Yusuf Mushtaq
Luton and Dunstable University Hospital, Bedfordshire Hospitals NHS Foundation Trust, Luton, UK

Maryam Mushtaq
School of Clinical Medicine, University of Cambridge, Cambridge, UK

Aims

This article aims to help the reader understand the serious and potentially sight-threating causes of red eye. With an increased demand on hospital eye services, more patients with eye symptoms are being seen in primary care settings. Therefore, it is extremely important for primary care physicians to know when to refer urgently for specialist assessment.

Introduction

General Practitioners (GPs) are usually the first port of call for patients who are worried about a red eye. This is understandable, as most causes of red eye are usually benign and can be treated in primary care.  However, Ophthalmology is generally perceived by GPs as a difficult area in which they lack confidence [1]. Despite up to five percent of primary care consultations being eye related, 96% of General Practitioners in the United Kingdom do not undergo postgraduate Ophthalmology training [2] and most view their undergraduate ophthalmic education as inadequate [3].

Nonetheless, there is a wide differential diagnosis of red eye and common causes are often effectively managed by GPs alone. However, knowing when to refer a patient for urgent assessment by an Ophthalmologist is vital in preventing serious complications.

Differential Diagnoses

The differential diagnoses for red eye can be categorised into 5 main anatomical categories. These are outlined in the table below:

ADNEXAL	CONJUNCTIVAL	CORNEAL	INFLAMMATORY	OTHER
Dry eye	Bacterial conjunctivitis	Bacterial ulcer*	Anterior uveitis*	Angle closure glaucoma*
Blepharitis	Viral conjunctivitis	Viral ulcer*	Scleritis*	Chemical trauma*
Trichiasis	Allergic conjunctivitis	Fungal ulcer*	Episcleritis	Penetrating ocular trauma*
Entropion	Neonatal conjunctivitis*	Parasitic ulcer*		Migraine
Ectropion	Subconjunctival haemorrhage	Contact lens*
	Subtarsal foreign body	Corneal foreign body
	Conjunctival foreign body	Corneal abrasion

Table 1 – Differential diagnoses of red eye classified based on anatomical location.

*Would warrant urgent referral for discussion or same-day assessment by an Ophthalmologist. These will be discussed in more detail below. All those in bold are potentially serious.

The most common conditions causing red eye that present to a primary care physician are adnexal problems, infective conjunctivitis, allergic conjunctivitis and subconjunctival haemorrhage. If a foreign body cannot be removed or a patient cannot tolerate assessment, then immediate referral is also needed. A thorough patient history and eye examination is key to ensure that nothing serious is missed.

The Three Clinical Questions

Ophthalmology GPSI, Dr. Anup Shah, highlights three questions that must not be missed from the history of presenting complaint [4]:

1. Is there any eye pain?
2. Is there any blurring?
3. Is there sensitivity to light (photophobia)?

If the answer to any of the above is yes, the cause is likely to be serious. If no to all three, then it is unlikely to be not. The following section will discuss the potentially sight-threatening causes of red eye and why the above questions are so vital to ask.

Corneal

A corneal ulcer (also known as keratitis) is an open sore on the cornea and can be classified based on aetiology (infective or non-infective), location (central, paracentral or peripheral) and depth (deep or superficial). Corneal ulcers as a result of infection are more commonly seen in primary care. These are usually due to bacterial, viral, fungal or parasitic (acanthamoeba) infections. Foreign bodies can also 

Bacterial Keratitis

Bacterial causes are the most common and occur more frequently in contact lens wearers. A common pathogen is Pseudomonas Aeruginosa and is responsible for over 60% of contact lens-related keratitis [5]. Other common pathogens are Staphylococcus aureus, Streptococcus Pyogenes and Streptococcus Pneumoniae. These often present as well-defined, white infiltrates on the cornea.

A patient may initially report a foreign body sensation, progressing to blurred vision, photophobia, severe pain and discharge with swelling of the eyelids. Patients often score highly on a 0-10 pain scale and if left untreated, symptoms will worsen. If the patient presents with mild discomfort that worsens as the day progresses or during certain tasks, such as screen time and reading, then the diagnosis is more likely to be adnexal conditions such as blepharitis or dry eye.

Patients with a suspected corneal ulcer must be seen urgently by a specialist on the same day. They will examine the eye with a slit lamp and often perform a corneal scrape for microscopy, culture and sensitivity. Conjunctival swabs may also be worthwhile and sometimes contact lens cases can be sent to laboratories too.

Culture and sensitivity reports should be obtained as quickly as possible, but topical, broad-spectrum antibiotic treatment is usually initiated before microscopy results are available. Steroids can reduce host inflammation and minimise corneal scarring, but can promote the replication of Herpes Simplex Virus, Mycobacteria and fungal infections. Systemic antibiotics are not usually given unless there is severe corneal thinning with threatened perforation or in Neisseria Meningitidis, Neisseria Gonorrhea or Haemophilus Influenza infection.

Viral Keratitis

A common cause of viral keratitis is Herpes Simplex Virus 1 (HSV1). Approximately 10 million people worldwide may have herpetic eye disease and as many as 60% of corneal ulcers in developing countries may be the result of HSV [5]. Presenting symptoms are similar to bacterial keratitis and an urgent referral to a specialist is needed. A corneal scraping can be sent for polymerase chain reaction (PCR) but the ophthalmologist would usually make the diagnosis based on the clinical signs alone. Stellate lesions and a classic dendritic ulcer can be seen when the eye is stained with fluorescein. Margins of the dendritic ulcer stain well with rose Bengal. Treatment is with topical aciclovir and ganciclovir.

Fungal Keratitis

Fungal keratitis is a major cause of visual loss in developing countries and rarer in developed areas of the world. Common predisposing factors include systemic immunosuppression, the long-term use of topical steroids and diabetes. The symptoms are similar to the other infective causes mentioned above, but a yellow-white dense infiltrate is typical in Candidal keratitis [5]. Potassium hydroxide staining with direct microscopic evaluation can be a highly sensitive rapid diagnostic tool but samples for laboratory investigation should be acquired before commencing antifungal therapy.  

Acanthamoeba Keratitis

Acanthamoeba is an organism that is found in bodies of water (lakes and rivers) as well as swimming pools, domestic tap water, soil and air [6]. In the early stages, Acanthamoeba keratitis has similar signs and symptoms to other microbial corneal infections but the primary difference is that it is challenging to treat. Therefore, it is important to maintain a high index of suspicion in any patient with limited response to antibacterial treatment [5].

Characteristic signs include perineural infiltrates (radial keratoneuritis) in the first few weeks and a ring abscess that can form in advanced disease. A corneal scrape, culture and PCR can also be done to confirm diagnosis. Treatment is usually with antiseptic drops, such as polyhexamethylene biguanide (PHMB), chlorhexidine, hexamidine or propamidine (Brolene) [5, 6].

Simple preventative measures that primary care physicians can instil in their patients for all the above include not wearing contact lenses overnight or for extended periods of time, to not shower whist wearing contact lenses and for good hand, lens and storage case hygiene.

Conjunctival

Neonatal Conjunctivitis

Neonatal conjunctivitis or Ophthalmia neonatorum (ON) occurs within the first four weeks of life. It has a distinct diagnosis from conjunctivitis in adults because it is potentially very serious with potential ocular and systemic complications. It is often the result of infection transmitted from the mother to the infant during delivery.  Chlamydia Trachomatis is the most common cause in moderate to severe conjunctival inflammation. Babies born to women with untreated chlamydial infection at delivery have a 30-50% chance of developing ON. Staphylococci are responsible in mild conjunctivitis cases. Other infective causes include Gonococcal and HSV. Non-infectious causes include congenital nasolacrimal obstruction and previously the use of prophylactic silver nitrate eye drops, which have been abandoned in the UK in the 1950s, causing chemical conjunctivitis [7].

Unfortunately, this is an example where the child cannot tell us an answer to any of the ‘three crucial questions’ and symptoms are usually described by the mother. Commonly, there is bilateral redness, with discharge and swelling of the eyelids. Another important component of the history included timing of onset [5]:

• Chemical irritation: first few days
• Gonococcal: first week
• Staphylococci and other bacteria: end of the first week.
• HSV: 1–2 weeks.
• Chlamydia: 1–3 weeks.

Any suspected case of neonatal conjunctivitis seen in primary care should be referred urgently to a specialist.

Investigations include obtaining any parental prenatal testing for sexually transmitted infections, conjunctival scrapings for PCR and conjunctival swabs. Treatment depends on the severity of the conjunctivitis. Chlamydial infection is often treated with 2 weeks of oral erythromycin. Paediatric specialist involvement is mandatory if systemic disease is present. HSV is always regarded as a systemic condition and is treated with high-dose intravenous aciclovir. Neisseria Gonorrhea infection is treated with systemic penicillin G or cephalosporin, with topical erythromycin and cover for chlamydia infection too.

Inflammatory

Uveitis

Uveitis is inflammation of the middle layer of tissue in the eye wall (called the uveal tract) and includes the iris, ciliary body and choroid [8]. Inflammation of nearby tissues such as the retina, the optic nerve and vitreous humour may occur. Classification of uveitis is based on the anatomical structures involved [9]:

• Anterior uveitis is the most common and affects the anterior segment of the eye.
• Intermediate uveitis is inflammation of the vitreous.
• Posterior uveitis is inflammation of the retina or choroid.
• Panuveitis is inflammation of all uveal structures.

Acute anterior uveitis (AAU) is the most common presentation, with idiopathic or HLA-B27 related forms making up the largest proportion. AAU can also be due to infection and systemic autoimmune disorders such as Sarcoidosis, Juvenile Idiopathic Arthritis and Systemic Lupus Erythematosus.

Clinical features often include rapid onset unilateral painful, red eye with blurred vision, watering of the eye, photophobia, flashers or floaters. If there is severe pain and reduction in vision, then the person should be referred immediately for same day assessment by an ophthalmologist.

Signs of uveitis are broad, and most can be viewed through a slit lamp. These can include ciliary injection, anterior chamber cells (an indicator of inflammatory activity), miosis and a hypopyon to name a few. Investigation is often negative, with no clear underlying cause in many patients. Investigation is not usually indicated in a single episode of unilateral, moderate AAU with no ocular or systemic suggestion of underlying disease. If symptoms are severe and recurrent, a wide range of investigations can be done, including blood tests, ocular imaging and biopsies, but are tailored to each patient depending on clinical signs.

Treatment should not be commenced in primary care unless instructed by an ophthalmologist. For non-infectious uveitis, topical steroids such as prednisolone 1% or dexamethasone 0.1% are used. Cycloplegic agents can promote comfort by relieving spasm of the pupillary and ciliary muscle. For infectious causes, the appropriate topical preparations are used.

Scleritis

Scleritis is a rare condition, much less common than episcleritis and is usually non-infectious. Immune-mediated scleritis is the most common type and is frequently associated with an underlying systemic inflammatory condition. Thus, it is extremely important for clinicians to note past medical history and specifically note any systemic associations and connective tissue disorders. Scleritis can be associated with rheumatoid arthritis, granulomatosis with polyangiitis, polyarteritis nodosa, systemic lupus erythematosus, inflammatory bowel disease, sarcoidosis, tuberculosis and syphilis.

Clinical features can include gradual onset, severe, unilateral ocular pain. In anterior scleritis (90% of cases), there is obvious, prominent redness throughout the sclera. Whereas in posterior scleritis (10% of cases), the redness will be posterior the ora serrata. There is often no discharge and reduced visual acuity may be present. The person must be referred immediately for assessment by an ophthalmologist.

Treatment includes topical steroids to relieve oedema and systemic non-steroidal anti-inflammatory drugs (NSAIDs) if there are no contraindications. Systemic steroids are used when NSAIDs are inappropriate or inadequate such as in necrotising disease. It is important to involve the appropriate specialist such as a rheumatologist or acute physician when managing these patients.

Other

Angle-Closure Glaucoma

Glaucoma can be classified broadly in many ways: congenital or acquired, open angle or angle closure and primary or secondary. All forms of the disease have in common a characteristic potentially progressive optic neuropathy, associated with visual field loss as a result of increased intraocular pressure (IOP). Open angle or angle closure types are distinguished based on the mechanism by which aqueous outflow is impaired with respect to the anterior chamber angle configurations. Distinction can be made between primary and secondary, with the latter meaning that a recognisable ocular or non-ocular disorder contributes to the elevated IOP.

Angle closure glaucoma occurs due to occlusion of the trabecular meshwork by the peripheral iris obstructing aqueous outflow. Angle closure can be primary (PACG), when it occurs in an anatomically predisposed eye, or secondary to another ocular or systemic factor. PACG may be responsible for up to half of all cases of glaucoma globally, with a particularly high prevalence in individuals of Far Eastern descent [10]. It is typically associated with greater rapidity of progression and visual morbidity than POAG. Precipitating factors can include looking at a bright screen in a dark room, reading in a semi prone position or adrenergic and antimuscarinic medications [11].

Typical symptoms include a unilateral, painful red eye associated with headache and nausea. Impaired visual acuity is common with blurring and rainbow haloes that form around lights, due to corneal epithelial oedema. A classical sign is a semi-dilated, fixed pupil in a vertically oval shape. It is important to note that chronic angle closure is usually asymptomatic and subacute angle closure causes less severe symptoms that soon resolve.

If a diagnosis of any angle-closure is suspected, immediate referral for specialist ophthalmology assessment is required. An ophthalmologist can confirm the diagnosis, measuring the intraocular pressure as well as using gonioscopy to see any iridotrabecular contact.  If this immediate admission is not possible then treatment can be commenced in primary care to reduce the production of aqueous humour. This includes pilocarpine eye drops and acetazolamide provided there are no contraindications. It is helpful to lie the patient completely flat, with no pillows, to relieve some pressure on the angle.

Specialist treatment include laser iridotomy to alleviate any pressure difference between the anterior and posterior chambers in the eye. If this does not completely resolve the symptoms, then laser iridoplasty is done with long term pilocarpine prophylaxis.

Blunt and penetrating trauma

Trauma to the globe can cause contusion, rupture, laceration and perforation of several tissue structures in the eye.

It is particularly important to identify the nature, force and time of the injury, particularly with high-velocity small fragments. Most traumatic eye injuries will need urgent assessment by a specialist, with high impact or fragment injuries very concerning.

Patients may present with reduced visual acuity, red eye due to conjunctival injection or subconjunctival haemorrhage, an irregular pupil and associated lid and facial injuries. Closer inspection by an ophthalmologist can reveal hyphaema (blood in the anterior chamber), corneal abrasion, laceration, oedema, lens damage and possible uveal tissue prolapse.

Investigation can include plain radiographs and ultrasonography if a foreign body is suspected, but computed tomography (CT) provides a more detailed picture and can help analyse the integrity of intraocular and facial structures. Magnetic resonance imaging (MRI) is useful but should not be performed if a metallic foreign body is suspected. Electrodiagnostic tests can also be helpful in assessing the integrity of the retina if there is a late presentation.

Treatment will depend on the structures involved and damaged. Primary enucleation is only considered in severe injuries where it is impossible to repair the sclera and there is no prospect of retaining any vision.

Chemical injury

Alkali burns are twice as common as acid burns [12]. Ammonia and sodium hydroxide are most common and can produce severe damage due to rapid penetration.

The diagnosis is obtained directly from the history and patients usually present with an acutely painful red eye with visual loss. Rarely, severe chemical trauma may present pain free, due to significant damage of the superficial nerves.

Chemical eye injury is the only eye injury that requires emergency treatment without formal clinical assessment [13]. Therefore, if seen in primary care, immediately irrigate the eye with water or 0.9% saline. This reduces contact time with the chemical and normalises pH. Ideally, topical anaesthetic should be instilled prior to irrigation to improve comfort and facilitate cooperation. Urgent transfer for ophthalmology assessment should be arranged.

Injuries are graded so appropriate treatment can be given depending on severity. The Roper-Hall grading system considers corneal clarity and the severity of limbal ischaemia [14]. An ophthalmologist may treat milder injuries with topical antibiotics and steroids. Surgery can also be performed to promote revascularisation of the limbus.

Summary

With the increased demand on hospital eye services [15], it is becoming more common to see patients with ophthalmic symptoms in primary care. It is extremely important for General Practitioners and junior doctors rotating through primary care placements to familiarise themselves with the differentials of red eye and to take a clear, thorough and accurate history. This will ensure that serious, potentially sight-threatening conditions are treated correctly and to be urgently referred for specialist opinion.

Acknowledgements

None.

CONFLICTS OF INTEREST

None declared.

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