Ophthalmia neonatorum

Synonym: conjunctivitis of the newborn, neonatal conjunctivitis

Definition and aetiology^{1 2}

Ophthalmia neonatorum (ON) refers to any conjunctivitis occurring in the first 28 days of life. Originally, the term neonatal ophthalmia referred to conjunctivitis in the newborn caused by Neisseria gonorrhoeae, but now the term is used for any conjunctivitis in this age group, irrespective of cause.

It is most commonly infective in origin. N. gonorrhoeae was the most common cause of infective ON in the past, but now accounts for less than 1% of reported cases in the UK. Chlamydia trachomatis took over as the most common single cause of infective neonatal conjunctivitis. However, incidence of both these pathogens has declined over recent decades, due both to decreased prevalence in the population and to the introduction of prenatal screening, although they are much more common in less developed countries. Non-sexually transmitted bacteria, such as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas and Haemophilus species and other Gram-negative bacteria, make up most of the remaining ophthalmia neonatorum cases (30-50%). Viral infections are less common and can be caused by herpes simplex virus, adenovirus or enterovirus.

It may also occur as a reaction to chemical irritants, in particular silver nitrate, which has been used for prophylaxis in the past in the UK, and still is in many other countries.

In most cases ophthalmia neonatorum is a mild illness. Untreated infection, however, particularly gonococcal infection, can progress rapidly to corneal damage and permanent visual impairment. As of April 2010, ophthalmia neonatorum is no longer a notifiable disease in the UK³ .

Epidemiology²

Prevalence varies significantly in different parts of the world, depending on socio-economic status, standards of maternal healthcare and prevalence of sexually transmitted infections. An analysis in England of hospital episode statistics from 2000 to 2011 in England found the incidence rate of hospitalised cases of ophthalmia neonatorum to be 257 per 100,000 live births in 2011⁴ . In 2003, incidence of chlamydia-induced ON was 6.9 per 100,000 live births, and of ON caused by gonorrhoea, 3.7 per 100,000 live births. Incidence of chemical conjunctivitis is higher in countries that use prophylaxis, but decreasing as silver nitrate prophylaxis is being replaced by other agents (see 'Prevention', below) which in turn, have significantly reduced the incidence of gonococcal conjunctivitis.

In the past, ophthalmia neonatorum has been one of the most common causes of visual loss, reportedly accounting for 45% of blindness in Paris, and up to 80% in blind institutions in Germany in the late 1800s⁵ . These types of figures have reduced worldwide, but the condition remains an important cause of loss of sight in developing countries.

The main risk factor for ophthalmia neonatorum of gonococcal or chlamydial origin is the presence of a sexually transmitted disease in the mother. There is a high rate of transmission (30-50%) from infected mother to infant.

Presentation

Affected babies present with a purulent, mucopurulent or mucoid discharge from one or both eyes within the first month of life. They typically show injected conjunctiva and lid swelling. There may be associated systemic infection.

Chemical conjunctivitis

There is a mild irritation, tearing and redness in a baby who has been administered prophylactic silver nitrate (used for the prevention of gonorrhoeal infection) within the preceding 24-48 hours.

Bacterial conjunctivitis

This usually (but not invariably) has a longer incubation period than for the other infective causes, presenting with a subacute onset between the 4th and 28th day of life. Depending on the pathogen, there may be a mixed picture of a red eye with lid swelling and a varying amount of purulent discharge. Specific common types of bacterial infection are:

• Gonorrhoeal infection - typically, 2-5 days after birth but it may occur later: hyperacute conjunctival injection and chemosis, lid oedema and severe purulent discharge. There may be associated corneal ulceration and perforation.

• Chlamydial infection - 5-12 days after birth (some report up to 28 days after birth): unilateral/bilateral watery discharge which becomes copious and purulent later on. There may be associated preseptal cellulitis and, less commonly, rhinitis, otitis and pneumonitis. The eyes are usually less inflamed than in the case of gonococcal infection.
  

Viral conjunctivitis

Onset is acute, 1-14 days after birth: unilateral/bilateral serosanguinous discharge ± vesicular skin lesions. Other ocular features may include keratitis, anterior uveitis, cataract, retinitis and (rarely) optic neuritis. Uncommonly, systemic infection can cause jaundice, hepatosplenomegaly, pneumonitis, meningoencephalitis and disseminated intravascular coagulation.

Differential diagnosis

A blocked nasolacrimal duct is common and results in a thick (sometimes copious) discharge which may be sticky or crusty. The eye is not red and the baby is otherwise well. The discharge may be intermittent and responds well to simple cleansing. Most babies' ducts clear as they grow, the majority functioning normally by 12 months of age.

In the UK a blocked nasolacrimal duct is more likely to be the cause of sticky eyes in newborns presenting to GPs. This does not usually result in the conjunctiva being red or the eyelids being swollen. Refer all newborns with red and sticky eyes .

Investigations^{6 7}

For the GP: as above, a neonate with red and sticky eyes or with very profuse discharge or swollen eyelids/surrounding cellulitis should be referred immediately for specialist assessment. In the absence of red flags, a baby under a month old with sticky eyes not being referred should have swabs taken of the pustular material for bacterial culture and for chlamydia. Some laboratories can do a combined molecular test for gonorrhoea and chlamydia (nucleic acid amplification test ( NAAT)). The purpose of the test must be explained to the parent(s) as there may be implications for the parents should it prove positive.

For a specialist eye unit: other aspects of investigation in a specialist eye unit under consultant direction include:

• History - previous or concurrent sexually transmitted disease in the mother and results of any cervical cultures obtained during pregnancy.

• Ocular examination - pen light and fluorescein examination.

• Microbiological investigations - conjunctival swabs (ideally obtained from the everted lid) and cultures including for chlamydial detection and viral cultures. The Gram staining is requested urgently where there is suspicion of gonococcal conjunctivitis. Even if gonorrhoeal infection is strongly suspected, investigation for chlamydia should be carried out and vice versa in the case of suspected chlamydial infection.

• Maternal investigations - the mother will need cervical swabs for gonorrhoea, chlamydia and viral infection and so will need to be seen at the genitourinary medicine clinic. There must also be efforts to trace sexual partners.

Management^{8 9}

Referral

The majority of neonates presenting with a sticky discharge have a benign cause - most frequently due to blocked nasolacrimal duct(s). Features suggesting that referral is necessary are those suggestive of possible gonococcal involvement, and include:

• Conjunctival redness, especially if the bulbar conjunctiva (overlying the sclera) is involved.

• If the onset is sudden and severe.

• If the baby is distressed or unwell.

• If both eyes are affected.

• If maternal gonococcal infection is suspected.

• If the mother is concerned, or you are concerned.

If you suspect gonococcal infection, refer immediately. Early and appropriate treatment have long been recognised as the key to preventing consequent severe sight impairment.

Treatment of ophthalmia neonatorum is managed by a specialist.

Initial therapy

Depending on the assessed risk (from signs, history, local prevalence), prior to results from Gram staining (or if these are inconclusive), it may be appropriate to start the infant on a broad-spectrum antibiotic or treatment for both chlamydia and gonorrhoea until the microbiological results have come back. If the initial infection recurs, chlamydia should be reconsidered (even if the baby first tested negative), as this organism is difficult to demonstrate in the laboratory and can be missed.

Chemical conjunctivitis

This is a self-limiting condition. No treatment is required, although some favour the use of preservative-free artificial tears qds. These babies need early review (24 hours) to confirm that this was indeed a case of chemical irritation as opposed to early infection.

Bacterial infection

Treatment should be guided by the organism grown. If there is corneal involvement, the baby may be hospitalised and treated as for microbial keratitis.

Chlamydial infection
The recommended treatment is erythromycin 50 mg/kg/day orally divided into 4 doses daily for 14 days. The alternative is azithromycin 20 mg/kg/day orally, 1 dose daily for 3 days. In either regime, monitor for signs of infantile hypertrophic pyloric stenosis, which is reportedly more common in infants given either of these agents under the age of 6 weeks. Follow-up and a second course may be needed, as efficacy is about 80%. Topical treatment alone is not sufficient (and is not felt to be necessary when systemic treatment is taken). The presence of chlamydia in the eyes invariably indicates its presence in the respiratory tract too, which is a further reason for systemic therapy. The mother and her sexual partner(s) will also need treating.

Gonorrhoeal infection
These babies need hospitalisation and evaluation for disseminated disease. Hourly saline lavage is recommended to remove the discharge (qds). The recommended treatment is ceftriaxone 25-50 mg/kg IV or IM in a single dose, not to exceed 125 mg. The mother and partner should be treated for sexually transmitted infection.

Other bacterial infections
Many can be treated with topical antibiotics. Pseudomonas infections require both topical and systemic treatment, and isolation.

Viral infection

These babies should be hospitalised and treated with IV aciclovir (full-term infants: 45-60 mg/kg/day in divided doses. This is continued for 14 days if there is limited disease and 21 days if there is disseminated disease, which can be devastating) in addition to topical antiviral preparations.

Complications

The complications mainly relate to gonococcal conjunctivitis. Most other causes of conjunctivitis in the newborn are fairly benign. Gonococcal complications include:

• Keratitis.

• Conjunctival scarring.

• Superior corneal pannus.

• Side-effects of treatment (rarely), such as the association between oral macrolides and infantile hypertrophic pyloric stenosis (IHPS) reported in infants aged <6 weeks.

• Permanent visual impairment.

Other bacteria can (rarely) have serious consequences:

• Overwhelming systemic infection may occur - eg, chlamydial pneumonia, disseminated herpes simplex.

• Pseudomonas spp. infection is very rare but may be devastating, causing keratitis; in disseminated cases, it can ultimately lead to death.

Prognosis

• Chlamydial infection: - 80% fully recover after one course of treatment. Further treatment courses may be required .

• Bacterial infection: rarely fails to respond to treatment when this is prompt and appropriate, but missed infections can result in severe sight impairment or even death.

• Viral infection: the ocular prognosis can be poor and the systemic sequelae may be fatal.

• Chemical irritation: good - full spontaneous recovery expected after 24-36 hours.

Prevention

Prenatal maternal screening and treatment for sexually transmitted infections is the best method of prevention of this condition .

In some countries, prophylactic treatment for neonates is still routine, although this was abandoned in the UK in the 1950s. Traditionally, this has involved the use of 2% silver nitrate ophthalmic solution. More recently topical erythromycin has been used more commonly, as it is less likely to cause transient chemical conjunctivitis and is considered slightly more effective¹⁰ . Tetracycline drops are also used⁹ . Prophylaxis is required by law in many parts of the USA and Canada ¹¹ . Topical prophylaxis is not effective in preventing ON due to chlamydial infection.

Dr Mary Lowth is an author or the original author of this leaflet.