Scleritis

Etiology

Scleritis can be idiopathic or caused by infectious or noninfectious conditions. Additionally, associations with malignancy, autoimmune diseases, and surgically induced or medication side effects are causative factors. Viruses, bacteria, fungi, and parasites can cause infectious scleritis and are reported to occur in 4% to 10% of all cases.[2] Choroidal melanomas and conjunctival tumors can create ocular inflammation that can mimic the signs and symptoms of scleritis. 50% of patients with scleritis will have an autoimmune condition, sometimes undiagnosed at the time of presentation. Rheumatoid arthritis and systemic vasculitic conditions are most commonly associated with scleritis. [3]

Surgically induced scleritis has been associated with pterygium removal and scleral buckle procedures. Medications used to treat osteoporosis such as bisphosphonates have been found to cause scleritis; however, reports of this occurrence are rare.[2]

Epidemiology

Limited, population-based studies have reported 10,500 cases of scleritis in the United States per year or an estimated four to six cases per 100,000 persons.[3]

It affects patients in middle age, commonly between 47 to 60 years.[2] Scleritis is more common in women, with a 60% to 74% predominance.[2] Limited information is known about the incidence of children besides case reports.

Pathophysiology

The exact pathophysiology of scleritis is still under investigation. The anatomical structure of the sclera includes an extracellular matrix of collagen, elastin, and proteoglycans that closely resemble the components of joints, causing it to be susceptible to inflammatory conditions such as rheumatoid arthritis.[1] Additionally, the sclera is mostly avascular and requires the transport of nutrients and the removal of cellular wastes on the surrounding episcleral and choroidal vascular systems.

Histopathology

The disease's histopathological features are similar to those seen in vasculitic conditions. Scleral biopsies from patients with severe scleritis or necrotizing scleritis demonstrated vascular occlusions and infiltration, necrosis, and evidence of macrophages and T cells.[3]

History and Physical

The presentation can vary depending on the location and subtype of scleritis and can be unilateral or bilateral.[4] [5]

Anterior

• Anterior from the rectus muscle's limbus-insertion
• Occurs in 98% of cases
• Mild to moderate pain and tenderness; worse at night
• Pain with eye movement
• A blue-violet hue of deep vessels; best seen in daylight or natural illumination
• Photophobia, tearing, and possibly decreased vision
• No vessel blanching with the installation of 2.5% topical phenylephrine

Diffuse

• Most common (45% to 61%)
• Extensive scleral edema; congestion of deep and superficial vessels
• Can be localized or encompass the entire anterior sclera

Nodular

• Multiple, well-defined, and non-moveable nodules
• Scleral edema and congestion of vessels
• Usually more localized

Necrotizing

• With inflammation – intense congestion of vessels
• Severe pain
• Most severe form with the worst prognosis
• Highest association with a systemic disease
• Scleral thinning and exposure of choroid possible
• Inflammation can spread to other ocular tissues such as the cornea, ciliary body, or trabecular meshwork

Necrotizing Without inflammation (Scleromalacia perforans)

• Severe scleral thinning- with visible choroid
• Can be asymptomatic or can have reduced acuity resulting from corneal astigmatism caused by the scleral thinning 

Posterior

• Behind the insertion of the rectus muscles
• Occurs in 2% of cases
• Can occur in conjunction with anterior scleritis  
• May present with decreased vision, with or without ocular pain
• Retinal detachments, optic nerve swelling, and cotton wools spots can be seen on dilated examination
• Diffuse or nodular subtypes can be differentiated with B-scan, CT), or MRI
• B-scan ultrasound displays thickening of the posterior sclera (greater than 2millimeters); retrobulbar thickening and fluid surrounding the optic nerve create a characteristic “T” sign
• Diffuse - Diffuse thickening of sclera and choroid
• Nodular- Scleral nodules seen on B-scan

Evaluation

The diagnosis is based on the clinical presentation and ocular exam with a detailed history and review of systems, targeted laboratory tests, and imaging studies.[2]

Common Lab Tests

• Antineutrophil cytoplasmic antibodies (ANCAs) – specific for granulomatosis with polyangiitis (Wegener granulomatosis)
• Antinuclear Antibodies (ANA) – suggestive of systemic lupus erythematosus and other autoimmune conditions 
• Complete blood count(CBC) with differential – identify infectious or inflammatory processes
• C-reactive protein – elevated in inflammatory conditions
• ESR – suggestive of giant cell arteritis, inflammatory or infectious processes
• HLA-B27 -  more useful in cases of uveitis; rare association with scleritis
• Lyme serology – rule out Lyme Disease, presents with recurrent diffuse anterior scleritis
• Rheumatoid factor – suspect for rheumatoid arthritis
• Angiotensin-converting enzyme (ACE) -  suggestive of sarcoidosis
• Serum lysozyme – suggestive of sarcoidosis
• Rapid plasma reagin (RPR) – suggestive for syphilis
• Fluorescent treponemal antibody absorption test (FTA-ABS) – suggestive for syphilis 

Imaging

• Chest X-Ray – rule out sarcoidosis
• B-scan – assess for posterior scleritis
• MRI – can be used if B-scan is non-conclusive
• CT – can be used if MRI is non-indicated (posterior scleritis)
• Ultrasound biomicroscopy (UBM) – can be used to differentiate episcleritis from scleritis
• Optical coherence tomography (OCT) – can display thickened sclera on anterior segment OCT and thickened choroidal tissue
• Anterior segment fluorescein and indocyanine green angiography (ICGA) – useful in visualizing necrosis

Treatment / Management

The treatment and management of scleritis are designed to determine any causative factor, manage ocular inflammation, control ocular pain and symptoms, prevent sequela, and reduce recurrences.[2][4] [5](B3)

Anterior Infectious

Treatment tailored to the infectious cause

Anterior Noninfectious

First-line treatments

• Topical corticosteroid eyedrops
  • Can be used in mild cases; some report very limited success
  • Prednisolone acetate 1.0% or difluprednate 0.05% four times per day are options
• Oral NSAIDs
  • Can start with one agent and switch to another agent if not effective
  • Indomethacin, commonly used, 50 mg, 3 times per day
  • Ibuprofen 600 mg, 3 times per day
  • Naproxen 500 mg, 2 times per day 

Second-line treatments

• Oral corticosteroids
  • Prescribed when oral NSAID treatment fails
  • Oral prednisone 1 mg/kg/day; 60 to 80 mg per day
  • Dose continued until one month after the resolution of scleritis, then tapered accordingly

• Subconjunctival corticosteroid injection
  • Can be used when steroids are contraindicated
  • Controversial use with previous studies of scleral necrosis/perforation
  • More recent reports have indicated improved safety and efficacy of injections

    Third line treatments

• Immunosuppressive agents (steroid-sparing)
  • Reserved for more severe cases of scleritis, with oral steroid treatment failure or concern for side effects with long-term oral steroid use
  • Methotrexate is the most commonly prescribed agent; starting dose of 0.15 mg/kg per week in combination with folic acid supplements
  • Other agents include azathioprine, mycophenolate, and cyclophosphamide

    Fourth line treatments

• Biologics
  • Ongoing research with the use of biologics such as infliximab and rituximab has been shown to have a positive treatment response  

Posterior 

Requiring intense and immediate treatment

    First-line treatments

• Oral NSAIDs
  • Commonly used: indomethacin, naproxen, ibuprofen

    Second-line treatments

• Oral corticosteroids

            - Prescribed when oral NSAID treatment fails

            - Oral prednisone of 1 mg/kg/day; 60 to 80 mg per day

    Third line treatments

• Immunosuppressive/antimetabolites agents
  • Reserved for severe cases of scleritis and with high dose oral steroid treatment failure after 1 month
  • Commonly prescribed agents include methotrexate, azathioprine, and mycophenolate 

    Fourth line treatments

• Biologics
  • Infliximab and rituximab

Differential Diagnosis

The main differential diagnosis of scleritis is episcleritis. Episcleritis is defined as inflammation of the superficial episcleral tissues and blood vessels. Patients can present with mild pain, redness, foreign body sensation, and tearing. Upon installation of 2.5% topical phenylephrine in the affected eye, the blood vessels will blanch with episcleritis but will not blanch with scleritis.[2] Episcleritis is usually idiopathic and resolves without treatment.  

Prognosis

Visual prognosis is relatively good for patients with mild or moderate scleritis that respond well to the appropriate medical treatment and management of any underlying systemic condition.[6] Necrotizing and posterior scleritis cases pose a higher risk of visual loss to the extent of the inflammation and involvement of other ocular structures.

Complications

Sequela resulting from scleritis can vary depending on the severity of presentation and any associated autoimmune conditions and can include decreased vision, cataracts, increased intraocular pressure, scleral thinning or melting, and corneal thinning. [6]