Loay Nawaz Rahman
Imperial College Healthcare NHS Trust, London, United Kingdom.
Introduction
Episcleritis
Episcleritis is a benign inflammatory condition affecting the episcleral layer, the outermost layer of the sclera of the eye (1). There are two main types of episcleritis, nodular and simple. Nodular episcleritis accounts for 30% of cases and presents with a discrete elevated area of inflamed tissue (nodule) in the episcleral layer surrounded by dilated blood vessels. Simple episcleritis also presents with a red eye and dilated blood vessels but not an elevated area of inflamed tissue. It is subdivided into two groups; diffuse simple episcleritis, where the inflammation is generalised, and sectoral simple episcleritis, where the inflammation is restricted to one region (2).
Scleritis
Scleritis is an inflammatory condition involving the deep scleral layers. As with episcleritis, it can also present with a red eye but the condition is more severe. Scleritis is subclassified into two main groups; anterior scleritis (affecting 90% of cases) and posterior scleritis (10%).
Anterior scleritis is the most common subtype and is defined as scleral inflammation that occurs anteriorly to the extraocular recti muscles. It is split into two further subtypes, non-necrotising anterior scleritis (accounting for 75% of scleritis cases), and necrotising anterior scleritis (15%). The two main types of non-necrotising scleritis includes diffuse anterior scleritis, the most common type of scleritis which presents with anterior scleral oedema and dilation of deep episcleral vessels, and nodular anterior scleritis, which presents with distinct nodules of scleral oedema that may be tender on palpation. Necrotising anterior scleritis on the other hand is the most severe form of scleritis which causes severe ocular pain and tenderness and may be associated with inflammation. Scleromalacia perforans is a rare form of necrotising anterior scleritis where there is no associated inflammation and is typically painless. Prognosis for necrotising anterior scleritis is poor as severe vasculitis can lead to scleral necrosis and exposure of the choroid, with a degree of visual impairment occurring in 75% of patients at some point.
Posterior scleritis is the least common form of scleritis and refers to scleral inflammation that occurs posteriorly to the insertion of the extraocular recti muscles. Clinical features may include vision loss and pain on eye movement, as well as serous retinal detachment and choroidal folds (striae in the fundus) on slit lamp microscopy (3).
Risk Factors
Episcleritis presents in women between 20 to 50 years old, with the majority of cases being idiopathic. It can present unilaterally or bilaterally, the latter accounting for approximately 50% of cases. Scleritis is also more common in women typically presenting between the ages of 40 and 60 years. Infectious scleritis is more common in men, and bilateral scleritis is most commonly associated in patients with rheumatic disease. Surgically induced scleritis may occur in patients who have had two or more previous ocular surgeries (3).
Pathophysiology
Episcleritis
The inflammation in episcleritis is mediated by activation of immune cells such as macrophages and lymphocytes. Most cases are idiopathic but a third may be associated with a systemic disease where episcleritis may be its first presenting feature. These include systemic vasculitides such as granulomatosis with polyangiitis (GPA), polyarteritis nodosa and Behçet’s disease, inflammatory diseases such as rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, gout, ulcerative colitis and Crohn’s disease. There may be an infectious cause that can be bacterial, viral or fungal in origin. Occasionally, eyes exposed to chemicals or foreign bodies may trigger episcleritis (4).
Scleritis
Scleritis may be idiopathic, but 50% of cases can be associated with the systemic diseases mentioned above. In all cases, there is scleral oedema and inflammation. If scleritis is associated with an autoimmune disorder, there may be zonal scleral necrosis surrounded by a granulomatous inflammation containing eosinophilic fibrinoid matter. In cases of idiopathic necrotising scleritis, there may be a small area of scleral necrosis with non-granulomatous inflammation mediated by mononuclear cells such as lymphocytes, plasma cells and macrophages (3).
Clinical Presentation
Episcleritis typically presents with a red eye due to engorgement of large episcleral blood vessels, and watery eyes (1). It is typically painless but can occasionally present with mild pain that can have an acute or gradual onset. There may be associated globe tenderness. Normally, visual acuity remains unchanged. Diffuse simple episcleritis may present with a red appearance throughout the sclera, whereas the redness is limited to a particular area in sectoral simple episcleritis. In nodular episcleritis there is redness in a small defined area along with a nodule (area of inflamed tissue), and may be more painful than simple episcleritis (2).
Conversely, scleritis presents with a unilateral red eye and severe deep ocular pain that may radiate to the jaw or the temple, alongside photophobia, tearing, reduced visual acuity and globe tenderness. The pain develops gradually over days and is typically worse at night and is more severe than in episcleritis (5).
Differentiating between episcleritis and scleritis
On slit lamp examination, inflamed vessels are seen in both episcleritis and scleritis. The vessels in scleritis are more tortuous and cannot be moved using a cotton tipped applicator, as opposed to in episcleritis where the vessels are more superficial and can be displaced. Another common method to differentiate between the two conditions is by applying 2.5-10% phenylephrine drops. In episcleritis, the vessels blanch whereas the deeper scleral vessels in scleritis do not.
Nodular episcleritis and scleritis present similarly with an elevated areas of inflamed tissue (nodules) but can be differentiated using the narrow-slit lamp beam. In nodular episcleritis, the inner reflection of the beam remains on the scleral layer whilst the outer layer is displaced, whereas in scleritis, both the inner and outer reflections are displaced from the scleral layers (6).
Other features of scleritis include a blue tinge with scleral oedema and dilatation. Sometimes, there may be evidence of keratitis with corneal infiltrates. Posterior scleritis can present with choroidal folds, serous retinal detachment and optic nerve oedema.
Systemic disease involvement
In both episcleritis and scleritis, it is important to conduct a full physical examination to look for signs of associated systemic diseases. For example, there may be skin nodules or arthritic changes highlighting that rheumatoid arthritis may be a possible underlying cause, or a history of epistaxis, sinusitis and haemoptysis may suggest GPA as a cause (6).
Investigations
Both episcleritis and scleritis are clinical diagnoses highlighting the importance of thorough history taking and examination. Investigations instead target identifying an underlying cause. Recurrent episodes of episcleritis may warrant investigation for systemic diseases if there is no existing history. These include a full blood count, investigating the presence of systemic disease blood markers such as rheumatoid factor, antinuclear antibody, serum uric acid and erythrocyte sedimentation rate (ESR), and a chest x-ray. Similar investigations are conducted for scleritis, and cross-sectional imaging may be beneficial if there is posterior segment involvement (3).
Differentials
There are a wide range of differentials when a patient presents with an acute red eye. Alongside episcleritis and scleritis, other differentials include conjunctivitis (bacterial, viral or allergic), anterior uveitis, acute angle closure glaucoma, corneal ulcers, chemical injuries, trauma and endophthalmitis. Clinical assessment through history taking and examination are essential to differentiate between these causes (7). Scleritis requires same day referral to an ophthalmologist (8), whereas episcleritis is referred to an ophthalmologist when further investigation is required; indications include multiple attacks or evidence of systemic disease (9).
Management
Episcleritis
Episcleritis is usually self-limiting and resolves within 7-10 days. Some patients may experience pain which can either be managed conservatively through cold compresses and iced artificial tears or medically with systemic non-steroidal anti-inflammatory drugs (NSAIDs) such as oral ibuprofen, indomethacin or flurbiprofen. Topical steroids such as fluorometholone may be used for 1-2 weeks in severe cases (9, 10). Follow up is not normally indicated in episcleritis except for those on topical steroids who require an intraocular pressure assessment within 7-10 days due to risk of steroid-related ocular hypertension (OHT).
Scleritis
Management depends on the severity and type of scleritis. Patients with mild-to-moderate scleritis may only require oral NSAIDs for analgesia. In cases of necrotising anterior scleritis, posterior scleritis or when NSAIDs are contraindicated, systemic corticosteroids may be considered. Periocular steroid injections may be considered in non-necrotising scleritis, but contraindicated in necrotising scleritis. Patients on any form of steroid should be reviewed in 7-10 days due to risk of steroid-related OHT. Immunosuppressive or immunomodulatory medications may be considered if refractory to steroids or if there is evidence of an associated systemic disease, but this is a multidisciplinary team decision usually involving an ophthalmologist and rheumatologist. Finally, topical antibiotics may be beneficial in infective scleritis.
Surgery is uncommon in scleritis but a scleral reinforcement graft may be indicated if there is evidence of scleral perforation or excessive scleral thinning with a high risk of rupture. Additionally, small corneal perforations can form as the disease progresses. A bandage contact lens or corneal glue can be applied to temporarily repair the corneal tissue until the inflammation settles to allow for surgical repair (8, 10).
Complications
Episcleritis
Episcleritis usually self resolves and vision is not typically affected. Recurrent disease may lead to anterior and intermediate uveitis and development of peripheral corneal infiltrates. Steroid use can increase the risk of developing glaucoma or cataracts (3).
Scleritis
Complications are more common in scleritis and increases the risk of developing uveitis, cataract and glaucoma. Sclerokeratitis may also develop, where the peripheral cornea is opacified with fibrous tissue that gradually spreads centrally to opacify a larger area of the cornea, further reducing vision. There is also a risk of developing sclerosing keratitis in anterior scleritis that involves inflammation and injury to the corneal layer adjacent to the site of scleral inflammation. Vitritis, which is the presence of cells and debris in the vitreous, may occur in posterior scleritis. Visual acuity may be lost depending on the severity of disease; mild-moderate disease may not result in vision loss, but untreated scleritis can lead to blindness, especially in necrotising scleritis (3).
References
1. Heath G. The episclera, sclera and conjunctiva: An overview of relevant ocular anatomy. Differential Diagnosis of Ocular Disease. 2006;9(2):36-42.
2. Kunimoto, Derek; Kunal Kanitkar; Mary Makar (2004). The Wills eye manual: office and emergency room diagnosis and treatment of eye disease(4 ed.). Philadelphia, PA: Lippincott Williams & Wilkins. pp. 99–100. ISBN 978-0781742078.
3. Watson P, Hayreh S. Scleritis and episcleritis. British Journal of Ophthalmology. 1976;60(3):163-191.
4. Schonberg S, Stokkermans T. Episcleritis. StatPearls. 2021;
5. Vorvick, Linda J. (July 28, 2010). Scleritis PubMed Health. United States National Library of Medicine. Retrieved 10 January 2022.
6. Sainz de la Maza M, Molina N, Gonzalez-Gonzalez L, Doctor P, Tauber J, Foster C. Clinical Characteristics of a Large Cohort of Patients with Scleritis and Episcleritis. Ophthalmology. 2012;119(1):43-50.
7. NICE. Red eye | Health topics A to Z | CKS | NICE (Internet). NICE CKS. (cited 10 January 2022). Available from: https://cks.nice.org.uk/topics/red-eye/
8. The College of Optometrists. Scleritis. Accessed (Internet). (cited 10 January 2022). Available from: https://www.college-optometrists.org/clinical-guidance/clinical-management-guidelines/scleritis
9. The College of Optometrists. Episcleritis (Internet). (cited 10 January 2022). Available from: https://www.college-optometrists.org/clinical-guidance/clinical-management-guidelines/episcleritis
10. Daniel Diaz J, Sobol E, Gritz D. Treatment and management of scleral disorders. Survey of Ophthalmology. 2016;61(6):702-717.