Ophthalmology – Scleritis

Core Definition

Scleritis is a deep inflammatory disorder of the sclera and adjacent episcleral tissues that can threaten vision and, in severe cases, the structural integrity of the globe.

Typical features include:

• Severe deep ocular pain
• Violaceous scleral redness
• Ocular tenderness
• Possible reduction in vision
• Frequent association with systemic autoimmune disease

Scleritis may be:

• Immune mediated
• Infectious
• Occasionally associated with prior surgery or trauma

Importantly, scleral necrosis occurs only in the more severe necrotizing forms.

Main Clinical Subtypes

Scleritis is broadly divided into:

• Anterior scleritis
• Posterior scleritis

Anterior disease is far more common.

Widespread Anterior Inflammation

Diffuse anterior scleritis is the most common subtype.

Typical findings include:

• Broad area of deep scleral injection
• Violaceous discoloration
• Marked tenderness
• Deep aching or boring pain

It is generally less destructive than necrotizing disease.

Localized Nodular Disease

Nodular anterior scleritis presents with:

• A focal elevated scleral nodule
• Marked tenderness
• Deep vascular congestion
• Severe pain

The nodule is:

Fixed to the sclera and does not move freely

which helps distinguish it from nodular episcleritis.

Destructive Inflammatory Scleritis

Necrotizing scleritis with inflammation is the most severe anterior form.

Features include:

• Extreme ocular pain
• Deep scleral inflammation
• Avascular areas
• Scleral thinning
• Progressive tissue necrosis
• Bluish appearance from increased scleral transparency

Underlying uveal tissue may become visible through severely thinned sclera.

This form should raise urgent concern for:

Systemic vasculitis, especially granulomatosis with polyangiitis.

Painless Necrotizing Disease

Scleromalacia perforans is a form of necrotizing scleritis with little or no visible inflammation.

Typical features include:

• Progressive scleral thinning
• Minimal redness
• Minimal or absent pain

It is classically associated with longstanding:

Rheumatoid arthritis

Despite the name, actual spontaneous perforation is uncommon unless disease is very advanced.

Inflammation Behind the Globe

Posterior scleritis affects the sclera posterior to the equator.

Possible manifestations include:

• Deep pain
• Pain with eye movement
• Reduced vision
• Proptosis
• Restricted motility
• Optic disc edema
• Choroidal folds
• Exudative retinal detachment
• Choroidal thickening

The anterior eye may appear nearly normal, so the diagnosis can be missed.

Typical Patient Profile

Scleritis is uncommon and occurs most often in:

• Adults
• Middle age
• Women more often than men

However, it can occur at any age.

Mechanism of Inflammation

In noninfectious disease, pathogenesis involves:

• Immune-complex injury
• T-cell activation
• Cytokine-mediated inflammation
• Scleral vascular inflammation

Severe disease may progress to:

Occlusive vasculitis and tissue necrosis.

Important Systemic Associations

A substantial proportion of patients have an associated systemic inflammatory disorder.

Important conditions include:

• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Relapsing polychondritis
• Systemic lupus erythematosus
• Spondyloarthritis
• Inflammatory bowel disease
• Sarcoidosis
• IgG4-related disease
• Other systemic vasculitides

Scleritis may occasionally be the:

First clue to previously undiagnosed systemic disease.

Rheumatoid-Associated Scleritis

RA is especially associated with:

• Necrotizing scleritis
• Scleromalacia perforans
• Peripheral ulcerative keratitis

Severe ocular disease in RA may reflect:

Systemic rheumatoid vasculitis.

ANCA-Associated Vasculitic Disease

Granulomatosis with polyangiitis (GPA) is particularly important.

Associated systemic features may include:

• Chronic sinus disease
• Pulmonary symptoms
• Hematuria
• Renal dysfunction

Necrotizing scleritis in this setting requires:

Urgent systemic evaluation and treatment.

Infectious Causes

Although most scleritis is noninfectious, infection must be considered.

Risk factors include:

• Prior ocular surgery
• Pterygium surgery
• Scleral buckle
• Trauma
• Foreign body
• Mitomycin C exposure
• Immunosuppression

Possible organisms include:

• Pseudomonas
• Staphylococcus
• Nocardia
• Mycobacteria
• Aspergillus and other fungi
• HSV
• VZV
• Tuberculosis
• Syphilis

Clues Suggesting Infection

Features that should raise suspicion include:

• Prior surgery or trauma
• Scleral ulceration
• Purulent discharge
• Multifocal scleral abscesses
• Necrosis
• Poor response to corticosteroids
• Worsening after immunosuppression

Infectious scleritis treated with steroids alone may deteriorate rapidly.

Characteristic Pain Pattern

The classic symptom is:

Deep, boring ocular pain

which may radiate to:

• Brow
• Forehead
• Temple
• Cheek
• Jaw

Pain may:

• Wake the patient from sleep
• Worsen with eye movement
• Be disproportionate to the visible redness

Other Symptoms

Patients may also complain of:

• Red eye
• Photophobia
• Tearing
• Blurred vision
• Globe tenderness

Posterior disease may present mainly with:

• Pain
• Reduced vision
• Diplopia

A Notable Exception

Absence of pain does not exclude severe disease.

Scleromalacia perforans may be nearly painless despite extensive scleral thinning.

Typical Appearance on Examination

The sclera often appears:

Deep red to violaceous

rather than bright red.

This reflects involvement of deeper:

• Episcleral vessels
• Scleral vascular plexus

What to Inspect at the Slit Lamp

Examine the sclera in all directions of gaze for:

• Deep injection
• Nodules
• Avascular patches
• Scleral thinning
• Necrosis
• Corneal involvement

Also assess:

• Anterior chamber
• IOP
• Lens
• Peripheral cornea

Why the Cornea Must Be Checked

Scleritis may coexist with:

Peripheral ulcerative keratitis

This combination is particularly concerning for systemic:

• Rheumatoid vasculitis
• ANCA-associated vasculitis

Corneal thinning substantially increases the urgency of treatment.

Associated Anterior Uveitis

Severe scleritis may produce:

• Anterior chamber cells
• Flare
• Posterior synechiae

This generally indicates more extensive ocular inflammation.

Using the Blanching Test

Topical phenylephrine can help distinguish episcleritis from scleritis.

Episcleritis

Superficial vessels usually:

Blanch substantially

Scleritis

Deep vascular congestion:

Persists despite phenylephrine

The test is supportive rather than absolutely diagnostic.

Separating Scleritis From Episcleritis

Scleritis

• Deep severe pain
• Violaceous hue
• Globe tenderness
• Reduced vision possible
• Deep vessels do not blanch
• Strong systemic disease association
• Potentially vision-threatening

Episcleritis

• Mild discomfort
• Bright-red superficial injection
• Vision usually normal
• Superficial vessels blanch
• Usually self-limited

Posterior Segment Assessment

A dilated fundus examination is important, especially when vision is reduced.

Look for:

• Choroidal folds
• Optic disc edema
• Exudative retinal detachment
• Vitritis
• Macular abnormalities

Most Useful Test for Posterior Disease

B-scan ultrasonography is a major diagnostic tool.

Possible findings include:

• Posterior scleral thickening
• Choroidal thickening
• Fluid in the posterior sub-Tenon space

Classic Ultrasound Clue

The characteristic:

T-sign

results from fluid surrounding the optic nerve in the posterior sub-Tenon space.

It supports the diagnosis of posterior scleritis, but:

Its absence does not exclude the disease.

OCT Findings in Posterior Scleritis

OCT may demonstrate:

• Subretinal fluid
• Choroidal folds
• Macular edema
• Increased choroidal thickness

Serial OCT can be useful for monitoring treatment response.

When Cross-Sectional Imaging Is Helpful

MRI or CT may be useful when:

• Posterior scleritis is uncertain
• Orbital disease is suspected
• A mass must be excluded
• Optic nerve involvement is present

MRI may show:

• Scleral thickening
• Enhancement
• Adjacent orbital inflammatory changes

Building the Systemic Work-Up

Laboratory testing should be:

Targeted to the history, phenotype, and severity

rather than identical in every patient.

Useful Baseline Studies

Depending on context, tests may include:

• CBC
• Renal function
• Liver function
• ESR
• CRP
• Urinalysis

These help detect systemic inflammation and occult renal disease.

Testing for ANCA-Associated Vasculitis

When vasculitis is suspected, consider:

• PR3-ANCA
• MPO-ANCA

Also check:

• Creatinine
• Urinalysis

because occult glomerulonephritis may be present.

Evaluating for Rheumatoid Disease

When clinically appropriate, consider:

• Rheumatoid factor
• Anti-CCP antibody

Anti-CCP is especially useful when RA is suspected.

Excluding Important Infections

Testing often includes, when appropriate:

• Syphilis serology
• Tuberculosis screening with IGRA or locally appropriate testing

Additional infectious tests depend on:

• Exposure history
• Surgery
• Travel
• Immunosuppression

Role of Chest Imaging

Chest imaging may be useful when considering:

• Sarcoidosis
• Tuberculosis
• GPA

Chest CT is more sensitive than plain radiography when suspicion remains high.

When Microbiologic Sampling Is Needed

Suspected infectious scleritis may require:

• Scraping
• Culture
• PCR
• Scleral biopsy

particularly with:

• Necrosis
• Abscess formation
• Postoperative disease
• Failure of empiric treatment

Disorders That Mimic Anterior Scleritis

Important alternatives include:

• Episcleritis
• Conjunctivitis
• Peripheral ulcerative keratitis
• Severe keratitis
• Anterior uveitis
• Acute angle-closure glaucoma

Disorders That Mimic Posterior Scleritis

Important alternatives include:

• Choroidal melanoma
• Vogt-Koyanagi-Harada disease
• Uveal effusion syndrome
• Central serous chorioretinopathy
• Choroidal detachment
• Orbital inflammatory disease
• Choroidal metastasis

Overall Treatment Principles

Management depends on:

• Infectious vs noninfectious etiology
• Anterior vs posterior disease
• Presence of necrosis
• Associated systemic disorder
• Severity and visual threat

The goal is:

Rapid suppression of scleral inflammation before irreversible tissue damage occurs.

First Step in Mild Noninfectious Disease

For mild-to-moderate diffuse or nodular anterior scleritis, treatment often begins with:

An oral NSAID

Examples include:

• Ibuprofen
• Naproxen
• Indomethacin

assuming no renal, gastrointestinal, cardiovascular, or other contraindication exists.

Escalating Beyond NSAIDs

Systemic corticosteroid is generally used when there is:

• Persistent severe pain
• Failure of NSAIDs
• Posterior scleritis
• Vision-threatening disease
• Necrotizing inflammation

Systemic Corticosteroid Therapy

Oral prednisone or equivalent may be used.

The dose is tailored to:

• Severity
• Body weight
• Systemic diagnosis

The taper should follow:

Clinical response rather than a fixed calendar schedule.

When Intravenous Steroid Is Considered

High-dose IV corticosteroid may be used for:

• Severe posterior scleritis
• Rapidly progressive necrotizing disease
• Sight-threatening inflammation

usually while systemic evaluation is underway.

Limits of Topical Steroid Therapy

Topical corticosteroids penetrate poorly into the sclera.

Therefore:

Topical steroid alone is usually inadequate for true scleritis.

They may still be useful for associated:

• Anterior uveitis
• Corneal inflammation

Local Steroid Injection

Modern practice is more nuanced than older teaching.

Subconjunctival/periocular corticosteroid may be considered in selected:

Noninfectious, nonnecrotizing anterior scleritis

but should generally be avoided in:

• Infectious disease
• Necrotizing disease
• Significant scleral thinning

When Long-Term Immunomodulation Is Needed

Steroid-sparing therapy should be considered when:

• Disease recurs
• Long-term steroid is required
• Steroid toxicity develops
• Necrotizing disease is present
• Systemic vasculitis exists

Common Steroid-Sparing Medications

Frequently used agents include:

• Methotrexate
• Mycophenolate mofetil
• Azathioprine

Choice depends on:

• Underlying systemic disease
• Comorbidities
• Severity
• Prior treatment response

Therapy for Severe Vasculitic Scleritis

Necrotizing disease associated with systemic vasculitis may require:

• Rituximab
• Cyclophosphamide

particularly in:

• GPA
• Severe systemic ANCA-associated disease

Management should be coordinated with:

• Rheumatology
• Internal medicine

Biologic Options for Refractory Disease

Biologic therapies may be used when conventional treatment fails.

Examples include:

• Infliximab
• Adalimumab
• Rituximab

Selection is guided by the underlying inflammatory disorder.

Treating an Infectious Cause

Infectious scleritis requires:

Organism-directed antimicrobial therapy

which may involve:

• Topical antibiotics
• Systemic antibiotics
• Antifungals
• Antivirals
• Surgical debridement

Steroid escalation should be avoided until infection has been adequately addressed.

Pseudomonas-Related Disease

Pseudomonas aeruginosa is a classic cause of aggressive infectious scleritis after:

• Pterygium surgery
• Scleral surgery
• Trauma

It may produce:

• Abscesses
• Necrosis
• Rapid scleral destruction

and often requires prolonged therapy.

Herpetic Scleritis

HSV and VZV may cause:

• Unilateral scleritis
• Keratitis
• Uveitis
• Reduced corneal sensation

A history of:

• Herpes zoster ophthalmicus
• Recurrent herpetic keratitis

may provide the clue.

Treatment generally includes:

Systemic antiviral therapy.

Protecting a Thinned Sclera

Patients with major scleral thinning should avoid:

• Eye rubbing
• Ocular trauma

Protective eyewear may be advisable when the structural integrity of the globe is compromised.

When Surgery Becomes Necessary

Surgery is rarely required but may be necessary for:

• Impending perforation
• Established perforation
• Severe scleral thinning
• Associated corneal melt

Reinforcing the Globe

A scleral or other tectonic patch graft may:

• Restore structural integrity
• Prevent perforation

However:

Surgery does not replace systemic control of active inflammation.

Signs That Treatment Is Working

Improvement is suggested by:

• Reduced pain
• Less tenderness
• Reduced vascular congestion
• Decreased scleral edema
• Stabilization of thinning
• Resolution of posterior fluid

Pain improvement is useful but cannot be relied upon alone, especially in:

Scleromalacia perforans.

Follow-Up Intensity

Review frequency depends on severity.

Severe, necrotizing, posterior, or infectious disease may require:

• Review within days
• Frequent reassessment during treatment changes

Stable cases can be followed less frequently.

Expected Disease Course

Recurrence is common.

Prognosis depends on:

• Scleritis subtype
• Presence of necrosis
• Posterior involvement
• Infectious etiology
• Associated systemic vasculitis
• Promptness of treatment

Diffuse and nodular anterior disease usually have:

Better visual outcomes than necrotizing disease.

Why Necrotizing Disease Is High Risk

Necrotizing scleritis is associated with:

• Severe ocular morbidity
• Systemic autoimmune vasculitis
• Risk of globe-threatening thinning

It should therefore be treated as both:

An ophthalmic and systemic urgency.

Possible Eye Complications

Important complications include:

• Scleral thinning
• Scleral perforation
• Peripheral ulcerative keratitis
• Anterior uveitis
• Cataract
• Secondary glaucoma
• Choroidal folds
• Exudative retinal detachment
• Macular edema
• Optic neuropathy
• Permanent visual loss

High-Yield Takeaways

• Scleritis is a deep, potentially sight-threatening inflammation of the sclera; necrosis is confined to the necrotizing subtypes.
• The principal forms are diffuse anterior, nodular anterior, necrotizing with inflammation, scleromalacia perforans, and posterior scleritis.
• The classic symptom is severe deep boring pain, often radiating to the brow or jaw and sometimes waking the patient from sleep.
• A violaceous hue, marked tenderness, and failure of deep vessels to blanch with phenylephrine favor scleritis over episcleritis.
• Scleromalacia perforans can be painless despite profound scleral thinning, especially in longstanding rheumatoid arthritis.
• Important systemic associations include rheumatoid arthritis, granulomatosis with polyangiitis, relapsing polychondritis, SLE, and other systemic vasculitides.
• Necrotizing disease should trigger urgent evaluation for ANCA-associated vasculitis.
• Always consider infectious scleritis before escalating immunosuppression, especially after surgery or trauma.
• Pseudomonas is a classic cause of severe postoperative infectious scleritis.
• Posterior scleritis may cause choroidal folds, optic disc edema, exudative retinal detachment, and painful visual loss.
• The classic B-scan finding is the T-sign, caused by fluid in the posterior sub-Tenon space.
• Mild noninfectious anterior disease may respond to oral NSAIDs.
• More severe, posterior, or refractory disease usually requires systemic corticosteroids.
• Chronic or recurrent disease often needs steroid-sparing immunomodulation, commonly methotrexate, mycophenolate, azathioprine, rituximab, or other agents tailored to the systemic disorder.
• Topical corticosteroid alone is usually inadequate for true scleritis.
• Local steroid injection may be considered only in carefully selected noninfectious, nonnecrotizing cases.
• Scleral patch grafting is reserved mainly for impending or actual perforation and must be combined with adequate control of the underlying inflammatory process.
• The major threats are scleral necrosis, perforation, peripheral ulcerative keratitis, glaucoma, posterior segment complications, and systemic vasculitis.