Episcleritis

Idiopathic (Most Common)

The majority of episcleritis cases — approximately 66–70% — have no identifiable underlying systemic cause and are classified as idiopathic. In Watson and Hayreh’s original series, idiopathic disease accounted for the largest single diagnostic category. Idiopathic episcleritis tends to follow a benign recurrent course with episodes lasting days to a few weeks. The absence of systemic association does not negate the need for systemic enquiry, particularly in recurrent or bilateral cases.

Systemic Inflammatory Diseases

• Rheumatoid arthritis (RA): The most frequently associated systemic condition; episcleritis occurs in approximately 0.5–1% of RA patients; may precede articular disease by months to years; tends to correlate with disease activity; nodular episcleritis is more common in seropositive RA
• Inflammatory bowel disease (IBD): Crohn’s disease and ulcerative colitis — episcleritis is one of the most common extra-intestinal manifestations, occurring in up to 3–5% of IBD patients; episodes often (but not always) parallel gut disease flares; may be the first presenting feature of undiagnosed IBD
• Systemic lupus erythematosus (SLE): Episcleritis is a recognised ocular manifestation; tends to be associated with active systemic disease; patients may develop the full spectrum from simple episcleritis to necrotising scleritis
• Ankylosing spondylitis: HLA-B27-associated spondyloarthropathy; episcleritis less common than anterior uveitis in this context but well-documented
• Reactive arthritis (formerly Reiter syndrome): Triad of urethritis, arthritis, and conjunctivitis/episcleritis; Chlamydia trachomatis or enteric organism trigger; HLA-B27 association
• Psoriatic arthritis: Peripheral arthritis with psoriasis; episcleritis documented in the spectrum of psoriatic eye disease

Metabolic and Crystal Deposition Diseases

• Gout (hyperuricaemia): Urate crystal deposition in episcleral tissue triggers an acute inflammatory response; gout-associated episcleritis may coincide with articular gout flares; a careful dietary and medication history is relevant
• Thyroid eye disease (Graves ophthalmopathy): Episcleritis documented in association with thyroid orbitopathy; the episcleral inflammation may reflect the generalised orbital and periocular immune activation
• Atopy: Atopic dermatitis and allergic conditions are associated with a modestly elevated risk of episcleral inflammation, possibly through mast cell and eosinophil-mediated mechanisms

Infectious Causes

• Herpes zoster ophthalmicus (HZO): Varicella-zoster virus reactivation in the ophthalmic division of the trigeminal nerve; episcleritis may accompany the acute dermatomal rash and conjunctivitis; a careful search for periocular vesicles is mandatory in any episcleritis presentation
• Herpes simplex virus (HSV): Less common than HZO; sectoral episcleritis may accompany HSV keratitis; recurrent unilateral episcleritis should prompt consideration of herpetic aetiology
• Lyme disease (Borrelia burgdorferi): Episcleritis documented in early disseminated Lyme disease; tick exposure history and skin lesions (erythema migrans) provide context
• Syphilis (Treponema pallidum): Secondary and tertiary syphilis; interstitial keratitis accompanied by episcleritis; rising syphilis prevalence in many urban populations makes this an increasingly important consideration
• Tuberculosis (Mycobacterium tuberculosis): Episcleral involvement in TB typically reflects hypersensitivity to mycobacterial antigens rather than direct infection; phlyctenular keratoconjunctivitis and episcleritis may occur
• Rosacea: Ocular rosacea is strongly associated with episcleritis and marginal keratitis; patients may have minimal facial skin changes; meibomian gland dysfunction and posterior blepharitis are co-morbid

Other Causes

• Vasculitic conditions: Granulomatosis with polyangiitis (GPA / Wegener’s), polyarteritis nodosa, and other ANCA-associated vasculitides; episcleritis may be an early harbinger; progression to necrotising scleritis or orbital involvement possible
• Sarcoidosis: Systemic granulomatous inflammation; episcleritis is an uncommon but recognised ocular manifestation; associated uveitis, optic nerve granuloma, and lacrimal gland enlargement
• Drug-induced: Bisphosphonates (alendronate, pamidronate), topiramate, and certain biologics have been associated with episcleral inflammation; medication review is important in recurrent or treatment-refractory episcleritis

Anatomical Substrate

The episclera is a thin (approximately 0.3–0.5 mm), richly vascularised layer of loose connective tissue composed of collagen, elastic fibres, fibroblasts, and an extensive vascular plexus. It lies between the bulbar conjunctiva (superficially) and the scleral stroma (deeply), and is attached loosely to Tenon’s capsule anteriorly. The episcleral vascular network consists of two layers: a superficial episcleral plexus (SEP) running in a radial orientation from the limbus toward the equator, and a deeper episcleral plexus. The SEP is the primary site of inflammation in episcleritis and is responsible for the characteristic bright red, radially arranged vessels visible clinically. By contrast, scleritis involves the deeper scleral stroma and scleral vessels, producing the deeper, violaceous discolouration and severe pain characteristic of that condition.

Inflammatory Mechanism

1. Immune complex deposition: The prevailing hypothesis for episcleritis pathogenesis involves immune complex (antigen–antibody complex) deposition in the walls of episcleral vessels. In systemic inflammatory diseases, circulating immune complexes (e.g., rheumatoid factor / IgG complexes in RA) are deposited in the episcleral microvasculature, activating the complement cascade (C3a, C5a) and triggering neutrophil recruitment
2. Complement activation: C5a acts as a potent chemotactic factor for neutrophils and eosinophils; C3a causes mast cell degranulation; together they produce the localised vascular dilation, increased permeability, and cellular infiltration characteristic of acute episcleral inflammation
3. Vasodilation and vascular permeability: Histamine, prostaglandins, and leukotrienes released by activated mast cells and recruited inflammatory cells produce dilation of the superficial episcleral plexus; this produces the bright red colour and warmth of the episcleral vessels; the superficial nature of the inflammation (above the deep scleral plexus) explains why pain is mild — deep scleral nerve fibres are not significantly involved
4. Cellular infiltrate: Histopathological examination of episcleritis specimens demonstrates a perivascular infiltrate predominantly of lymphocytes, plasma cells, and macrophages, with variable neutrophil contribution in acute phases; eosinophils may be present in atopy-associated cases; granulomatous infiltrate (epithelioid cells, giant cells) is seen in sarcoidosis and TB-associated disease
5. Nodule formation (nodular episcleritis): Persistent antigen stimulation in nodular episcleritis drives progressive fibroblast activation and collagen deposition around an inflammatory cell nidus, producing a discrete, firm, mobile, tender nodule on the episcleral surface; the nodule can be moved separately from the overlying conjunctiva but is fixed to the underlying episclera, distinguishing it from conjunctival cysts or papillae

Why Episcleritis Is Self-Limiting

The episclera lacks the rigid structural components and the dense innervation of the sclera, and its loose connective tissue architecture allows inflammatory oedema to dissipate relatively quickly. Anti-inflammatory cytokines (IL-10, TGF-β), regulatory T-cell activity, and natural resolution of the triggering immune complex load contribute to spontaneous resolution within days to weeks. The absence of significant complement activation in the deep scleral stroma accounts for the benign, self-limiting natural history distinguishing episcleritis from the progressive, destructive inflammation of scleritis.

Watson and Hayreh Classification (1976)

By Distribution

• Sectoral (most common): Confined to one or two clock-hour sectors, most frequently the interpalpebral (temporal or nasal) quadrant between the 3 and 9 o’clock positions; the remainder of the sclera appears white and uninflamed
• Diffuse: Generalised involvement of the entire bulbar episclera; less common than sectoral; more likely to be associated with systemic disease; may be confused with diffuse conjunctivitis on cursory examination

Comparison with Scleritis

Demographic and Baseline Factors

• Sex: Episcleritis shows a slight female predominance (approximately 60% female in most published series), potentially reflecting the higher prevalence of autoimmune diseases in women
• Age: Peak incidence in the third to fifth decades; occurs across all age groups including children (though less common); nodular episcleritis tends to present in an older demographic than simple episcleritis
• Pre-existing systemic autoimmune disease: Patients with established RA, IBD, SLE, or other connective tissue diseases are at significantly elevated risk; ocular manifestations may herald or parallel systemic flares
• Previous episodes: A history of prior episcleritis is the strongest individual predictor of recurrence; approximately 30–40% of patients will experience recurrent episodes; nodular disease recurs more frequently than simple

Modifiable and Contextual Risk Factors

• Inadequately controlled systemic inflammatory disease: Uncontrolled RA, IBD in active flare, or SLE with elevated disease activity are associated with higher risk of episcleral involvement
• Bisphosphonate therapy: Oral and intravenous bisphosphonates used for osteoporosis and bone metastases (alendronate, pamidronate, zoledronate) are a well-documented drug cause; review of medication history is important
• Rosacea: Undiagnosed or undertreated facial rosacea is a common and frequently overlooked cause of recurrent episcleritis; enquiry about facial flushing, erythema, and rhinophyma is relevant
• Dietary triggers (gout): High purine diet, alcohol, and dehydration precipitate gout flares and may trigger gout-associated episcleral attacks
• Viral reactivation: Psychological stress, UV exposure, febrile illness, and immunosuppression are known triggers for HSV and HZV reactivation and their associated episcleral inflammation

External Examination

• Sectoral or diffuse episcleral injection: The defining clinical sign; characteristically bright red (not the violaceous or purple-red of scleritis); confined to the episcleral vascular plexus; sectoral disease occupies one to two quadrants, most commonly temporal; diffuse involvement covers the entire anterior bulbar surface
• Radially oriented episcleral vessels: Episcleral vessels run in a radial (spoke-like) pattern from the limbus toward the equator; they are larger and fewer in number than the fine branching vessels of the conjunctival plexus; on slit lamp examination, vessels overlie the white sclera and can be seen to be slightly elevated above the scleral surface
• Vessel mobility: Episcleral vessels move with the overlying conjunctiva when the conjunctiva is displaced with a cotton bud; this mobility distinguishes episcleral from deep scleral vessels, which are fixed — a critical bedside test
• Preserved white sclera outside the affected sector: The uninflamed scleral quadrants remain white and uninvolved — a reassuring sign; diffuse scleritis by contrast involves the entire scleral circumference
• Localised chemosis: Mild localised conjunctival oedema overlying the inflamed episcleral sector may be present, particularly in diffuse episcleritis
• Epiphora: Reflex lacrimation from ocular surface irritation; tear film may appear unstable over the inflamed sector

Nodular Episcleritis — Additional Signs

• Discrete raised nodule: Single (occasionally multiple) palpable, tender, firm-to-rubbery nodule on the episcleral surface; typically 2–4 mm in diameter; located most often in the interpalpebral zone, temporal or nasal to the limbus
• Nodule mobility: The nodule moves with the episclera but slides freely under the overlying conjunctiva (cannot be moved independently of the episclera); this distinguishes it from conjunctival cysts (freely mobile), pinguecula (fixed to conjunctiva), and scleral nodules (immobile)
• Surrounding injection halo: Hyperaemic ring of episcleral vessels surrounding the nodule; the “ring sign” of nodular episcleritis

Phenylephrine 2.5% Blanching Test

Instillation of one drop of phenylephrine 2.5% (or 10%) produces vasoconstriction of the superficial episcleral plexus within 10–15 minutes. In episcleritis, the vessels blanch significantly or completely, revealing normal white sclera beneath. In scleritis, the deeper scleral vessels — which are less responsive to adrenergic stimulation — do not blanch, and the residual violaceous discolouration of the underlying scleral stroma persists. This test is the single most clinically useful bedside manoeuvre to differentiate episcleritis from scleritis and should be performed in all cases where the diagnosis is uncertain.

Slit Lamp Findings

• Anterior chamber: Quiet — no cells or flare in uncomplicated episcleritis; presence of AC activity raises concern for concurrent anterior uveitis and warrants reconsideration of the diagnosis (scleritis, HZO)
• Cornea: Typically clear; mild superior SPK may occur from tear film disruption; marginal infiltrates in rosacea-associated episcleritis; frank keratitis should prompt consideration of HZO or HSV
• Lens: Clear; no posterior segment involvement expected
• Sclera: No thinning or translucency — scleral thinning (producing a blue-grey discolouration from choroidal show-through) is a feature of necrotising or posterior scleritis, not episcleritis

Characteristic Symptom Profile

• Acute redness of the eye: Typically the first and most prominent complaint; patients notice sudden or rapidly progressive redness in one sector of the eye, often on waking or during the day; may be alarming in appearance despite being symptomatically mild
• Mild ocular discomfort or tenderness: A dull ache or sense of pressure in or around the eye; tenderness to gentle palpation through the closed eyelid over the inflamed sector; importantly, the pain of episcleritis is characteristically mild — any severe, deep, or radiating pain should redirect the clinician toward scleritis
• Lacrimation (watering): Mild reflex tearing from ocular surface irritation; does not indicate significant tear film pathology in uncomplicated cases
• Mild photophobia: Sensitivity to bright light from episcleral inflammation; significant photophobia or pain on light exposure suggests intraocular involvement (uveitis) or corneal disease and warrants urgent reassessment
• Normal vision: Visual acuity is preserved in uncomplicated episcleritis; any reduction in VA is atypical and mandates exclusion of scleritis, keratitis, or uveitis
• Awareness of a lump (nodular type): Patients with nodular episcleritis may feel or see the raised nodule; tenderness to direct touch over the nodule is characteristic

Symptom Features That Should Prompt Reconsideration of the Diagnosis

Ocular Complications (Generally Uncommon)

• Recurrence: The most clinically significant complication; approximately 30–40% of patients experience recurrent episodes; in some patients, recurrences occur in the same sector each time; frequency and severity may increase with time in systemically associated disease
• Superficial keratopathy: Mild superior or interpalpebral SPK from disrupted tear film over the inflamed sector; usually resolves with the underlying episcleritis; no permanent corneal consequence in isolated episcleritis
• Anterior uveitis (rare in isolated episcleritis): Mild AC cells may occur in association with episcleritis in HZO, syphilis, or sarcoidosis; should prompt a systemic workup if present
• Progression to scleritis (rare): A small proportion of patients initially diagnosed with episcleritis are subsequently found to have, or progress to, anterior scleritis; this risk is higher in the context of RA, GPA, or polyarteritis nodosa; any case with worsening pain, scleral discolouration, or visual change must be urgently reassessed
• Residual pigmentation: Following resolution of nodular episcleritis, mild episcleral pigmentation or thickening may persist; typically of cosmetic significance only

Treatment-Related Complications

• Topical NSAID-related corneal toxicity: Prolonged use of topical diclofenac, ketorolac, or flurbiprofen can produce corneal epithelial erosions and, rarely, corneal melting (particularly in patients with dry eye or after surgery); judicious use limited to acute flare duration is important
• Steroid-induced ocular hypertension and glaucoma: Topical corticosteroid use for episcleritis carries the standard risk of IOP elevation in steroid responders; IOP must be monitored; the use of topical steroids in episcleritis is generally reserved for severe or refractory cases due to this risk and the self-limiting natural history
• Steroid-induced posterior subcapsular cataract: Complication of prolonged topical or systemic corticosteroid therapy; relevant only if steroids are used for extended periods, which is uncommon in episcleritis

Prevalence of Systemic Association

In the most comprehensive published series (Watson and Hayreh 1976, Jabs et al. 2000), systemic disease is identified in approximately 26–36% of all episcleritis patients. The association rate is higher in nodular episcleritis (~50%) than in simple episcleritis (~30%), and higher in bilateral and recurrent disease. A thorough systemic review of systems and targeted investigation is warranted in all but the most straightforward single episode of simple episcleritis, particularly in patients with a personal or family history of autoimmune disease.

Key Systemic Associations and Their Ocular–Systemic Relationships

Diagnostic Approach

The diagnosis of episcleritis is primarily clinical, based on characteristic slit lamp findings combined with the phenylephrine blanching test. The critical diagnostic priority is to distinguish episcleritis from scleritis — which requires urgent systemic investigation and ophthalmological management — and from other causes of acute red eye. No laboratory test is required to diagnose episcleritis itself; investigations are directed at identifying an associated systemic disease.

History

• Onset and duration of redness; unilateral vs. bilateral; previous similar episodes
• Character and severity of pain — mild discomfort vs. deep boring pain (key scleritis discriminator)
• Visual symptoms — any change in visual acuity?
• Systemic review of systems: joint pain/swelling, skin rashes, bowel symptoms, urinary symptoms, respiratory symptoms, facial flushing/skin changes
• Current medications — bisphosphonates, biologics, antiepileptics
• History of systemic autoimmune disease, IBD, gout, thyroid disease, rosacea
• History of cold sores, shingles, or recent viral illness
• Family history of autoimmune disease

Clinical Examination

Laboratory Investigations (Targeted)

Investigations are not required for the diagnosis of episcleritis but are indicated in: recurrent episcleritis; bilateral disease; nodular episcleritis; or when systemic disease is clinically suspected. A reasonable screen for first-presentation recurrent episcleritis includes:

• Full blood count (FBC): Anaemia of chronic disease, leucocytosis in infection, eosinophilia in atopy or vasculitis
• ESR and CRP: Non-specific markers of systemic inflammation; elevated in active RA, IBD, vasculitis
• Rheumatoid factor (RF) and anti-CCP antibodies: RA serology; anti-CCP is more specific; both may be negative in seronegative RA
• ANA and anti-dsDNA: SLE screening
• ANCA (c-ANCA / p-ANCA): Granulomatosis with polyangiitis (PR3-ANCA), microscopic polyangiitis (MPO-ANCA)
• Serum uric acid: Gout workup
• ACE and chest X-ray: Sarcoidosis screen
• Syphilis serology (RPR / TPHA / VDRL): Rising syphilis prevalence warrants inclusion in recurrent unilateral episcleritis workup
• Thyroid function tests (TFT): If thyroid eye disease is clinically suspected
• Urinalysis: Haematuria, proteinuria — vasculitis (GPA, polyarteritis nodosa)

Overall Prognosis

The prognosis for episcleritis is excellent. It is a benign, self-limiting condition that does not threaten vision and does not cause permanent structural ocular damage in the vast majority of cases. Individual episodes of simple episcleritis resolve spontaneously within 7–21 days even without treatment. Nodular episcleritis may take somewhat longer — typically 4–6 weeks — to resolve. The greatest clinical concern is recurrence: approximately 30–40% of patients will experience further episodes, and in those with underlying systemic inflammatory disease, the frequency and severity may increase with systemic disease activity. Long-term vision loss from isolated episcleritis is exceptionally rare and virtually limited to cases that were incorrectly diagnosed and were in fact anterior scleritis.

Prognostic Factors