.
For patient education information, see the Eye and Vision Center, as well as Pinkeye.
The etiology of neonatal conjunctivitis can be chemical or microbial. Although several noninfectious and infectious agents can inflame the conjunctiva, the most common causes of neonatal conjunctivitis are silver nitrate solution and chlamydial, gonococcal, staphylococcal, and herpetic infections.
Crede's method of instilling a drop of 2% aqueous solution of silver nitrate into a newborn's eyes was first published in 1881 and significantly advanced the prevention of neonatal conjunctivitis.[1]
Silver nitrate is a surface-active chemical that facilitates agglutination and inactivation of gonococci. Ironically, silver nitrate was later found to be toxic to the conjunctiva, particularly in higher concentrations, potentially causing a sterile neonatal conjunctivitis.
Chlamydia trachomatis is an obligate intracellular parasite and has been identified as the most common infectious cause of neonatal conjunctivitis.[2]
The reservoir of the organism is the maternal cervix or urethra. Infants who are born to infected mothers are at high risk (approximately 25%-50%) of developing an infection.[3] Chlamydial pneumonitis may also accompany neonatal conjunctivitis.
Neisseria gonorrhoeae is a gram-negative diplococcus and is potentially the most dangerous and virulent infectious cause of neonatal conjunctivitis. As with chlamydia, maternal cervical and urethral mucosa provide a reservoir for N gonorrhoeae, which is acquired during birth.
Gonococci can penetrate intact epithelial cells and divide rapidly inside them. Diagnostic Gram or Giemsa stain smears obtained from genitourinary or ocular mucosal scrapings reveal characteristic gram-negative intracellular diplococci.
Gonococcal conjunctivitis must be absolutely excluded in every case of neonatal conjunctivitis to prevent potentially blinding corneal and conjunctival complications.
The most commonly identified gram-positive organisms include Staphylococcus aureus,Streptococcus pneumoniae,Streptococcus viridans, and Staphylococcus epidermidis. These bacteria make up 30-50% of all cases of infectious neonatal conjunctivitis.[4]
Gram-negative organisms, such as Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Proteus, Enterobacter, and Pseudomonas species, also have been implicated. There has been one reported case of Eikenella corrodens neonatal conjunctivitis.[5]
Infants of low birth weight and low gestational age with clinical signs of conjunctivitis in the neonatal intensive care unit (NICU) should be evaluated and treated for a gram-negative etiology.[6]
Herpes simplex virus (HSV) is a rare cause of neonatal keratoconjunctivitis, found in less than 1% of cases,[4] and can be associated with a generalized herpes simplex infection.
Most infants with such an infection acquire the disease during the birth process. Caesarean delivery is strongly considered when active maternal genital disease is recognized at term since the risk of transmitting HSV to the neonate during vaginal delivery is 25-60%.[7]
The incidence of infectious neonatal conjunctivitis ranges from 1-2%, depending on the socioeconomic character of the area.
The epidemiology of neonatal conjunctivitis changed when silver nitrate solution was introduced in the 1800s to prevent gonococcal ophthalmia.
Chlamydia is the most common infectious agent that causes ophthalmia neonatorum in the United States, where 2%-40% of neonatal conjunctivitis cases are caused by Chlamydia.[3]
In contrast, the incidence of gonococcal ophthalmia neonatorum has been reduced dramatically and causes less than 1% of cases of neonatal conjunctivitis.[8]
As in the United States, the incidence of ophthalmia neonatorum in many other countries decreased after silver nitrate solution came into general use.
In Europe, the incidence fell from 10% of births to less than 1%.
The rates of neonatal conjunctivitis vary in different parts of the world. In one hospital in Pakistan, the incidence of neonatal conjunctivitis was reported at 17%.[9]
No published information is available on race- or sex-related differences in the incidence of neonatal conjunctivitis.
Neonatal conjunctivitis usually responds to appropriate treatment, and the prognosis generally is good.
Antibiotics have significantly altered the prognosis of neonatal conjunctivitis, especially with Neisseria gonorrhoeae infection.
Mortality associated with neonatal conjunctivitis is due to systemic involvement of the infectious agent. No published information is available on mortality.
If untreated, peripheral corneal ulceration may occur in N gonorrhoeae infection and rapidly progress to corneal perforation.
When unrecognized and not immediately treated, Pseudomonas infection may lead to endophthalmitis and subsequent death.
Pneumonia has been reported in 10-20% of infants with chlamydial conjunctivitis.[10]
HSV keratoconjunctivitis can cause corneal scarring and ulceration. Additionally, disseminated HSV infection often includes central nervous system involvement.[7]
Chemical conjunctivitis secondary to silver nitrate solution application usually occurs in the first day of life, disappearing spontaneously within 2-4 days.
Gonococcal conjunctivitis tends to occur 2-7 days after birth but can present later.[4]
The onset of chlamydial conjunctivitis is usually later than gonococcal conjunctivitis; the incubation period is 5-14 days.
The expected incubation period for other nongonococcal, nonchlamydial conjunctivitis is also 5-14 days.[4]
Herpetic conjunctivitis usually occurs within the first 2 weeks after birth and has an incubation period of approximately 6-14 days.[4]
Gonococcal conjunctivitis tends to be more severe than other causes of ophthalmia neonatorum. The classic presentation is severe bilateral purulent conjunctivitis.
Corneal involvement, including diffuse epithelial edema, limbal ulceration adjacent to severe conjunctival chemosis, and diffuse opacification, may progress to perforation of the cornea and endophthalmitis.
Patients also may have systemic manifestations, including rhinitis, stomatitis, arthritis, meningitis, anorectal infection, and septicemia.
The presentation of chlamydial conjunctivitis may range from mild hyperemia with scant mucoid discharge to eyelid swelling, chemosis, and pseudomembrane formation.
Blindness, although rare and much slower to develop than in gonococcal conjunctivitis, is generally not due to corneal involvement as in gonococcal conjunctivitis. Instead, eyelid scarring and corneal pannus can gradually progress to central corneal opacification by mechanisms reminiscent of trachoma.
A follicular reaction does not occur, because newborns have no requisite lymphoid tissue present in the conjunctiva.
Like gonococcal conjunctivitis, chlamydial conjunctivitis also may be associated with extraocular involvement, including pneumonitis, otitis, and pharyngeal and rectal colonization.
Neonatal conjunctivitis due to other microbial agents is usually milder.
Herpes simplex keratoconjunctivitis often presents in infants with generalized herpes simplex infections, characterized by corneal epithelial involvement or vesicles on the periocular skin. Serious systemic complications, such as encephalitis, may also occur in these neonates owing to their poor immunologic response.
Presentations for different organisms may vary. Typical findings may include erythema and edema of the eyelids and palpebral conjunctiva and/or purulent eye discharge during the external eye exam. A Gram stain conjunctival smear should be performed in all cases. Eyelid edema and purulent discharge are seen in the image below.
View Image | Severe purulent discharge and eyelid edema in a newborn with gonococcal conjunctivitis (confirmed with Gram stain and culture). |
The clinical picture of chemical conjunctivitis is mild with transient tearing and conjunctival injection.
If the 1% silver nitrate used for neonatal conjunctivitis is provided in a large bottle, the solution can evaporate or settle, thereby becoming more concentrated over time. More concentrated silver nitrate solution may result in more severe responses, including, lid edema, chemosis, exudate, membranes or pseudomembranes, and permanent cicatricial damage to the conjunctiva or the cornea. This problem is obviated by using sealed, single-use ampules. Chemical conjunctivitis is becoming less common because of the substitution of alternative agents such as erythromycin ointment, tetracycline ointment, or povidone iodide in place of silver nitrate.
Patients typically present with unilateral or bilateral watery discharge, which may become more copious and purulent later.
Although most cases are mild and self-limited, chlamydial conjunctivitis occasionally may be severe. Pseudomembranes, thickened palpebral conjunctiva, significant peripheral pannus, and corneal opacification may be present.
Gonococcal conjunctivitis is the most serious form of neonatal conjunctivitis with the most rapid onset, usually occurring 24-48 hours following birth. Typically, patients develop a hyperacute conjunctivitis, associated with marked lid edema, chemosis, and purulent discharge.
A conjunctival membrane may be present.
Corneal ulceration may occur, particularly in the periphery, where massive limbal conjunctival chemosis traps inflammatory mediators and organisms, with rapid progression to perforation if treatment is delayed.
Various organisms, including gram-positive and gram-negative bacteria, have been identified in neonatal conjunctivitis.
Classic clinical pictures are lid edema, conjunctival injection, chemosis, and discharge, which are variable and often indistinguishable from signs of other etiologies.
Although rarely implicated in neonatal conjunctivitis, Pseudomonas can lead to devastating consequences, such as rapid progression to corneal ulceration and perforation. If left untreated, Pseudomonas keratitis even can lead to endophthalmitis and subsequent death.
This type of neonatal conjunctivitis typically occurs within the first 2 weeks after birth.
Ocular involvement may follow systemic or central nervous system herpes infection, as well as vesicular lesions on the skin or lid margins.
Patients may present with nonspecific lid edema, moderate conjunctival injection, and a nonpurulent and often serosanguineous discharge, which may be unilateral or bilateral.
Microdendrites or geographic ulcers, rather than typical dendrites as seen in adults, are the most typical signs of herpetic keratitis in newborns.
Conjunctival membrane may be present.
Laboratory studies for neonatal conjunctivitis should include the following:
Bacterial cultures on blood and chocolate agar are indicated in every case of neonatal conjunctivitis and remain the criterion standard despite newer diagnostic methods.
Since Chlamydia bacteria are obligate intracellular organisms, the culture specimens need to contain epithelial cells and not just exudative material. PCR is generally accepted as the most useful test for chlamydial conjunctivitis owing to its high sensitivity.[11]
In cases in which gonorrhea is suspected, the agar should be inoculated immediately since Ngonorrhoeae is very sensitive to moisture and temperature changes.
Laboratory evaluation for the presence of HSV infection is indicated if a corneal epithelial defect is present, if vesicles are present on the eyelids or other parts of the body, and if the diagnosis cannot be made on ocular examination. The presence of HSV in tissue culture remains the criterion standard in the diagnosis of HSV, despite a high false-negative rate. HSV infections may be more rapidly diagnosed with PCR, and PCR testing for HSV is more sensitive than viral culture.[11] Laboratory evaluation for suspected HSV becomes more important in neonatal disease because the clinical presentation may be highly atypical in an immunologically immature newborn.
Cytologic findings for various forms of conjunctivitis are as follows:
Nucleic acid amplification tests such as polymerase chain reaction (PCR) and transcription-mediated amplification (TMA) are more sensitive than culture in detecting chlamydial and gonorrheal organisms.[8, 3]
PCR assays may have a higher sensitivity and similar specificity in diagnosing neonatal chlamydial conjunctivitis, compared with conventional methods.[12]
PCR for HSV from conjunctival scrapings has high sensitivity and specificity, but it is expensive, not always readily available, and is usually reserved for the diagnosis of encephalitis. Direct florescent antibody (DFA) studies are useful for rapid detection, have high sensitivity and specificity, and can be used to type the virus.[7]
Specific treatment is available for each cause of neonatal conjunctivitis. Preliminary presumptive treatment pending culture confirmation should be based on the clinical picture and the findings on Gram, Giemsa, and Papanicolaou stains.
Prior to birth, consider the risk of transmission of chlamydial, gonococcal, herpetic, and streptococcal pathogens to the fetus during vaginal delivery. Obtain cervical cultures if indicated and manage appropriately, including the possibility of a Caesarian delivery.
To confirm the presence of a sexually transmitted disease in the neonate, examine and treat the mother and her sexual partner(s). If necessary, therapy can be modified when the results of culture and sensitivity are known.
The treatment prior to laboratory results should include topical erythromycin ointment and an IV or IM third-generation cephalosporin. Prompt treatment of gonococcal conjunctivitis is important, since this organism can penetrate an intact corneal epithelium and rapidly cause corneal ulceration. Because of the rapid progression of gonococcal conjunctivitis, patients with acute neonatal conjunctivitis should be treated for gonococcal conjunctivitis until culture results are available; the treatment is altered according to the laboratory results.
In cases of chlamydial conjunctivitis, systemic treatment is necessary because of the significant risk for life-threatening pneumonia.
Infants with a potentially sexually transmitted disease, such as gonorrhea or chlamydia, should undergo evaluation for other sexually transmitted diseases, such as syphilis and HIV,[13] as should the mother and her sexual partner(s).
Newborns with conjunctivitis are at risk for secondary infections, such as pneumonia, meningitis, and septicemia, which can lead to sepsis and death and thus should be admitted for full workup and treatment.
Bacterial conjunctivitis rarely fails to respond to treatment.
A consultation can be made with a pediatrician or pediatric infectious specialist in neonatal conjunctivitis, and the patient should be seen daily until response to treatment is confirmed.
Discharged patients should continue the treatment, according to clinical presentations and available culture results. Treatment may be modified later per culture results.
Avoid eye patching.
Treatment of neonatal chemical conjunctivitis is not necessary. Lubrication with artificial tear preparations may ease mild discomfort.
This infection is treated with oral erythromycin (50 mg/kg/d divided qid) for 14 days.
Topical treatment alone is ineffective. Topical erythromycin ointment may be beneficial as an adjunctive therapy.
Since the efficacy of systemic erythromycin therapy is approximately 80%, a second course sometimes is required.
Systemic treatment is important in cases of chlamydial conjunctivitis since topical therapy is ineffective in eradicating the bacteria in the nasopharynx of the infant, which could cause a life-threatening pneumonia if left untreated.
Neonates with a suspected herpes simplex infection should be treated with systemic acyclovir to reduce the risk of a systemic infection.
An effective dose is 60 mg/kg/day IV divided tid.
The recommended minimal duration is 14 days, but a course as long as 21 days may be required.
Infants with neonatal HSV keratitis should also receive a topical ophthalmic drug, most commonly 1% trifluridine drops or 3% vidarabine ointment. Topical ganciclovir 0.15% gel is now also available, although none of these topical agents is specifically approved for neonatal use.[15]
Topical antibiotics can also be considered to prevent secondary bacterial infections in cases with significant epithelial defects.
According to the 2012 Red Book, topical 0.5% erythromycin and 1% tetracycline are considered equally effective for prophylaxis of ocular gonorrhea infection in newborn infants. Each is available in single-dose tubes. Topical silver nitrate, povidone-iodine, and erythromycin are all effective in the prevention of nongonococcal nonchlamydial neonatal conjunctivitis. There is no agent that is currently effective in preventing the transmission of C trachomatis from mother to baby.[14] This is a change from the 2009 Red Book which stated that erythromycin or silver nitrate could prevent vertical transmission.[8]
Povidone-iodine solution (2.5%) is effective in preventing neonatal ophthalmia. Povidone-iodine is widely used outside of the United States. It is approved by the US Food and Drug Administration (FDA), but it is not commercially available in this country.[14]
Silver nitrate is the best agent in areas where the incidence of penicillinase-producing N gonorrhoeae (PPNG) is significant.[10]
The recommendations in the 2012 Redbook are for 2 drops of 1% silver nitrate or a 1 cm ribbon of antibiotic ointment (either erythromycin or tetracycline) placed into the lower conjunctival sac; both acceptable regimens for the prophylaxis of neonatal conjunctivitis.[4] Erythromycin ointment is considered the best regimen for prophylaxis against neonatal conjunctivitis because of its efficacy against gonococcal and nongonococcal nonchlamydial pathogens and owing to its low incidence of causing a chemical conjunctivitis.[10]
The goals of pharmacotherapy are to reduce ocular and systemic morbidity and potential mortality and to eliminate the infection.
Clinical Context: Systemic treatment is necessary. Erythromycin treats C trachomatis infection. Erythromycin inhibits ribonucleic acid (RNA) ̶ dependent protein synthesis, possibly by stimulating dissociation of peptidyl transfer RNA (tRNA) from ribosomes. This inhibits bacterial growth.
Topical antimicrobial therapy is not necessary (but may help) if systemic therapy is given.
Clinical Context: This is a bacteriostatic derivative of polycyclic naphthalene carboxamide; it is an alternative for chlamydial infection.
Clinical Context: Penicillin G is the choice for penicillin-susceptible N gonorrhoeae infection. It interferes with the synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.
Clinical Context: Bacitracin ophthalmic ointment for gram-positive cocci prevents the transfer of mucopeptides into the growing cell wall, inhibiting bacterial growth.
Clinical Context: Ceftriaxone is a treatment for penicillinase-producing N gonorrhoeae. It is a third-generation cephalosporin with broad-spectrum, gram-negative activity. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Ceftriaxone arrests bacterial growth by binding to 1 or more penicillin-binding proteins.
Clinical Context: An alternative treatment for N gonorrhoeae, cefotaxime arrests bacterial cell wall synthesis, which in turn inhibits bacterial growth.
Cefotaxime is a third-generation cephalosporin with a gram-negative spectrum. It has lower efficacy against gram-positive organisms.
Clinical Context: Systemic gentamicin is another alternative for penicillinase-producing N gonorrhoeae. Topical gentamicin also is used for other gram-negative bacterial infections.
Clinical Context: Tobramycin ophthalmic for gram-negative bacilli interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits, which results in a defective bacterial cell membrane. It is available as a solution, ointment, or lotion.
Clinical Context: Silver nitrate has been used to prevent gonorrheal ophthalmia neonatorum.
Clinical Context: Povidone-iodine is an antibacterial agent with broad antibacterial and antiviral activity. No bacteria are known to be resistant. Povidone-iodine is far less expensive and less toxic than agents currently used to prevent neonatal conjunctivitis.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Clinical Context: Acyclovir inhibits the activity of HSV-1 and HSV-2. Patients experience less pain and faster resolution of cutaneous lesions when this agent is used within 48 hours after rash onset. It may prevent recurrent outbreaks.
Clinical Context: A purine nucleoside, this is the drug of choice for herpes simplex keratitis. It is superior to either vidarabine or idoxuridine, having better penetration and greater effectiveness. It inhibits viral replication by incorporating into the viral DNA in place of thymidine. The topical preparation contains thimerosal preservative, known to be toxic to ocular epithelium. If trifluridine brings about no response in 7-14 days, consider other treatments.
Clinical Context: Ganciclovir is available in a 0.15% gel. It inhibits the activity of HSV-1 and HSV-2 and demonstrates similar herpetic clinical cure rates to topical acyclovir in adults. Ganciclovir targets viral infected cells only, thereby reducing surface toxicity.
Viral keratitis therapy begins with mechanical debridement of the involved corneal epithelium along with a rim of normal epithelium. This is followed by the topical instillation of antiviral medications such as trifluridine or acyclovir.