Scleritis and Episcleritis

Episcleritis¹

Refers to the common and usually benign condition characterised by inflammation of the episclera, which lies between the conjunctiva and the sclera. It is usually an idiopathic condition but may occasionally occur in the context of underlying disease or exogenous inflammatory stimuli (see below).

The exact prevalence unknown (as many patients probably do not present), but it occurs most frequently in younger patients: young adult to fifth decade and is thought by some to be more common in women.

The most common form is simple episcleritis which is a recurring but self-limiting inflammation affecting part (simple sectoral episcleritis) or all (simple diffuse episcleritis) of the episclera lasting 7-10 days before spontaneously resolving.

Less commonly, nodular episcleritis occurs. This is more severe than simple episcleritis and takes longer to resolve. It is also much more likely to be associated with systemic disease (see below).

Episcleritis does not progress to true scleritis.

Scleritis²

Refers to the generally much more severe inflammation that occurs throughout the entire thickness of the sclera.

This is rare, of the order of 0.1% of presentations in the emergency eye clinic, occurring very slightly more frequently in women and generally in an older age group than patients with episcleritis, with a mean age of presentation of 52 years.

It is classified according to which part of the sclera is affected. It may be anterior (98% of cases) or posterior (2% of cases) and there are 4 clearly recognisable groups of the anterior form:

• Diffuse anterior - this is the most common (and benign) form characterised by widespread inflammation of the anterior sclera. It accounts for about 94% of scleritis cases.
• Nodular - there are erythematous, tender, fixed nodules which, in 20% of cases, progress onto necrotising scleritis.
• Necrotising - this condition is characterised by extreme pain and marked scleral damage; it is usually associated with underlying systemic disease. Where there is associated corneal inflammation, this is also known as sclerokeratitis.
• Scleromalacia perforans - this is also known as necrotising anterior scleritis without inflammation and is notable for its lack of symptoms. It is most frequently associated with rheumatoid arthritis.

• Episcleritis/scleritis
• Uveitis
• Conjunctivitis
• Contact lens related problem

Posterior scleritis has a more extensive list of differential diagnoses including:⁶

• Optic neuritis
• Retinal detachment
• Tumours of the choroid
• Orbital inflammatory disease/mass
• Uveal effusion syndrome
• Harada disease
• Intraocular lymphoma

Investigations

A simple case of episcleritis need not be investigated once a thorough history is taken and examination is carried out to rule out the unlikely possibility of an associated systemic disease (see below). If there is a suspicion, biochemical tests should be performed as guided by concern (e.g. antinuclear antibody, rheumatoid factor, serum uric acid levels etc).

Associated diseases^6,3

• This condition is most commonly idiopathic but 30% is associated with underlying systemic disease.¹
• The most commonly associated systemic disorders are inflammatory bowel diseases: ulcerative colitis and Crohn's disease.⁴
• Connective tissue disease such as rheumatoid arthritis, polyarteritis nodosa, systemic lupus erythematosus and Wegener's granulomatosis have also been associated with recurring episcleritis.
• Infectious causes are less common but known, including herpes zoster virus, herpes simplex virus, Lyme disease, syphilis, hepatitis B and Brucellosis.⁷
• Miscellaneous associations include gout, rosacea, atopy, lymphoma⁸ and thyroid eye disease. A foreign body or chemicals may also cause episcleritis.¹
• There are some very rare but documented associations with a number of other conditions including T-cell leukemia, paraproteinaemia, paraneoplastic syndromes, Wiskott-Aldrich syndrome, adrenal cortical insufficiency and progressive hemifacial atrophy.¹

Management³

• This is treated with artificial tears alone if symptoms are mild.⁹
• Where the episode is more severe, a short course of intensive steroids may be required (under ophthalmologist supervision) and nodular episcleritis may respond best to oral NSAIDs.⁴
• It is important to review these patients (a week after initial presentation is adequate) to ensure resolution of symptoms.
• If the episode is severe, not resolving or if it recurs more than three times, it is appropriate to refer to the Eye Clinic.

Complications

Involvement of ocular structures is rare: there may occasionally be corneal involvement (in the form of inflammatory cell infiltrates or oedema) and recurrent attacks over a period of years may induce some degree of slight scleral thinning. Complications more commonly occur in those patients who have frequently and repeatedly need to resort to topical steroid treatment over a number of years and include cataract formation, ocular hypertension and steroid-induced glaucoma.

Prognosis¹

This tends to resolve fully over 1-2 weeks but patients should be aware that episodes may recur in the same or the fellow eye. If this occurs, it tends to happen at 1-3 monthly intervals.¹³ The treatment-related complications are the commonest cause of visual impairment in these patients (hence the need to recognise the benign nature of this disease and not to overtreat).¹⁰

Investigations

Every effort should be made to rule out associated ocular or systemic pathology (see below). Depending on clinical suspicion, biochemical tests (e.g. full blood count and inflammatory markers, rheumatoid screen, syphilis screen), ultrasonography of the globe, plain X rays (chest and sacroiliac joints), MRI or CT imaging (sinuses and orbits) may be indicated.

The frequency of association and the severity of these associated problems means that it has to be assumed that there is an underlying cause until proven otherwise.⁵ In a patient with no previously diagnosed systemic disease, it is important to rule out systemic vasculitis as this is the least likely to have been previously diagnosed and it is a potentially life-threatening disorder.¹¹

Usually, these investigations will be carried out jointly between the ophthalmologists and other relevant hospital specialists, particularly the rheumatologists.

Associated diseases¹⁰

• At least 50% of these patients have a underlying systemic disease and in 15% of cases, the scleritis is the first presentation of a collagen vascular disorder, preceding it by one to several months.²
• Scleritis is frequently associated with connective tissue diseases of which rheumatoid arthritis is by far the most common. Other connective tissue diseases seen are Wegener's granulomatosis, relapsing polychondritis, systemic lupus erythematosus, Reiter's syndrome, polyarteritis nodosa and ankylosing spondylitis.
• Other common associations include gout, Churg-Strauss syndrome and syphilis.
• It may occur following ocular surgery.¹² The aetiology is not exactly known but it tends to present as intense inflammation adjacent to the surgical site, usually within 6 months of the procedure. There is an association with the presence of underlying disease.
• Less common associations include tuberculosis and local infections (usually spreading from a corneal ulcer) - common culprits are P. aeruginosa, Strep. pneumoniae, Staph. aureus and varicella zoster. It may also occur with Lyme disease. Fungal scleritis is very rare.
• More unusual causes include sarcoidosis, hypertension, parasitic infestation, lymphoma⁸ and trauma¹³ or the presence of a foreign body. It has also been reported in patients taking bisphosphonates² although the causality has been recently questioned.¹⁴

Management

If you suspect scleritis, make an immediate referral to the ophthalmologists.

• Management will depend on the type of scleritis and on whether there is any underlying systemic disease. These patients should all be under specialist care (usually co-managed by the ophthalmologists and rheumatologists).
• Generally, non-necrotising anterior scleritis will be treated with a progressive combination of oral NSAIDs (e.g. ibuprofen 400 mg q.d.s.) then oral prednisolone (e.g. 80 mg o.d.) or a subconjunctival steroid injection such as triamcinolone acetonide (although this is contra-indicated in necrotising scleritis and, some say, should be contra-indicated in scleritis altogether³) ± immunosuppressive therapy such as methotrexate. It may take several weeks to adjust the treatment to produce a satisfactory result.
• Surgery may be carried out for a diagnostic biopsy and can be required to address complications such as cataract formation and intractable glaucoma (see below).
• Necrotising anterior scleritis is managed with systemic steroids and immunosuppressive therapies and may need surgical intervention if perforation is impending.¹⁰ Rituximab has been tried with success but only in a very small number of patients to date.¹⁵
• Treatment has very limited effect in scleromalacia perforans^5,6 but abundant lubrication may also be added to the regimen.
• Management of posterior scleritis is a little more controversial: young patients usually respond well to oral NSAIDs⁶ but elderly patients with associated disease are managed as with anterior non-necrotising scleritis.
• All patients with scleritis should have any underlying disease addressed.

Complications¹⁰

• Scleral thinning
• Ischaemia of the anterior segment of the globe
• Raised intraocular pressure
• Retinal detachment
• Uveitis
• Cataract
• Phthisis (globe atrophy)

Prognosis

Generally, when scleritis originates from a systemic disorder, its course follows that of the underlying problem.² However, anterior necrotising scleritis with inflammation is the most severe and distressing form of the disease. Most patients have an associated vascular disease. Where there is non-necrotising scleritis, the visual prognosis is usually reasonable providing that there are no ocular complications (e.g. uveitis). Otherwise, visual prognosis is poor. There is a mortality rate related to the underlying condition of ~ 25% within 5 years of the onset of scleritis.⁶ Posterior scleritis in patients over 50 is associated with an increased risk of harbouring systemic disease and suffering visual loss.

There are no clear cut prevention measures other than the rigorous control of the progression of any underlying disease and early treatment of the scleritis to minimise the risk of visual loss.