Episcleritis

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Practice Essentials

Episcleritis is an acute inflammation of the episclera that can affect one or both eyes.[1] Although it frequently is of unknown cause, around 26% to 36% of cases can be linked to underlying systemic conditions such as rheumatoid arthritis, ulcerative colitis, psoriatic arthritis, or systemic lupus erythematosus. Less commonly, infections such as Lyme disease and syphilis may also be associated with episcleritis.[2]

Episcleritis is self-limited and the prognosis is good.[3]

Patients may experience redness and mild ocular discomfort or pain; visual acuity is normal. Discharge and photophobia are rare.[2]

The two clinical types of episcleritis are diffuse and nodular or focal (nodular/focal). Patients with diffuse episcleritis, the more common type, experience intermittent episodes of moderate-to-severe inflammation that recur as often as every 1 to 3 months.

Patients with nodular/focal episcleritis have longer, more painful episodes, and they often have an associated systemic disease.[4]

Diagnosis

Episcleritis is diagnosed primarily on the basis of clinical findings. Slit-lamp examination shows edema of the episcleral tissue and injection of superficial episcleral vessels.[5, 6]

Clinicians should be alert to the possibility of malignancy or scleritis in these patients. Episcleritis can be the presenting sign of conjunctival lymphoma.[7]  Scleritis is considerably less common than episcleritis, but more commonly is linked to connective tissue or vasculitis diseases and the development of ocular complications.

All patients require a thorough history, including a review of symptoms, and a physical examination. Results from these will establish the need for specific laboratory studies, which may be unnecessary in most patients with mild self-limited disease.

In certain patients with severe disease, the following laboratory studies may be useful:

Evaluate patients with a long history of low back pain or stiffness for ankylosing spondylitis.

Treatment

Artificial tears are helpful for patients with mild-to-moderate symptoms, and those with severe or prolonged episodes may need artificial tears and/or topical corticosteroids. Patients with nodular episcleritis may need local corticosteroid drops or anti-inflammatory agents.[6]

Systemic anti-inflammatory agents may be helpful in eyes that are unresponsive to topical therapy.

Systemic nonsteroidal anti-inflammatory drugs (NSAIDs) that may be given until inflammation is suppressed 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.

Patients who fail to respond or who have an incomplete response to both local therapy and systemic NSAIDs after 1 month may be treated with oral corticosteroids for a month or longer in a tapering dose.[6]

Those with episcleritis resulting from infection require appropriate antibiotic therapy.

Patient education, follow-up

Patients with photosensitivity may benefit from sunglasses.

Patients should be instructed to watch for the appearance of new systemic symptoms and should seek medical care to rule out a systemic disease if such symptoms occur.

Avoid long-term continuous treatment with steroid preparations because of the risk of causing cataract, glaucoma, and systemic complications. Excessive steroid use in these patients may increase the risk for recurrence.

Background

Episcleritis is an inflammatory condition affecting the episcleral tissue that lies between the conjunctiva and the sclera.[8, 9] 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.[10, 11, 12, 1]

Pathophysiology

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.[4]

Epidemiology

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.[5] 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.[5, 6, 1]

Prognosis

The prognosis of episcleritis is favorable.[3]

Patient Education

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.

History

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

Many patients complain of acute onset of mild-to-moderate discomfort,[1] although some may notice only an area of painless injection.

Photophobia and watery discharge may be noted.

Physical

The diagnosis of episcleritis mainly based on clinical findings.

Slit-lamp examination reveals edema of  isthe 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.



View Image

Localized temporal inflammation in a patient with nodular episcleritis.

Other ocular findings that may be found in episcleritis include anterior uveitis and ocular hypertension.[5, 6]

Causes

Most cases are idiopathic[1] ; however, up to one third of cases may have an underlying systemic condition,[13, 14, 15] particularly connective tissue or vasculitic diseases.

Collagen-vascular diseases associated with episcleritis include the following:

Other noninfectious conditions associated with episcleritis include HLA-B27 associated,[16] Behcet disease, and sarcoidosis.[17] Gout, atopy, acne rosacea and VEXAS syndrome [18, 19] have also been associated with episcleritis. Episcleritis has also been recently reported to occur after vaccination against Covid-19. [20, 21] . A paradoxical adverse reaction to drugs such as etanercept may also lead to episcleritis. [22]

Foreign bodies may cause episcleritis.

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

Complications

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.[5] However, the latter two complications were seen only in patients with episcleritis based on a population-based study.[25]

Laboratory Studies

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

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

Imaging Studies

Evaluations of the sclera and episclera using anterior segment optical coherence tomography (AS-OCT) have been shown useful in monitoring the effectiveness of therapy.[26] Differentiating scleritis from episcleritis can be helpful. The former demonstrates increased thickness of the sclera and intrascleral hyporeflective areas of edema on AS-OCT.[27]

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.[28]

 

 

Procedures

Biopsy can be performed in atypical cases where the diagnosis is not clear. In rare cases, episcleritis can mimic a mass.[29]  On the other hand, malignancy can also present as episcleritis.[7]  

Approach Considerations

Topical lubricating drops are a standard choice in clinical practice to enhance patient comfort. In cases of ocular conditions requiring management, a short-term treatment with topical corticosteroids, such as prednisolone acetate 1% drops administered 4 times daily for a week, with gradual tapering over 3 to 4 weeks, or oral nonsteroidal anti-inflammatory drugs (NSAIDs), typically is recommended. Ophthalmologists usually are responsible for prescribing corticosteroids due to their potential side effects and need for close monitoring.[1]

Additionally, the use of topical vasoconstrictors like tetrahydrozoline or brimonidine tartrate 0.025% may be considered for aesthetic purposes, though their application should be sparing as prolonged and frequent use can lead to worsening erythema through rebound vasodilation. It is essential to exercise caution and consult with a healthcare professional, particularly regarding the controlled administration of vasoconstrictors to prevent adverse effects.[1]

Medical Care

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.[30] 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.[6]

Topical 0.1% tacrolimus drops was reported to be effective in steroid-resistant episcleritis. [31]

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.[6] About 20% of patients with nodular episcleritis require oral corticosteroid treatment.[25]

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

Activity

Sunglasses may be useful for patients with sensitivity to light.

Long-Term Monitoring

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.

Guidelines Summary

A clinical practice guideline for the treatment of scleritis and episcleritis by The Royal Victoria Eye and Ear Hospital Dublin is summarized below[32] :

Red flags

History

Examination

Investigations

Treatment

Follow-up

See the complete guideline for more information.[32]

Medication Summary

The goals of pharmacotherapy are to decrease pain, improve quality of life, to reduce morbidity, and to prevent complications.[33]

Dexamethasone ophthalmic (Maxidex)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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

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

Flurbiprofen

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  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

Clinical Context:  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)

Clinical Context:  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.

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.

What is episcleritis?What is the pathophysiology of episcleritis?What is the prevalence of episcleritis?What is the prognosis of episcleritis?What is included in patient education about episcleritis?Which clinical history findings are characteristic of episcleritis?Which physical findings are characteristic of episcleritis?What causes episcleritis?What are the possible complications of episcleritis?What are the differential diagnoses for Episcleritis?What is the role of lab testing in the workup of episcleritis?Which histologic findings are characteristic of episcleritis?What is the role of imaging studies in the management of episcleritis?How is episcleritis treated?What is included in topical therapy for episcleritis?What is the role of systemic therapy in the treatment of episcleritis?When are sunglasses indicated in the treatment of episcleritis?What is included in the long-term monitoring for episcleritis?What are the possible complications of long-term steroid therapy for the treatment of episcleritis?What is the goal of drug treatment for episcleritis?Which medications in the drug class Nonsteroidal Anti-inflammatory Agents are used in the treatment of Episcleritis?Which medications in the drug class Corticosteroids are used in the treatment of Episcleritis?

Author

Ellen N Yu-Keh, MD, Consulting Staff, Department of Ophthalmology, St Luke's Medical Center, Quezon City, Philippines

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

R Christopher Walton, MD, Adjunct Professor, Department of Ophthalmology, University of Texas Health Science Center at San Antonio

Disclosure: Nothing to disclose.

Chief Editor

Andrew A Dahl, MD, FACS, Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Disclosure: Nothing to disclose.

Additional Contributors

Andrew A Dahl, MD, FACS, Assistant Professor of Surgery (Ophthalmology), New York College of Medicine (NYCOM); Director of Residency Ophthalmology Training, The Institute for Family Health and Mid-Hudson Family Practice Residency Program; Staff Ophthalmologist, Telluride Medical Center

Disclosure: Nothing to disclose.

Hampton Roy, Sr, MD, † Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Disclosure: Nothing to disclose.

References

  1. Syed ZA. Conjunctival and Scleral Disorders. Porter RE. The Merck Manual of Diagnosis and Therapy. Rahway, NJ: Merck & Co Inc; Reviewed/Revised April 2023.
  2. Schonberg S, Stokkermans TJ. Episcleritis. StatPearls [Internet]. Available at https://www.ncbi.nlm.nih.gov/books/NBK534796/. August 7, 2023; Accessed: August 30, 2024.
  3. Thong LP, Rogers SL, Hart CT, Hall AJ, Lim LL. Epidemiology of episcleritis and scleritis in urban Australia. Clin Exp Ophthalmol. 2020 Aug. 48 (6):757-766. [View Abstract]
  4. Yadav S, Rawal G. Tubercular Nodular Episcleritis: A Case Report. J Clin Diagn Res. 2015 Aug. 9 (8):ND01-2. [View Abstract]
  5. Sainz de la Maza M, Molina N, Gonzalez-Gonzalez LA, Doctor PP, Tauber J, Foster CS. Clinical characteristics of a large cohort of patients with scleritis and episcleritis. Ophthalmology. 2012 Jan. 119 (1):43-50. [View Abstract]
  6. Berchicci L, Miserocchi E, Di Nicola M, La Spina C, Bandello F, Modorati G. Clinical features of patients with episcleritis and scleritis in an Italian tertiary care referral center. Eur J Ophthalmol. 2014 May-Jun. 24 (3):293-8. [View Abstract]
  7. Achibane A, Belghmaidi S, Elmansouri O, Hajji I, Moutaouakil A. Episcleritis as presenting sign of conjunctival lymphoma. J Fr Ophtalmol. 2021 Dec. 44 (10):e575-e577. [View Abstract]
  8. Foster CS, Maza MS. The Sclera. Springer-Verlag; 1994. 96-102.
  9. Watson PG, Hazelman BL. The Sclera and Systemic Disorders. Philadelphia: WB Saunders; 1976.
  10. Lin CP, Shih MH, Su CY. Scleritis. Surv Ophthalmol. 2006 May-Jun. 51(3):288-9; author reply 289. [View Abstract]
  11. Watson PG. Episcleritis. Current Ocular Therapy. 5th ed. 809.
  12. Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Ophthalmol. 1976. 60:163-192. [View Abstract]
  13. Minas TF, Podos SM. Familial glaucoma associated with elevated episcleral venous pressure. Arch Ophthalmol. 1968. 80:202-213. [View Abstract]
  14. Roy FH. Ocular Differential Diagnosis. 7th ed. Baltimore: Williams & Wilkins; 2002. Vol 1:
  15. Boniuk M. The ocular manifestations of ophthalmic vein and aseptic cavernous sinus thrombosis. Trans Am Acad Ophthalmol Otolaryngol. 1972 Nov-Dec. 76(6):1519-34. [View Abstract]
  16. Pathanapitoon K, Dodds EM, Cunningham ET Jr, Rothova A. Clinical Spectrum of HLA-B27-associated Ocular Inflammation. Ocul Immunol Inflamm. 2017 Aug. 25 (4):569-576. [View Abstract]
  17. Ungprasert P, Tooley AA, Crowson CS, Matteson EL, Smith WM. Clinical Characteristics of Ocular Sarcoidosis: A Population-Based Study 1976-2013. Ocul Immunol Inflamm. 2019. 27 (3):389-395. [View Abstract]
  18. Abumanhal M, Leibovitch I, Zisapel M, Eviatar T, Edel Y, Ben Cnaan R. Ocular and orbital manifestations in VEXAS syndrome. Eye (Lond). 2024 Jun. 38 (9):1748-1754. [View Abstract]
  19. Vitale A, Caggiano V, Martin-Nares E, Frassi M, et al. Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry. Semin Arthritis Rheum. 2024 Jun. 66:152430. [View Abstract]
  20. Sanjay S, Handa A, Kawali A, Shetty R, Bhakti Mishra S, Mahendradas P. Scleritis and Episcleritis following Coronavirus Disease (COVID-19) Vaccination. Ocul Immunol Inflamm. 2023 Aug. 31 (6):1184-1190. [View Abstract]
  21. Mahendradas P, Mishra SB, Sangoram R, Srinivasan S, Kawali A, Patil A, et al. Ocular manifestations following COVID-19 vaccination. J Ophthalmic Inflamm Infect. 2023 Sep 23. 13 (1):44. [View Abstract]
  22. Küçükali B, Gezgin Yıldırım D, Esmeray Şenol P, Özdemir HB, Bakkaloğlu SA. Etanercept-associated episcleritis: a pediatric case report of a paradoxical adverse reaction and review of the literature. Clin Rheumatol. 2024 Feb. 43 (2):799-808. [View Abstract]
  23. Otaif W, Al Somali AI, Al Habash A. Episcleritis as a possible presenting sign of the novel coronavirus disease: A case report. Am J Ophthalmol Case Rep. 2020 Dec. 20:100917. [View Abstract]
  24. Bostanci Ceran B, Ozates S. Ocular manifestations of coronavirus disease 2019. Graefes Arch Clin Exp Ophthalmol. 2020 Sep. 258 (9):1959-1963. [View Abstract]
  25. Homayounfar G, Borkar DS, Tham VM, Nardone N, Acharya NR. Clinical characteristics of scleritis and episcleritis: results from the pacific ocular inflammation study. Ocul Immunol Inflamm. 2014 Oct. 22 (5):403-4. [View Abstract]
  26. Axmann S, Ebneter A, Zinkernagel MS. Imaging of the Sclera in Patients with Scleritis and Episcleritis using Anterior Segment Optical Coherence Tomography. Ocul Immunol Inflamm. 2015 Aug 10. 1-6. [View Abstract]
  27. Shoughy SS, Jaroudi MO, Kozak I, Tabbara KF. Optical coherence tomography in the diagnosis of scleritis and episcleritis. Am J Ophthalmol. 2015 Jun. 159 (6):1045-1049.e1. [View Abstract]
  28. Hau SC, Devarajan K, Ang M. Anterior Segment Optical Coherence Tomography Angiography and Optical Coherence Tomography in the Evaluation of Episcleritis and Scleritis. Ocul Immunol Inflamm. 2021 Feb 17. 29 (2):362-369. [View Abstract]
  29. Zhou L, Wang J, Xu G, Wang D, Wang X, Chen Z. A case of nodular episcleritis mimicking a solitary giant episcleral mass. Eur J Ophthalmol. 2021 Oct 16. 11206721211052879. [View Abstract]
  30. Williams CP, Browning AC, Sleep TJ. A randomised, double-blind trial of topical ketorolac vs artificial tears for the treatment of episcleritis. Eye. Sep 2004. [View Abstract]
  31. Alghamdi AH Sr. Treatment of Steroid-Resistant Nodular Episcleritis With Tacrolimus: A Case Report. Cureus. 2023 Oct. 15 (10):e47057. [View Abstract]
  32. [Guideline] The Royal Victoria Eye and Ear Hospital Dublin. Clinical Guideline for the Treatment of Scleritis and Episcleritis. The Royal Victoria Eye and Ear Hospital Dublin. Available at https://www.rveeh.ie/app/uploads/2022/06/Clinical-Guideline-Scleritis-and-Episcleritis-Final-2022.pdf. 2022; Accessed: October 3, 2024.
  33. Lim L, Suhler EB, Smith JR. Biologic therapies for inflammatory eye disease. Clin Experiment Ophthalmol. 2006 May-Jun. 34(4):365-374. [View Abstract]

Localized temporal inflammation in a patient with nodular episcleritis.

Localized temporal inflammation in a patient with nodular episcleritis.