Scleritis

Scleritis is a severe, potentially vision-threatening inflammation of the sclera — the dense, white fibrous outer coat of the eye. Unlike the superficial episcleral inflammation of episcleritis, scleritis involves the deep episcleral plexus and scleral stroma, producing intense pain, structural scleral damage, and, in approximately 50% of cases, an identifiable underlying systemic autoimmune or infectious disease.

The condition predominantly affects adults in the fourth to sixth decades of life, with a female preponderance (female-to-male ratio approximately 1.6:1). Annual incidence is estimated at 3.4–6 per 100,000 population. Anterior scleritis accounts for roughly 98% of cases; posterior scleritis, though less common, is the most frequently missed diagnosis due to the absence of visible anterior inflammation.

The landmark classification by Watson and Hayreh (1976), refined by Foster (1994), remains the clinical gold standard. Prompt diagnosis and systemic work-up are essential because necrotising scleritis carries up to a 29% risk of vision loss and correlates with systemic vasculitic disease that may be life-threatening if untreated.

Scleritis is broadly divided into immune-mediated and infectious causes, with the majority of cases driven by autoimmune mechanisms.

The sclera is a relatively avascular, collagen-rich structure supplied by the episcleral vasculature. Its low metabolic activity and limited immune surveillance make it vulnerable to immune complex deposition and delayed hypersensitivity reactions.

In immune-mediated scleritis, the central mechanism is a Type III (immune complex–mediated) and Type IV (delayed-type) hypersensitivity response. Circulating immune complexes — often containing IgG, IgM, and complement components — deposit within the walls of episcleral and scleral blood vessels, triggering complement activation and neutrophil recruitment. The resulting vasculitis produces ischaemia, collagen destruction, and granuloma formation.

Histologically, scleritis demonstrates zonal granulomatous inflammation with a central area of collagen necrosis surrounded by palisading epithelioid histiocytes, multinucleated giant cells, lymphocytes (predominantly CD4+ T-cells), and plasma cells. This differs fundamentally from episcleritis, which shows only a non-granulomatous, predominantly lymphocytic infiltrate without scleral collagen destruction.

In necrotising scleritis, progressive small-vessel obliteration leads to ischaemic necrosis of the scleral stroma. The resulting scleral thinning permits the underlying dark uveal tissue to become visible (scleromalacia) and, in advanced cases, risks uveal prolapse or globe perforation. Matrix metalloproteinases (MMPs), particularly MMP-1 and MMP-9, play a key role in scleral collagen degradation.

In posterior scleritis, inflammatory thickening of the posterior sclera and exudative fluid accumulation in Tenon's space produces the characteristic ultrasonographic "T-sign." This can elevate the overlying choroid and retina, causing exudative retinal detachment, choroidal folds, and optic nerve oedema.

The Watson–Hayreh (1976) classification, as refined by Foster (1994), is the most widely used system. Scleritis is divided into anterior and posterior types, with anterior further sub-classified.

• Systemic autoimmune disease — RA, GPA, SLE, relapsing polychondritis, IBD, ankylosing spondylitis; the strongest identifiable risk factor
• Female sex — approximately 60% of scleritis cases occur in women, mirroring the sex predilection of associated autoimmune conditions
• Age 40–60 years — peak age of onset, though any age can be affected
• Prior ocular surgery — pterygium excision (especially with mitomycin C), strabismus surgery, scleral buckling; risk of SINS
• Prior or active herpes zoster ophthalmicus — risk of post-herpetic necrotising scleritis persists years after acute VZV infection
• Active or latent tuberculosis — particularly relevant in high-prevalence regions (Southeast Asia, South Asia, Sub-Saharan Africa)
• Immunosuppression — paradoxically, steroid taper without adequate systemic immunosuppression may trigger rebound scleritis
• Prior episode of scleritis — approximately 30–45% of patients experience recurrence; bilateral involvement occurs in up to 45% overall
• Geographic and ethnic factors — TB-related scleritis more prevalent in Asia; GPA-associated scleritis more common in Northern European populations

Pain is the cardinal and most diagnostically distinguishing symptom of scleritis. It is characteristically described as:

• Severe, boring, deep aching pain — often described as "drilling" or "gnawing"; felt within the orbit and globe, not merely on the ocular surface
• Radiation to adjacent structures — pain classically radiates to the temple, forehead, jaw, or cheek via trigeminal nerve distribution; may be confused with sinusitis, dental pain, or migraine
• Nocturnal exacerbation — pain frequently wakes the patient from sleep, a feature rarely seen in episcleritis
• Tenderness to gentle palpation — pressing on the closed eyelid over the affected scleral zone reproduces the pain; this can help localise posterior scleritis
• Lacrimation and photophobia — secondary to uveal involvement and corneal exposure
• Blurred vision — secondary to corneal astigmatism from scleral distortion, anterior uveitis, exudative retinal detachment (posterior scleritis), or cataract
• Proptosis and diplopia — in posterior scleritis; caused by orbital oedema, restricted motility, or scleral mass effect
• Scleromalacia perforans exception — this subtype is characteristically painless despite severe structural involvement

• Vision loss — occurs in up to 14% of diffuse/nodular and 29% of necrotising scleritis; caused by corneal involvement, cataract, uveitis, glaucoma, or posterior segment complications
• Scleral thinning and staphyloma — progressive thinning may lead to ectatic scleral bulging (staphyloma); the underlying dark uveal tissue becomes visible through the thinned sclera
• Scleral perforation — rare but catastrophic complication of necrotising scleritis or scleromalacia perforans; may occur spontaneously or after minor trauma; requires emergency ophthalmological management
• Peripheral ulcerative keratitis (PUK) — corneal melting at the peripheral margin; strongly associated with systemic vasculitis; may progress to corneal perforation independently
• Anterior uveitis — secondary iritis, posterior synechiae formation, secondary angle-closure glaucoma
• Secondary glaucoma — from uveitic trabecular dysfunction, anterior synechiae, or steroid-induced IOP elevation
• Exudative retinal detachment — primarily in posterior scleritis; resolves with adequate anti-inflammatory treatment
• Choroidal folds and disc oedema — posterior scleral thickening deforms the choroid and optic nerve; may cause metamorphopsia and reduced visual acuity
• Macular oedema and cystoid macular oedema (CMO) — secondary inflammatory involvement
• Posterior subcapsular cataract — from chronic inflammation and/or systemic corticosteroid use

Approximately 50% of scleritis cases are associated with an underlying systemic disease. In necrotising scleritis, this rises to over 90%. Recognition of systemic disease is critical because untreated vasculitic conditions — particularly GPA — carry significant morbidity and mortality independent of ocular involvement.

In Asia, tuberculosis-related scleritis warrants heightened consideration. Singapore's historically high TB prevalence means that all new scleritis cases, particularly nodular or granulomatous presentations, should include latent and active TB screening as part of the systemic work-up.

Prognosis is highly dependent on the subtype of scleritis and the presence and nature of the underlying systemic disease.

• Diffuse anterior scleritis — generally good prognosis; most cases resolve with appropriate NSAID or steroid treatment; recurrence rate approximately 30%; vision loss uncommon
• Nodular anterior scleritis — intermediate prognosis; slower resolution than diffuse form; recurrence common; scleral thinning may persist at nodule sites; vision preservation in the majority
• Necrotising scleritis with inflammation — worst prognosis among anterior subtypes; vision loss in up to 29%; scleral perforation risk; outcome strongly influenced by timely systemic immunosuppression; if untreated systemic vasculitis is present, 5-year mortality was historically reported at 24% (similar to post-myocardial infarction mortality)
• Scleromalacia perforans — progressive structural loss despite absence of pain or inflammation; visual outcome dependent on degree of astigmatic distortion and risk of spontaneous perforation; no proven effective medical treatment once necrosis is established
• Posterior scleritis — generally good visual prognosis if diagnosed early and treated promptly; exudative retinal detachment typically resolves with systemic anti-inflammatory therapy; misdiagnosis or delay worsens outcomes significantly
• Bilateral involvement — occurs in approximately 45% of patients over the disease course; bilateral necrotising scleritis carries an extremely guarded prognosis

Long-term follow-up is essential for all scleritis patients, particularly for monitoring disease recurrence, progressive scleral thinning, secondary glaucoma, and the emergence or progression of systemic disease.

• Pain is the key differentiator. Deep, boring, nocturnal ocular pain that radiates to the face and wakes the patient from sleep is virtually pathognomonic of scleritis. Episcleritis is either painless or mildly uncomfortable.
• Assess the hue in natural light. The bluish-violet discolouration of scleritis is best appreciated in natural daylight or under a broad-spectrum lamp; sodium-based room lighting can mask the colour difference.
• Phenylephrine blanching distinguishes the planes. A simple, reliable in-clinic test: instil phenylephrine 2.5%; near-complete blanching = episcleritis; persistent deep injection = scleritis.
• Posterior scleritis is the great masquerader. Always suspect it when a patient has unexplained deep ocular pain, proptosis, exudative RD, or choroidal folds without an obvious anterior cause. A B-scan ultrasound is mandatory.
• Scleromalacia perforans is painless but dangerous. The absence of pain does not imply a benign course — progressive avascular necrosis risks spontaneous perforation.
• Investigate every case systemically. Even apparently isolated non-necrotising scleritis may be the first presentation of an underlying vasculitic or autoimmune condition. A minimum systemic work-up panel should be ordered at first presentation.
• TB must be excluded before starting systemic steroids in Singapore. Starting corticosteroids in undiagnosed active TB can cause catastrophic disease dissemination. Screen with Quantiferon-TB Gold or Mantoux before systemic anti-inflammatory therapy.
• Do not prescribe periocular steroids in infectious scleritis. Sub-Tenon triamcinolone in viral (HZO) or bacterial (SINS) scleritis can dramatically worsen the infection and precipitate scleral necrosis.
• Bilateral or recurrent scleritis demands systemic immunosuppression. Repeated steroid courses without disease-modifying anti-rheumatic drugs (DMARDs) or immunosuppressants lead to cumulative scleral damage and systemic steroid toxicity.
• Co-manage with rheumatology. Any patient with necrotising scleritis, bilateral disease, or a confirmed systemic association warrants early rheumatology or internal medicine co-management to direct systemic therapy and reduce the risk of systemic disease complications.