Scleritis in Emergency Medicine

Proposed mechanisms for noninfectious scleritis include a variety of immune system effects, both cell-mediated and humoral, antibody mediated. Antigenic stimuli probably occur, and matrix metalloproteinases appear to be involved in the destruction of scleral tissue.[10]

The sclera, which consists of collagen and elastic connective tissue, provides a tough protective casing around the eye. Enzymatic degradation of collagen fibrils and invasion of inflammatory cells, including T cells and macrophages, appear to play an important role.

The thickness of the sclera varies from 0.3-1.2 mm. Healthy sclera is consistently white. Inflammation, the principal pathology affecting the sclera, is frequently part of a general inflammatory reaction associated with a systemic immune-mediated collagen vascular disease.[11, 12, 13]

Inflammation of the sclera can progress to ischemia and necrosis, eventually leading to scleral thinning and perforation of the globe. Necrotizing anterior scleritis represents a particularly destructive form of scleritis.

Scleritis coexists with a serious systemic disease in almost one half of cases; the underlying problem is frequently a connective tissue disorder.[12] Rheumatoid arthritis (RA) is the underlying disease for approximately one sixth of patients suffering from scleritis, and approximately 1% of patients with RA will develop scleritis at some point in the course of the disease. Scleritis associated with RA is due to the development of a rheumatoid nodule on the sclera and is associated with an increased risk of mortality.[12]

Other connective tissue and autoimmune diseases seen with scleritis include the following:[12]

• Systemic lupus erythematosus (SLE)
• Polyarteritis nodosa
• Seronegative spondyloarthropathies - Ankylosing spondylitis, psoriatic arthritis, reactive arthritis
• Granulomatosis with polyangiitis (Wegener granulomatosis)
• Relapsing polychondritis ^[14]
• Sarcoidosis
• Inflammatory bowel disease
• Sjögren syndrome
• IgG4-related disease ^[15]

Additional causes of scleritis include the following:

• Syphilis ^[16]
• Post–herpes zoster ophthalmicus
• Poststreptococcal syndrome ^[17]
• Tuberculosis
• Gout
• Lyme disease
• Foreign body
• Hypertension

Surgically-induced scleritis is a rare complication following ophthalmologic procedures such as the following:

• Cataract surgery
• Pterygium excision
• Strabismus surgery
• Retinal detachment repair ^[18]
• Intravitreal injection ^[19]

Scleritis is an uncommon disease. Well-defined incidence rates are hard to find. An epidemiologic study of northern California data concluded that the overall incidence of scleritis was 3.4 per 100,000 person-years and the annual prevalence was 5.2 per 100,000 persons.[20] A population-based study from Olmsted County, Minnesota found that the annual incidence rate of scleritis was 5.54 per 100,000. The mean age at diagnosis was 48.8 years.[21]

Of patients diagnosed with scleritis, anterior scleritis is demonstrated in 94% of patients, as opposed to posterior scleritis, which is diagnosed only 6% of the time. An increased incidence of scleritis has been reported in patients taking bisphosphonates, which are commonly used in the management of osteoporosis.[18]

As scleritis is associated with systemic autoimmune diseases, it is more common in women, however, men are more likely to have infectious scleritis than women.[22]  Cases have been reported in patients ranging from 11-87 years of age but it usually occurs in the fourth to sixth decades of life. Mean age for all types of scleritis is 52 years.

Necrotizing scleritis, the most destructive type of scleritis, and scleritis with extensive scleral thinning or perforation convey less favorable prognoses than other types of scleritis. Prognosis of scleritis, when originating from systemic disorders, usually conforms to the course of the underlying disease. 

Morbidity arises from primary scleritis and associated systemic disease. In 15% of cases, scleritis is the presenting manifestation of collagen vascular disorder and may precede additional symptoms by one to several months. A significant percentage of patients with concurrent scleritis and collagen vascular disease die within 5 years.

One study demonstrated that spectral domain optical coherence tomography may be useful in following up on patient response to treatment.[23]

Scleral thinning leading to global perforation is the most devastating complication. Giant pigment epithelial tear and retinal detachment has been reported in a patient with scleritis.[24]  

Visual impairment is a possible complication. The cornea is affected more than 50% of time. Damage to the cornea may include uveitis, keratitis, glaucoma, and cataracts.[25]  Posterior chamber derangements may include the following:

• Optic neuritis
• Choroidal detachment
• Macular edema
• Retinal hemorrhage and/or detachment
• Papilledema

Scleritis is subacute; with a more gradual onset than in episcleritis.[26]  Scleritis generally persists from months to years, whereas episcleritis usually resolves within weeks. Both eyes are affected in slightly more than one half of cases.

Severe, constant, deep, boring, or pulsating pain is noted. Pain worsens with movement of the eye and is worse at night and may awaken the patient. Pain may be referred to the eyebrow, temple, or jaw. Occasionally, the configuration of the pain pattern corresponds to the course of the trigeminal nerve.

Erythema of the eye is a defining symptom with anterior scleritis. Other signs and symptoms include lacrimation and photophobia. Discharge is ordinarily not part of the clinical picture of scleritis. Less common manifestations include nausea/vomiting and headache

Prior history may include underlying systemic disease[12] , trauma, ocular surgery, glaucoma, exposure to irritants/chemicals, previous use of eye drops and medications. Uncommonly, patients may report similar previous episodes.

 

As with any eye complaint (except chemical injury), begin with vision testing. Visual acuity may be normal or decreased with all forms of scleritis. Visual impairment is most pronounced with posterior scleritis.[27]

Additionally, a complete physical examination, particularly of the skin, joints, heart, and lungs, may be obligatory when an underlying complicating illness is suspected.

For the eye examination, ensure satisfactory lighting. Inspect for breadth and degree of injection, as well as the presence of a bluish hue signifying attenuation of the sclera. Prominent findings may include photophobia, tearing without discharge, tenderness of the eye, and purplish red, edematous, engorged blood vessels. Deeper sclera blood vessels appear darker, follow a radial pattern, and do not move when manipulated with a cotton swab. Administration of topical phenylephrine 2.5-10% causes blanching of the more superficial episcleral vessels but does not change the engorgement of deeper sclera vessels and can help differentiate between scleritis and episcleritis.

Infectious scleritis should be suspected in patients with a history of eye trauma or surgery. Eye examination findings in infectious cases include mucopurulent exudate, scleral ulcers, or scleral abscesses.[28]

Perform a slit lamp/biomicroscopic examination to judge the depth and breadth of involvement. Determine whether there is diffuse or segmental involvement. Widespread injection of the conjunctival and deep scleral vessels is characteristic of diffuse anterior scleritis. Localized elevation of the sclera is representative of nodular anterior scleritis.

Nodules in anterior scleritis are immobile, differing from the non-mobile nodules that can be seen in episcleritis. Scleral thinning is suggested when the choroid pigment becomes a blue-violet hue best seen in natural lighting. Global perforation typically results in an abnormal shape of the pupil and/or uveal or vitreous prolapse. Use of a red-free filter (green light) helps identify avascular areas of the sclera. Corneal changes are present in up to 50% of cases. Examination of the eyelids for possible blepharitis or conjunctivitis should be performed.

Assess the anterior chamber for possible narrowing, hyphema, or hypopyon. Angle narrowing can be seen in acute angle-closure glaucoma. Hyphema can be seen with trauma and/or bleeding disorders. Hypopyon may be seen in uveitis/iritis.

External findings associated with posterior scleritis include restriction of eye movements, sensitivity to palpation, and proptosis. Dilation of the fundus may be necessary to identify posterior scleritis. Posterior scleritis may simulate amelanotic choroidal melanoma. Funduscopic examination of the patient with posterior scleritis may also reveal papilledema, choroidal folds, and retinal hemorrhage or detachment.[24]

The emergency department (ED) is the ideal location to initiate evaluation for collagen vascular disease, infection (conjunctival cultures), and immunocompetency. If scleritis is suspected, the emergency physician will contact an ophthalmologist. This would be a good opportunity to establish an evaluation and intervention plan. Getting the laboratory studies in the ED will save time for the patient and practitioners.

The diagnosis of scleritis is clinical. However, laboratory testing is often necessary to discover any associated connective tissue and autoimmune disease. Depending on the clinical suspicion, laboratory tests include, but are not limited to, the following:

• Complete blood count (CBC) and electrolytes
• Erythrocyte sedimentation rate (ESR)
• Syphilis testing
• Serum uric acid
• Rheumatoid factor
• Antinuclear antibody (ANA)

 

B-scan ultrasonography may assist in detecting posterior scleritis. Ultrasonographic changes include scleral and choroidal thickening, scleral nodules, distended optic nerve sheath, fluid in Tenons capsule, or retinal detachment.[22]  

MRI or CT scans may play a role, but they should be ordered in consultation with an ophthalmologist. Chest radiography may be indicated to look for underlying pulmonary involvement arising from systemic disease. Imaging of sacroiliac joints is prudent when ankylosing spondylitis is suspected.

Instillation of phenylephrine, a mydriatic vasoconstrictor, helps differentiate deep scleral episcleral blood vessel involvement from superficial involvement; superficial vessels blanch following application of phenylephrine, while deeper vessels remain unaffected.

The Seidel test helps detect possible global perforation. Apply a moistened fluorescein strip over the entire surface of the eye while viewing under a slit lamp. If perforation exists, the fluorescein dye becomes diluted by the aqueous humor, appearing as a green dilute stream within the dark, concentrated, orange dye. Alternatively, a Wood lamp may be used if a slit lamp is not available.

A primary complaint of atraumatic eye pain rarely necessitates prehospital care, other than expedient transport to the emergency department (ED). Take care not to overlook serious comorbidity. If global perforation is suspected, shield the eye and avoid palpation.

It is important to differentiate infectious scleritis from noninfectious scleritis, because corticosteroids or immunosuppressive agents are contraindicated in active infection. Patients with infectious scleritis should be treated with appropriate and specific antimicrobial therapy.[22, 28]

Recognition of the problem and timely ophthalmology referral are cornerstones of ED management. Severity of scleritis and depth of involvement determine the urgency of ophthalmology consultation.[5]  Serious systemic illness and initiation of immunosuppressive therapy may require coordination with an internist and/or rheumatologist.

Therapeutic goals for scleritis are to relieve the patient’s pain and initiate therapy that will positively alter the course of the disease.[31] From the patient's perspective, pain cessation may be the most important action taken by the emergency practitioner. Outcome in cases of noninfectious scleritis will depend on the patient's response to immunosuppressive therapy.[32]

Narcotics and systemic nonsteroidal anti-inflammatory drugs (NSAIDs) may render temporary pain relief and can be started in the ED. A variety of NSAIDs is available to choose from, including diflunisal, naproxen, indomethacin, piroxicam, sulindac, and ibuprofen. These are particularly effective in nodular and diffuse scleritis and ordinarily are prescribed for at least 1 week.

Detection of scleral thinning mandates application of an eye shield to the involved eye to decrease risk of perforation. Ensure that the eye guard does not contact the eyelid or globe. Apply tape from the forehead to zygoma. If an eye shield is not available, use a paper or polystyrene cup, provided it is large enough to cover the eye without placing undue pressure on the globe.

Scleritis treatment will require immunomodulator therapy once the definitive diagnosis is made. High-dose oral prednisone is used primarily in necrotizing scleritis and severe nonnecrotizing scleritis. Immunosuppressives are used as an adjunct when steroids alone fail to control progression of the disease and include cyclosporine, azathioprine, cyclophosphamide, and methotrexate. Increasing evidence supports a role for rituximab in refractory disease.[15] These drugs have serious side effects and contraindications and should be prescribed only by a physician who is well aware of their actions.

The emergency practitioner can discuss using a topical steroid agent with the ophthalmologist.[33] Although topical steroid therapy typically fails, it could be considered as first-line treatment for nonnecrotizing anterior scleritis, especially in cases in which the likelihood of complications from systemic steroid or NSAID therapy is high.[33]

Inpatient care rarely is indicated for scleritis, unless complicated by serious exacerbation of underlying disorder. Surgical management is generally not required except in rare cases of necrotizing scleritis.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are generally found to be effective in approximately one third of patients with diffuse anterior scleritis and two thirds of patients with nodular anterior scleritis.[34, 35] NSAIDs have also been found to be helpful in patients with idiopathic posterior scleritis.

Topical steroids (eg, prednisolone acetate 1.0%) can be used in mild cases.[1]  They have a high failure rate but should be discussed with the practitioner who will provide follow-up care.[33]

Systemic steroids are second-line treatments prescribed when NSAIDs fail. In noninfectious scleritis, methotrexate appears to be effective as a steroid-sparing agent and for providing long-term control of inflammation.[36] Similarly, rituximab has been found effective for noninfectious scleritis in case reports, a few small case series, and a randomized trial.[37]

Subconjunctival steroid injections for non-necrotizing scleritis remain controversial. Localized steroid injections may lead to increased intraocular pressure, scleral melting, or globe perforation/scleral rupture.

 

Class Summary

These agents are used to decrease pain and inflammation. NSAIDs are thought to act by inhibiting prostaglandin synthesis, interfering with migration of leukocytes, and inhibiting phosphodiesterase.

Indomethacin (Indocin)

Often considered the DOC. Indomethacin is rapidly absorbed. Metabolism occurs in the liver by demethylation, deacetylation, and glucuronide conjugation.

Diflunisal (Dolobid)

Nonsteroidal salicylic acid derivative that acts peripherally as an analgesic. Has antipyretic and anti-inflammatory effects; however, differs chemically from aspirin and is not metabolized to salicylic acid. It is a prostaglandin-synthetase inhibitor.

Naproxen (Naprelan, Anaprox, Aleve, Naprosyn)

Used for relief of mild-to-moderate pain. It inhibits inflammatory reactions and pain by decreasing the activity of the enzyme cyclooxygenase, resulting in a decrease of prostaglandin synthesis.

Naproxen is rapidly absorbed and has a half-life of 12-15 h. It is highly protein bound.

Ibuprofen (Motrin, Ibuprin, Advil)

Usually the DOC for treatment of mild- to- moderate pain, if no contraindications exist. Inhibits inflammatory reactions and pain, probably by decreasing activity of the enzyme cyclooxygenase, which results in prostaglandin synthesis.

Highly protein-bound drug that is readily absorbed orally. The half-life is short (1.8-2.6 h).

Sulindac (Clinoril)

Decreases activity of cyclooxygenase and, in turn, inhibits prostaglandin synthesis. Results in a decreased formation of inflammatory mediators.

Piroxicam (Feldene)

Chemically different from other NSAIDs. Extensively bound to plasma proteins. Decreases activity of cyclooxygenase and, in turn, inhibits prostaglandin synthesis. These effects decrease formation of inflammatory mediators.

Class Summary

These agents are used in severe (necrotizing scleritis) and resistant forms of the disease. Only an ophthalmologist experienced with the medication should prescribe these drugs.

Methotrexate (Folex, Rheumatex)

Mechanism of action in treatment of inflammatory reactions is unknown. May affect immune function and usually ameliorates symptoms of inflammation (eg, pain, swelling, stiffness).

Cyclophosphamide (Cytoxan, Neosar)

Chemically related to nitrogen mustards. As it is an alkylating agent, mechanism of action of active metabolites may involve cross-linking of the DNA, which may interfere with growth of normal and neoplastic cells.

Azathioprine (Imuran)

Inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting synthesis of DNA, RNA, and proteins.

Cyclosporine (Sandimmune, Neoral)

Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions, such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease for a variety of organs.

For children and adults, dosing should be based on ideal body weight.

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli and are useful in the treatment of recurrent scleritis.

Methylprednisolone (Depo-Medrol, Solu-Medrol, Medrol)

Administered IM or IV. Usually used in addition with other immunosuppressive agents.

Prednisone (Deltasone, Orasone, Sterapred)

Used to treat inflammatory and allergic reactions. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation.

Class Summary

Ocular corticosteroids, anti-inflammatory agents; bacterial and viral infections require concomitant antibacterial and antiviral coverage, respectively

Prednisolone ophthalmic (Econopred Plus, Inflamase Forte, Inflamase Mild)

Dosage for ophthalmic inflammatory conditions is 1-2 gtt of 1% solution BID-QID (may be more frequent during initial 24-48 hr).

Rituximab (Rituximab-arrx, Riabni, Rituxan)

Rituximab is a humanized monoclonal antibody that binds to CD20 antigen. It is approved for use in rheumatoid arthritis and granulomatosis with polyangiitis—autoimmune diseases associated with scleritis—and has demonstrated efficacy in treatment of refractory scleritis in patients with those diseases, as well as cases associated with other autoimmune disorders and idiopathic cases.