Skleritis

01Pathophysiology

Scleritis is a granulomatous or necrotizing inflammatory process involving the full thickness of the sclera. The sclera is composed of dense, relatively avascular collagen (types I and III), which means that once inflammation takes hold, the tissue is poorly equipped to contain or resolve the damage on its own.

The underlying mechanism in most cases is an immune complex-mediated vasculitis affecting the deep episcleral and scleral vessels. Activated T-cells and macrophages infiltrate the scleral stroma, releasing pro-inflammatory cytokines (TNF-alpha, IL-1) and matrix metalloproteinases. This cascade causes fibrinoid necrosis of the vessel walls and surrounding collagen destruction. The deep vascular involvement is why the pain is so severe and why it radiates along branches of the trigeminal nerve (V1): the sclera shares sensory innervation with the periorbital structures. This also explains why the pain worsens with eye movement, because the extraocular muscle insertions tug directly on inflamed scleral tissue.

In necrotizing scleritis, the destructive process is more aggressive and leads to scleral thinning. As the sclera thins, the underlying uveal pigment shows through, producing the characteristic blue-grey or dark patch on examination. If thinning progresses, the eye is at risk for scleral perforation (globe rupture), which constitutes an ophthalmic emergency.

A key clinical teaching point: approximately 50% of patients with scleritis have an underlying systemic autoimmune condition, most commonly rheumatoid arthritis. Necrotizing scleritis in a patient with longstanding rheumatoid arthritis is strongly associated with active systemic vasculitis and carries increased mortality if the systemic disease is left untreated. This is why a new diagnosis of scleritis should always prompt a systemic workup.

02Classification and Clinical Manifestations

Classification of Scleritis (Watson and Hayreh)

Scleritis vs. Episcleritis Comparison

This is a high-yield comparison that appears repeatedly on examinations. The two conditions are often placed side-by-side in vignettes, and the distinguishing features are very testable.

The phenylephrine blanching test is the single most tested discriminator. If the redness blanches with topical phenylephrine, the inflamed vessels are superficial (episcleritis). If it does not blanch, the inflammation involves the deep scleral vessels (scleritis).

03Diagnostic Workup

Scleritis is primarily a clinical diagnosis. The workup begins at the slit lamp, where the examiner identifies deep scleral vessel engorgement that is distinct from the more superficial, mobile, and bright-red episcleral injection. Instillation of phenylephrine 2.5% is the key bedside maneuver: failure to blanch confirms deep vessel involvement.

When posterior scleritis is suspected (pain on movement, decreased vision, no visible anterior inflammation), B-scan ultrasonography is the most valuable confirmatory study. The classic finding is the "T-sign", which represents thickening of the posterior scleral wall with fluid tracking into the sub-Tenon space around the optic nerve.

Because of the strong systemic disease association, every new diagnosis of scleritis warrants a laboratory evaluation for autoimmune conditions. The panel typically includes ESR, CRP, rheumatoid factor, anti-CCP antibodies, c-ANCA and p-ANCA (to evaluate for granulomatosis with polyangiitis), ANA, and a urinalysis to screen for renal involvement. This workup is not just academic: identifying an underlying systemic vasculitis changes the management and prognosis fundamentally.

04Management and Treatment

The management of scleritis follows a stepwise escalation model. The first-line treatment for non-necrotizing anterior scleritis is oral NSAIDs. Topical drops alone are insufficient because the sclera is too thick and avascular for topical agents to penetrate meaningfully. This is a critical distinction from episcleritis, where topical therapy works well.

If oral NSAIDs fail to control symptoms within 2-3 weeks, the next step is systemic corticosteroids. Prednisone is started at 1 mg/kg/day and maintained until inflammation is controlled, then tapered gradually to avoid rebound. Patients on prolonged corticosteroids require monitoring for hyperglycemia, osteoporosis, and adrenal suppression.

Necrotizing scleritis is treated as a rheumatologic emergency. These patients typically require immunosuppressive agents from the outset, often in coordination with rheumatology. Cyclophosphamide is the traditional choice for GPA-associated necrotizing scleritis, while methotrexate or mycophenolate may be used for less aggressive autoimmune etiologies. Rituximab (anti-CD20 monoclonal antibody) has emerged as an effective option for refractory cases.

A teaching pearl: never use topical steroids as monotherapy for scleritis. They do not reach the deep scleral inflammation and may mask symptoms while disease progresses. Also, subconjunctival corticosteroid injections are contraindicated in necrotizing scleritis because they can precipitate scleral perforation in already thinned tissue.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students miss scleritis questions is by confusing it with episcleritis. The vignette will describe a red eye with some discomfort, and the student defaults to the more benign diagnosis. The key is to look for severity markers: deep boring pain, sleep disruption, radiation to the forehead or jaw, and a violaceous hue. If the stem mentions that phenylephrine did not blanch the redness, scleritis is confirmed.

A second trap involves posterior scleritis. Because it presents with decreased vision, pain on movement, and sometimes disc edema or exudative retinal detachment, students may jump to diagnoses like optic neuritis, orbital cellulitis, or choroidal melanoma. The giveaway is the B-scan showing diffuse posterior scleral thickening with the T-sign, combined with an autoimmune history.

Third, students sometimes select topical corticosteroids as treatment. This is always wrong for scleritis. The inflammation is too deep for topical penetration, and systemic therapy is mandatory.

Finally, remember the systemic connection: a question that presents new-onset scleritis in a middle-aged woman with joint deformities is testing whether you will order a rheumatologic workup. Necrotizing scleritis in a patient with rheumatoid arthritis is an indicator of active systemic vasculitis and demands immunosuppressive therapy, not just eye-focused treatment. The core competency being tested is the ability to recognize scleritis as a systemic disease with ocular manifestation, not merely an eye problem.