Atraumatic Red Eye

Context

The red eye is a common presenting complaint to the ED. Although accurate figures are not available for EDs, the acute red eye accounts for approximately 1-4% of all primary care consultations [1,2]. Its presence may indicate one of a wide range of acute eye problems, from relatively minor conjunctivitis to potentially eyesight-threatening acute angle closure glaucoma. The emergency physician must become familiar with all the different causes of a red eye and how to differentiate between them.

Definition

The red eye is a term used to describe the reaction of the eye to exogenous or endogenous inflammation or infection. It encompass inflammatory processes originating in the conjunctiva, episclera, sclera and anterior uveal tract. Non-traumatic subconjunctival haemorrhage is also commonly included in the causes of red eye [3] although it is usually not part of an inflammatory or infective process.

Basic Science and Pathophysiology

Three areas of basic eye anatomy and physiology are important to the understanding of the red eye; the composition of the uveal tract, the anatomy of the outer layers of the globe, and the mechanism by which aqueous humour is absorbed.

The uveal tract comprises the choroid (the layer between the sclera and retina), ciliary body and iris. The ciliary body provides support for the lens, enables the eye to accommodate and produces aqueous humour. Inflammation of the anterior segment of the uveal tract (the iris and ciliary body) is known as iritis or anterior uveitis.

The sclera, along with the cornea anteriorly, forms a tough protective shell for the eye. On the outer surface of the sclera are three distinct layers, from inner to outer, the episclera, Tenons capsule (fascia bulbi) and conjunctiva. The sclera is avascular and is supplied by the choroid inside the eye and also from a deep vascular plexus lying in the episclera. It is this plexus which becomes engorged, dilated and therefore easily visible, as part of the inflammatory process accompanying scleritis. The episclera also contains a superficial vascular plexus, which is distinct from the conjunctival vessel network, and which becomes inflamed in episcleritis.

Learning Bite

An understanding of the vascular supply of the different layers of the eye is important in differentiating clinically between episcleritis and scleritis.

Aqueous humour, produced by the ciliary body in the posterior chamber, flows into the anterior chamber through the narrow gap between the iris and lens. It is absorbed through the trabecular meshwork into a venous sinus known as the canal of Schlemm. Intraocular pressure is maintained by a constant cycle of production and absorption of aqueous humour. Obstruction of aqueous humour flow by closure of the gap between the lens and iris and/or blockage of the trabecular meshwork raises intraocular pressure and, in the acute situation, may precipitate acute angle closure glaucoma.

History

In taking a history from a patient with a red eye, the clinician must consider not only intrinsic eye problems as a cause, but also whether the red eye forms part of a systemic inflammatory disorder. The initial history must cover general features such as the duration and course of the problem and whether one or both eyes are affected. Other common non-specific symptoms described by patients with a red eye include;

• Watering
• Itching
• Discharge (clear or purulent) and stickiness, particularly on waking

Other symptoms may suggest a more serious cause for the red eye:

• Visual disturbance
• Pain particularly if severe
• Photophobia
• Current or previous joint or bowel symptoms

Specific questions may also point towards a particular diagnosis e.g.

Contact with others with similar symptoms	Infective conjunctivitis
Known inflammatory bowel or joint disease	Anterior uveitis or scleritis
Contact lens wear	Corneal infection or ulcer
Known atopic illness	Allergic conjunctivitis

Finally, in situations where it is clear there is a more serious cause for a red eye, it is important to take a thorough drug history. Many drugs can precipitate acute angle closure glaucoma in an already susceptible patient [4]. Some of the more common drugs include;

• Adrenergic agonists e.g. salbutamol
• Antidepressants particularly selective serotonin reuptake inhibitors e.g. fluoxetine, citalopram
• Anticholinergics hyoscine, atropine and ipratropium
• Antihistamines those with a mild anticholinergic effect e.g. chlorphenamine

Learning Bite

A number of commonly prescribed drugs may precipitate acute angle closure glaucoma as a result of either anticholinergic or adrenergic effects.

Examination

A comprehensive account of examination of the eye is included in the Initial assessment of the eye module.

The examination of any patient presenting with a red eye must begin with measurement of the visual acuity.

Examine the face for a dermatomal rash (seen in herpes zoster), other herpetic lesions and lymphadenopathy in the pre-auricular or submandibular regions. External examination of the eye will identify pathology related to the eyelids and tear duct.

Inspect the palpebral fissure in all directions of gaze to identify the nature and extent of redness;

• Generalised / peripheral conjunctival injection (prominence of blood vessels) typical of conjunctivitis
• Localised injection a feature of episcleritis
• Perilimbal injection suggests either a corneal, anterior chamber or anterior uveal problem
• Blood in the subconjunctival space identifies a subconjunctival haemorrhage

Learning Bite

The distribution of redness in the eye is a useful sign, in some cases pointing directly to the correct diagnosis.

Inspection may also reveal:

• Conjunctival oedema (chemosis)
• Opacification (clouding) of the cornea
• Pus in the anterior chamber (hypopyon)

The pupil must be examined for size, shape and reaction to light. A mid-size, unreactive pupil is a classic sign of acute angle closure glaucoma. An irregular or oval iris is a sign of anterior uveitis or previous ophthalmic surgery.

All patients should have fluorescein instilled into the eye to look for epithelial defects. Examination with a slit lamp will enable the clinician to identify small corneal lesions, and flare and inflammatory cells in the anterior chamber, typically found in anterior uveitis.

If facilities exist, the intraocular pressure should be measured if acute angle closure glaucoma is suspected.

Finally, a general examination of the patient may be required for signs of systemic features associated with some causes of the red eye e.g. inflammatory joint and bowel disorders

Investigations are usually unnecessary in the majority of patients presenting with a red eye

Exceptions include:

• Eye swabs where chlamydial infection is suspected
• Eye swabs where infective conjunctivitis is severe or fails to respond to treatment
• Measurement of rheumatological and inflammatory markers in scleritis and anterior uveitis.

Although the majority of patients presenting to the ED with red eye can be managed by the EP alone, significant doubt regarding the diagnosis or failure of the patient to respond to previous treatment should prompt a second opinion from either a senior clinician or an ophthalmologist.

Conjunctivitis

Conjunctivitis is the commonest cause of red eye and can be bacterial, viral or allergic.

Bacterial and Viral Conjunctivitis

Bacterial conjunctivitis accounts for approximately 50% of all adult cases of conjunctivitis where swabs were taken [5] and between 2/3 and 4/5 of cases in children [6,7]. Common causative organisms include strep. pneumoniae, staph. aureus and haemophilus influenzae. Gonococcal and chlamydial conjunctivitis are rarer but potentially far more serious and should be suspected in;

• Neonates
• Adults with urogenital symptoms i.e. urethral or vaginal discharge
• Patients who fail to respond to initial treatment.

If either gonococcal or chlamydial conjunctivitis suspected, an eye swab should be taken and the patient referred for an ophthalmology assessment.

Learning Bite

Always consider gonococcal and chlamydial conjunctivitis in neonates, sexually active adults and patients whose symptoms fail to respond to initial treatment.

Viral conjunctivitis is commonly caused by infection with adenovirus, but other viruses (e.g. mumps, measles and herpes) may also be responsible. The infection is easily transmitted from eye to eye and between family members.

Common but non-specific findings in both viral and bacterial conjunctivitis include generalised conjunctival injection more pronounced at the peripheries, watering, discharge and itching of the eye(s). A follicular reaction (tiny, avascular, white or grey patches of the tarsal conjunctiva) may also be found and are said to be a sign of viral conjunctivitis.

Many standard texts claim that distinguishing between viral and bacterial conjunctivitis clinically, is straightforward. However, a systematic literature search found no evidence to support any symptom or sign [8] being specific to one or the other. A more recent study [9] has suggested that three indicators may prove useful;

• Early morning eyelid stickiness makes bacterial conjunctivitis more likely
• Itching and a previous history of conjunctivitis both favour a viral aetiology

Learning Bite

Differentiating between viral and bacterial conjunctivitis, clinically, is unreliable and cannot be used to guide treatment.

Treatment of infective conjunctivitis with topical antibiotics is controversial. A Cochrane review found that although the signs of conjunctivitis went away more quickly in patients given antibiotic eye drops, the benefits were marginal as, in most cases, the infection is self-limiting. Almost 2/3 of patients treated with placebo recover within 5 days [9].

A recently suggested treatment pathway [10] has addressed this issue and balances the positive treatment aspects of reduced transmission of infection and time off work, with the potential harmful effects of increased risk of antibiotic resistance and side effects.

Always prescribe topical antibiotics:

• Purulent / mucopurulent secretion and patient discomfort and ocular redness
• Patients and staff in nursing homes, neonatal units, critical care units etc
• Children going to nursery
• Contact lens wearers
• Patients with dry eyes or corneal epithelial disease

Usually prescribe topical antibiotics:

• Purulent / mucopurulent secretion and severe ocular redness
• Patients with previously known external ocular disease

Delayed prescription or no antibiotic treatment:

• Patients who do not want immediate antibiotic treatment
• Patients with moderate mucopurulent discharge and little or no discomfort
• Co-operative and well informed patients

Learning Bite

Topical antibiotics provide a marginal benefit in infective conjunctivitis and should only be used where severe symptoms are present or specific high risk factors exist.

The two most common topical antibiotics prescribed are chloramphenicol and fusidic acid. Numerous studies have failed to show a significant difference between the clinical effect of these agents [10].

Allergic Conjunctivitis

Allergic conjunctivitis is typically a seasonal problem and commonly associated with other atopic diseases. Symptoms include itching and watering of the eyes, and findings on examination include bilateral generalised conjunctival injection, eyelid swelling and occasionally conjunctival oedema. The problem is managed by removing exposure to the pathogen, application of cool compresses to the eyes and in severe cases, an oral or topical ocular antihistamine.

Oedema of the conjunctiva in allergic conjunctivitis

Non-traumatic Subconjunctival Haemorrhage

This problem occurs when conjunctival or episcleral vessels bleed into the subconjunctival space. In spontaneous (non-traumatic) haemorrhage, the cause may be a valsalva manoeuvre (e.g. coughing) or trivial trauma. Other systemic causes must be excluded and the patients blood pressure and coagulation status (if taking anticoagulant medication) need to be checked.

Provided no other cause is found, the patient should be reassured and informed that the haemorrhage normally takes 2-3 weeks to resolve completely.

Keratitis and Keratoconjunctivitis

Inflammation of the cornea, either alone (keratitis) or in combination with conjunctivitis (keratoconjunctivitis), is distinguished by symptoms of pain, photophobia and reduction in visual acuity. Examination may show localised opacification of the cornea but more typically, fluorescein staining from corneal ulceration in a punctuate, rounded or branching (dendritic) pattern seen in herpes simplex keratitis.

Bacterial keratitis is rare and is more common in contact lens wearers where staphylococcus and pseudomonas aeruginosa are the most frequent causative organisms [11].

All patients with keratitis, keratoconjunctivitis or corneal ulcer must be reviewed by an ophthalmologist for further investigation, treatment and follow-up.

Acute Angle Closure Glaucoma (AACG)

AACG develops when drainage of aqueous humour through the trabecular meshwork is blocked by folds of the iris occurring on dilation of the pupil. The intraocular pressure (normally up to 21 mmHg) rises acutely causing pressure related symptoms and signs. AACG is more frequent in elderly hypermetropes (long sighted) due to a shallower anterior chamber and may be associated with recent changes in medication, particularly drugs with anticholinergic effects. Patients often describe prodromal symptoms of haloes or rainbows around bright lights, often in the evening when the pupil dilates, which ease on going to sleep.

In the acute presentation however, systemic symptoms such as nausea, vomiting, headache and abdominal pain may predominate, confusing the unwary clinician [12] . On examination the eye is painful with reduced visual acuity, perilimbal conjunctival injection and a hazy cornea. The pupil is mid-dilated and unreactive to light.

Learning Bite

Acute angle closure glaucoma may cause significant systemic symptoms but a painful red eye with reduced acuity and a fixed and mid-dilated pupil, are cardinal signs and need an emergency ophthalmic opinion.

If AACG is suspected, the patient must be referred for an urgent ophthalmology assessment. Treatment should be commenced e.g. opiate analgesia for pain, anti-emetic (if required) for nausea and IV acetylzolamide 500mg IV to reduce the intraocular pressure. Treatment with a topical miotic such as pilocarpine 1 or 2% every 5 minutes should be started approximately 1 hour after commencing other measures as initially the pupil is usually paralysed and unresponsive.

Episcleritis

Localised, engorgement of the superficial episcleral plexus is the hallmark of this condition which may occur in isolation or together with uveitis or keratitis. Although normally benign, episcleritis may be associated with rheumatological and inflammatory diseases such as rheumatoid arthritis, sarcoidosis and inflammatory bowel disease. Patients describe irritation, rather than pain, in the eye with a mild watery discharge and no disturbance of vision [13].

Patients should be reassured and advised that the condition is self-limiting. A topical non-steroidal anti-inflammatory agent may ease discomfort.

Scleritis

Scleritis is an inflammatory process involving the deep episcleral plexus and in 30-50% of cases [3] is associated with an underlying rheumatological disorder. Rheumatoid arthritis and Wegeners granulomatosis are the most common connective tissue and vasculitic causes. Patients present with either localised or generalised bluish or violet discolouration and a deep dull aching pain in the eye. The pain is characteristically worse at night and may wake the patient from sleep. Vision may be affected and, as the extra-ocular muscles attach to sclera, the pain is worse on movements of the eye. The eye is tender to touch through the closed eyelid [14].

Differentiation between episcleritis and scleritis may be difficult. However, instillation of 2.5% phenylephrine drops into the affected eye results in blanching of the superficial episcleral plexus after 5 minutes. Therefore, persisting vascular engorgement indicates scleritis.

All patients with suspected scleritis must be referred for an urgent ophthalmological assessment as, in severe cases, the inflammation may lead to thinning and ultimately, perforation of the globe.

Learning Bite

Blanching of the superficial episcleral plexus by phenylephrine is a useful indicator of episcleritis.

Anterior Uveitis (Iritis)

Anterior uveitis may be a primary or secondary disorder. It is strongly associated in 70% of cases with the HLA-B27 serotype [15]. Although sometimes occurring in eye disorders such as herpetic keratitis and following recent intraocular surgery, it is more commonly associated with diseases such as sarcoidosis, ankylosing spondylitis and inflammatory bowel disease.

A typical presentation is of a painful, photophobic eye; the pain is described as deep, boring and worse on accommodation (due to constriction of the iris). Photophobia may be consensual i.e. the patient experiences discomfort when light is shone into the unaffected eye. There is perilimbal injection on examination and although the pupil may appear normal [16] it may be irregular due to the formation of adhesions (synechiae) between the iris and lens. On slit lamp examination, inflammatory cells and flare may be seen.

Learning Bite

A painful eye with perilimbal injection, photophobia and an irregular pupil are all indicative of anterior uveitis. The presence of keratitic precipitates, inflammatory cells and flare confirm the diagnosis.

All patients with suspected anterior uveitis must be referred for an urgent ophthalmology assessment.

• The red eye is the presenting symptom of a number of disease processes, from relatively minor self limiting problems to potentially sight-threatening disorders. (level of evidence 5)
• Clinical assessment must include both evaluation of the eye and consideration of the many systemic conditions which may present with a red eye. (level of evidence 5)
• The presence of altered vision, eye pain and photophobia all suggest a more serious cause for the red eye. (level of evidence 5)
• It is not possible to reliably differentiate between viral and bacterial conjunctivitis clinically. (level of evidence 5)
• Topical antibiotics offer a marginal benefit in infective conjunctivitis as almost 2/3 of patients will recover without treatment within 5 days. (level of evidence 2a)
• Acute angle closure glaucoma may present with a predominance of extraocular symptoms which may result in the diagnosis being missed. (level of evidence 5)
• It is vital to differentiate between episcleritis and scleritis which may present to the ED in similar ways but which have very different clinical outcomes. (level of evidence 5)
• Inflammatory cells, flare and keratitic precipitates in the anterior chamber are diagnostic features of anterior uveitis and are best seen on slit lamp examination of the eye. (level of evidence 5)

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