Episcleritis

Episcleritis is an inflammatory condition affecting the episcleral tissue that lies between the conjunctiva and the sclera.[7, 8] It usually is a mild and self-limiting but recurrent disease. Most cases are idiopathic, although up to one third have an underlying systemic condition. Some cases may be caused by exogenous inflammatory stimuli.[9, 10, 11]

The pathophysiology is poorly understood. The inflammatory response is localized to the superficial episcleral vascular network, and histopathology shows nongranulomatous inflammation with vascular dilatation and perivascular infiltration.

The two clinical types of episcleritis are diffuse and nodular/focal.

In diffuse episcleritis, the more common type, there are intermittent bouts of moderate-to-severe inflammation that often recur at 1- to 3-month intervals. The episodes usually last 7 to10 days, and most resolve after 2 to 3 weeks. Prolonged episodes may be more common in patients with associated systemic conditions. Some patients note that episodes are more common in the spring or fall. The precipitating factor is rarely found, but attacks have been associated with stress, allergy, trauma, and hormonal changes.

Patients with nodular/focal episcleritis have prolonged attacks of inflammation that are typically more painful than diffuse episcleritis. Many patients with nodular episcleritis have an associated systemic disease.[3]

Diffuse episcleritis (84% of cases) is more common than nodular scleritis (16% of cases), and the mean age of all patients with episcleritis is 47.4 years.[4] Unilateral inflammation is seen in two thirds of patients with episcleritis. Episcleritis is more common in females than in males, although the difference is not statistically significant.[4, 5]

The prognosis of episcleritis is favorable.[2]

Episcleritis is usually self-limited. The patient is usually comforted to know that it does not progress to a more serious disorder or result in loss of visual function.

All patients should undergo a thorough history, including a review of systems.

Many patients complain of acute onset of mild-to-moderate discomfort, although some may notice only an area of painless injection.

Photophobia and watery discharge may be noted.

The diagnosis of episcleritis is mainly based on clinical findings.

Slit-lamp examination reveals edema of the episcleral tissue and injection of superficial episcleral vessels.

The injection may be diffuse in diffuse episcleritis or localized and associated with a nodule in nodular episcleritis. The injection in episcleritis blanches with instillation of 10% phenylephrine ophthalmic drops, but not in scleritis.

Localized temporal inflammation in a patient with nodular episcleritis.

Other ocular findings that may be found in episcleritis include anterior uveitis and ocular hypertension.[4, 5]

Most cases are idiopathic; however, up to one third of cases may have an underlying systemic condition,[12, 13, 14] particularly connective tissue or vasculitic diseases.

Collagen-vascular diseases associated with episcleritis include the following:

• Rheumatoid arthritis
• Systemic lupus erythematosus
• Polyarteritis nodosa
• Seronegative spondyloarthropathies - Ankylosing spondylitis, inflammatory bowel disease, reactive arthritis, psoriatic arthritis
• Wegener granulomatosis
• Juvenile idiopathic arthritis

Other noninfectious conditions associated with episcleritis include HLA-B27 associated,[15] Behcet disease, and sarcoidosis.[16] Gout, atopy, and acne rosacea have also been associated with episcleritis.

Foreign bodies may cause episcleritis.

Episcleritis may also be associated with infectious causes, including the following:

• Bacteria, including tuberculosis, Lyme disease, syphilis, and cat-scratch disease
• Viruses, including herpes simplex and herpes zoster; Episcleritis can also be seen in patients with Covid-19. ^{[17, 18]}
• Fungi
• Parasites

Episcleritis was found to be complicated by anterior uveitis in 16% of cases based on a large study from a tertiary referral study. Other complications included ocular hypertension and cataract progression.[4] However, the latter two complications were seen only in patients with episcleritis based on a population-based study.[19]

All patients should undergo a thorough history, including a review of systems. Results of this review and findings from the physical examination are used to determine the need for specific laboratory studies. In most patients with mild self-limited disease, laboratory studies are not necessary.

Patients with nodular episcleritis or those with severe and recurrent/persistent diffuse episcleritis may require a limited workup, although the review of systems is unremarkable. Useful laboratory studies in this group of patients include serum uric acid, complete blood count with differential, antinuclear antibody, rheumatoid factor, erythrocyte sedimentation rate, Venereal Disease Research Laboratory (VDRL) test, fluorescent treponemal antibody absorption (FTA-ABS) test, and chest x-ray. Patients with a long history of low back pain or stiffness should be evaluated for ankylosing spondylitis.

Histologic findings include nongranulomatous inflammation with perivascular infiltrates and vascular dilatation.

Evaluations of the sclera and episclera using anterior segment optical coherence tomography (AS-OCT) have been shown useful in monitoring the effectiveness of therapy.[20] Differentiating scleritis from episcleritis can be helpful. The former demonstrates increased thickness of the sclera and intrascleral hyporeflective areas of edema on AS-OCT.[21]

More recently, a pilot study on the use of AS-OCT in conjunction with anterior segment OCT angiography (AS-OCTA) in differentiating patients with scleritis and episcleritis was conducted. Results show that both combined may be adjunctive tools by differentiating superficial from deep scleral inflammation by assessing the degree of vascularity and tissue thickness of the different tissue layers.[22]

Biopsy can be performed in atypical cases where the diagnosis is not clear. In rare cases, episcleritis can mimic a mass.[23]  On the other hand, malignancy can also present as episcleritis.[6]  

Episcleritis is a self-limited inflammation that generally causes little or no permanent damage to the eye. Many patients with episcleritis may not require any treatment.

Local therapy

Diffuse episcleritis often requires no treatment. Artificial tears are useful for patients with mild-to-moderate symptoms.[24] Patients with severe or prolonged episodes may require artificial tears and/or topical corticosteroids.

Nodular episcleritis is more indolent and may require local corticosteroid drops or anti-inflammatory agents.

Topical ophthalmic 0.5% prednisolone, 0.1% dexamethasone, loteprednol etabonate 0.5%, or 0.1% betamethasone daily may be used.

In a small series of patients at a tertiary referral center, about three quarters of patients with episcleritis responded to topical therapy alone.[5]

Systemic therapy

Systemic anti-inflammatory agents may be useful in eyes that are not responsive to topical therapy.

Systemic nonsteroidal anti-inflammatory drugs (NSAIDs) may be given until inflammation is suppressed. NSAIDs used in treatment of episcleritis include flurbiprofen (100 mg tid), indomethacin (100 mg daily initially and decreased to 75 mg daily), and naproxen (220 mg up to 6 times per day). Naproxen 500 mg is reserved for patients with more severe episcleritis.

The response to NSAIDs differs, and an NSAID that is effective in one patient may not be effective in another. These agents should be given with food in order to prevent gastrointestinal side effects.

Patients who do not respond or who have an incomplete response to both local therapy and systemic NSAIDs after 1 month may be treated with oral corticosteroids for at least 1 month in a tapering dose.[5] About 20% of patients with nodular episcleritis require oral corticosteroid treatment.[19]

Patients with episcleritis secondary to infectious causes need appropriate antibiotic therapy.

Sunglasses may be useful for patients with sensitivity to light.

Patients should watch for the appearance of new systemic symptoms and should be advised to seek medical attention to rule out a systemic disease.

Long-term continuous therapy with steroid preparations should be avoided because of the danger of inducing cataract, glaucoma, and systemic complications. Moreover, excessive steroid use in episcleritis may increase the risk of recurrence.

The goals of pharmacotherapy are to decrease pain, improve quality of life, to reduce morbidity, and to prevent complications.[25]

Class Summary

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Dexamethasone ophthalmic (Maxidex)

Suppresses the inflammatory response to a variety of agents and probably delays healing. Used for steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe; when the inherent hazard of steroid use is accepted. Duration of treatment will vary from a few days to several weeks, according to therapeutic response.

Prednisolone acetate 1% (Pred Forte, Omnipred, Pred Mild)

Sterile ophthalmic suspension that is a topical anti-inflammatory agent for treating steroid responsive inflammation of palpebral and bulbar conjunctiva as well as cornea and anterior segment. Shake well prior to use. Do not discontinue therapy prematurely.

Loteprednol ophthalmic (Alrex, Lotemax, Inveltys, Eysuvis)

Sterile ophthalmic suspension with an ester steroid. This molecular change from the basic steroid ring structure substitutes an ester rather than a ketone at the 20 position, thus imparting a favorable IOP and cataractogenesis profile. It is available as a suspension in 0.2%, 0.25%, 0.5%, and 1% concentrations.

Class Summary

Their mechanism of action is not known but may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Flurbiprofen

May inhibit cyclooxygenase enzyme, which, in turn, inhibits prostaglandin biosynthesis. These effects may result in analgesic, antipyretic, and anti-inflammatory activities. Available in 50- and 100-mg doses.

Indomethacin (Indocin, Tivorbex)

Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation; inhibits prostaglandin synthesis. For use with episcleritis that has been nonresponsive to topical treatment.

Ibuprofen (Advil, Motrin, Addaprin, Dyspel, Provil)

Ibuprofen is usually the DOC for treating mild to moderate pain if no contraindications exist. It is one of the few NSAIDs indicated for fever reduction.

Ketoprofen

Ketoprofen is used for relief of mild to moderate pain and inflammation. Small dosages are indicated initially in small patients, elderly patients, and patients with renal or liver disease. Doses higher than 75 mg do not increase the therapeutic effects. Administer high doses with caution and closely observe the patient’s response.

Naproxen (Aleve, Anaprox, Anaprox DS, Naprelan, Naprosyn)

Naproxen is used for the relief of mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing COX activity, which results in decreased prostaglandin synthesis.