Episcleritis, Scleritis, and Keratitis

Theresa Larson

Shilpa Kodati

H. Nida Sen

EPISCLERITIS

Episcleritis is a self-limiting, generally benign inflammation of the episclera.

Etiology and Epidemiology

• Episcleritis occurs most frequently in young to middle-aged women (20 to 40 years old).

• It is more commonly unilateral (50% to 80%).

• The etiology is unknown in most cases, but it is believed to be immune mediated, and can be associated with systemic disease.

Differential Diagnosis

• Scleritis

Compared to scleritis, episcleritis has minimal pain, is less commonly associated with systemic disease, and has a more benign, self-limiting course.

• Pinguecula

• Phlyctenule

• Subconjunctival hemorrhage

• Primary conjunctival malignancy or lymphoma

• Anterior uveitis

Diagnostic Evaluation

• Most cases are idiopathic, although approximately one-third of patients are found to have an underlying systemic disease (rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, granulomatosis with polyangiitis (Wegener granulomatosis), or psoriasis).

• A thorough review of systems is indicated and a targeted systemic workup is necessary in recurrent cases.

• Associated ocular conditions include dry eye, ocular rosacea, and atopic keratoconjunctivitis.

Treatment

• Episodes are usually self-limiting, and patients can be observed without treatment. Artificial tears can be used for symptomatic relief.

• If the patient is very symptomatic or has a more severe presentation, treatment options include topical nonsteroidal anti-inflammatory drugs (NSAIDs), topical corticosteroids, and, in refractory cases, oral NSAIDs.

• If the episcleritis does not resolve with treatment, an alternative diagnosis, such as masquerade syndromes, should be considered.

FIGURE 3-1. Episcleritis. A. This patient has episcleritis with a salmon pink hue. B. The figure on the right demonstrates the same eye with blanching of the episclera after 10% phenylephrine.

FIGURE 3-2. Episcleritis. This patient has focal injection: (A) before and (B) after administration of topical 10% phenylephrine.

Prognosis

• The prognosis is usually very good in isolated cases of episcleritis, although anterior uveitis and corneal involvement can occur concurrently.

• Episodes may reoccur, but only rarely result in lasting sequelae (Figs. 3-1 and 3-2).

REFERENCES

Foster CS, Sainz de la Maza M. Clinical consideration of episcleritis and scleritis. In: The Sclera. New York, NY: Springer-Verlag; 1994:107.

Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and treatment results. Am J Ophthalmol. 2000;130:469-476.

Sainz de la Maza M, Jabbur NS, Foster CS. Severity of scleritis and episcleritis. Am J Ophthalmol. 1994;101: 389-396.

SCLERITIS

Shilpa Kodati

Theresa Larson

H. Nida Sen

Scleritis is characterized by inflammation and edema of scleral and episcleral tissue. It is classified anatomically as either anterior (>90% cases) or posterior (Table 3-1).

ANTERIOR SCLERITIS

Etiology and Epidemiology

• Scleritis is most common in middle-aged women (40 to 60 years old) with approximately 70% of overall cases occurring in women and 30% in men.

• Anterior scleritis is further classified into: diffuse, nodular, necrotizing with inflammation, and necrotizing without inflammation (scleromalacia perforans).

• Necrotizing scleritis is the most severe and destructive form of scleritis and the type most often associated with sight-threatening sequelae.

• About 25% to 40% of patients have a history of systemic disease, most commonly rheumatoid arthritis (Table 3-2). The risk of an underlying systemic disease is higher in patients with necrotizing scleritis (˜50% have a systemic disease).

• Bisphosphonates, erlotinib, and procainamide have been reported to be associated with drug-induced scleritis.

• Infectious scleritis is rare and typically occurs after ophthalmic surgery or trauma. Bacteria are the most commonly reported causative microbe.

Signs

• The sclera has a violaceous hue in natural light with inflamed vessels that cannot be moved with a cotton-tipped applicator. It is easier to appreciate scleritis by looking at the eye without the slit lamp.

• Areas of repeated attacks may demonstrate scleral thinning with a bluish hue of the underlying choroid.

• Necrotizing scleritis has a white avascular area surrounded by injection and edema.

• Topical (10%) phenylephrine will not blanch the vessels in scleritis.

• Scleritis can be associated with peripheral keratitis (more common in the necrotizing subtype) and anterior uveitis (Figs. 3-3, 3-4, 3-5, 3-6, 3-7, 3-8, 3-9, 3-10, 3-11 and 3-12).

Differential Diagnosis

• Episcleritis

• Subconjunctival hemorrhage

• Conjunctival mucosa-associated lymphoid tissue lymphoma

• Anterior uveitis or panuveitis

• Acute angle-closure glaucoma

• Keratitis

• Endophthalmitis

• Carotid or dural sinus fistula

Diagnostic Evaluation

• Given that the onset of scleritis can precede the diagnosis of a systemic disease, a thorough history and careful review of systems is needed. The history and review of systems will ultimately guide diagnostic testing, although recurrent cases of scleritis
and all cases of necrotizing scleritis should be worked up.

TABLE 3-1. Scleritis Clinical Subtypes and Their Prevalence

Anterior scleritis
	Diffuse	40%-45%
	Nodular	40%
Necrotizing scleritis
	With inflammation	10%
	Without inflammation (scleromalacia perforans)	1%-5%
Posterior scleritis		1%-5%
Adapted from Nussenblatt RB, Whitcup SM. Uveitis: Fundamentals and Clinical Practice. 4th ed. Philadelphia, PA: Elsevier; 2010.

TABLE 3-2. Systemic Disease Associations

Noninfectious		Infectious	Other
Connective Tissue Disease		Herpes zoster ophthalmicus	Gout
	Rheumatoid arthritis	Herpes simplex keratitis	Rosacea
	Juvenile rheumatoid arthritis	Acanthamoeba keratitis	Foreign body reaction Drugs (bisphosphonates)
	Reiter syndrome	Syphilis	Foreign body reaction Drugs (bisphosphonates)
	Systemic lupus erythematosus	Lyme disease
	Relapsing polychondritis	Bartonellosis
	Polymyositis	Tuberculosis
	Inflammatory bowel disease	Pseudomonas aeruginosa
	Spondyloarthropathy
Vasculitides
	Granulomatosis with polyangiitis (Wegener granulomatosis)
	Polyarteritis nodosa
	Allergic angiitis of Churg-Strauss
	Cogan syndrome
	Takayasu disease
	Adamantiades-Behçet disease
	Sarcoidosis

Rheumatoid factor, anti-citrullinated cyclic protein, classical antineutrophil cytoplasmic antibody, protoplasmic-staining antineutrophil cytoplasmic antibody (p-ANCA), myeloperoxidase, antinuclear antibody (ANA), and antidouble stranded DNA, may be considered if an underlying rheumatologic disease is suspected.

• Rule out infectious causes with the appropriate tests, including rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL), fluorescent treponemal antibody absorption (FTA-Abs) or syphilis immunoglobulin G (IgG), purified protein derivative (PPD), and/or QuantiFERON-TB Gold. Orbital computed tomography should be considered in atypical cases or cases of suspected orbital inflammatory syndrome.

Treatment

• Oral NSAIDs (indomethacin 25 to 50 mg three times daily, ibuprofen 600 to 800 mg three to four times daily) and/or topical corticosteroid drops are considered first-line therapy for mild-to-moderate cases. The duration of therapy is usually between 4 and 8 weeks.

• Oral prednisone (starting dose of 1 mg/kg, up to 60 mg) is indicated for more severe cases or for patients not responding to NSAIDs or topical therapy and tapered depending on the response to therapy.

• Subconjunctival injection of triamcinolone is also an option in non-necrotizing scleritis.

• Immunomodulatory treatment (IMT) is used in severe cases, recurrent disease, and necrotizing scleritis. Methotrexate is commonly used as a first-line IMT in patients with idiopathic scleritis. Antitumor necrosis factor (anti-TNF) agents or rituximab is usually used in cases of methotrexate or other antimetabolite treatment failures.

• Scleritis associated with an underlying autoimmune disease is usually an indication for treatment. Patients with necrotizing scleritis associated with a systemic disorder, such as granulomatosis with polyangiitis (Wegener granulomatosis), generally require IMT because of the high mortality rate without systemic treatment.

• Infectious scleritis is treated with a combination of topical and systemic antimicrobial therapy. The majority of cases also require surgical intervention, including debridement, patch graft placement, and removal of infected hardware.

Prognosis

• The prognosis varies based on the site of inflammation, associated complications, underlying conditions, and response to therapy. Diffuse anterior scleritis has the best prognosis, whereas necrotizing scleritis has the worst prognosis with the highest rates of visual loss and complications.

REFERENCES

Hodson, KL, Galor A, Karp CL, et al. Epidemiology and visual outcomes in patients with infectious scleritis. Cornea. 2013;32:466-472.

Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and treatment results. Ophthalmology. 2000;130:469-476.

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;119:43-50.

Stern MS, Todorich, B, Faia LJ. Ocular pharmacology for scleritis: review of treatment and a practical perspective. J Ocul Pharmacol Ther. 2017;4:240-246.

POSTERIOR SCLERITIS

Posterior scleritis is an inflammation of the sclera that begins posterior to the ora serrata and involves the posterior aspect of the eye.

Etiology and Epidemiology

• Accounts for <10% of scleritis cases; however, it is often underrecognized because of its nonspecific presentation.

Differential Diagnosis

• Choroidal tumors

• Uveal effusion syndrome

• Rhegmatogenous retinal detachment

• Vogt-Koyanagi-Harada syndrome

• Central serous chorioretinopathy

• Optic neuritis

• Masquerade syndromes (lymphoma, metastatic carcinoma, and choroidal melanoma)

Diagnostic Evaluation

• Laboratory evaluation for an underlying systemic disease is warranted based on the results of a thorough history and review of systems.

Rule out treatable infectious causes such as syphilis and tuberculosis (RPR or VDRL, FTA-Abs or syphilis IgG, PPD, and QuantiFERON-TB Gold)

• B-scan: This is very helpful to establish the diagnosis. It demonstrates scleral wall thickness >2 mm in either a diffuse or nodular manner. A T-sign (present in approximately 40% of cases of posterior scleritis) represents a sonographically empty space due to edema surrounding Tenon capsule and the optic nerve.

• Fluorescein and indocyanine green angiography can be performed to exclude other causes, such as Vogt-Koyanagi-Harada syndrome and sarcoidosis.

FIGURE 3-3. Scleritis. Diffuse anterior scleritis is characterized by inflammation of the deep scleral and episcleral vessels, which have a dark red/violaceous hue.

Prognosis

• The prognosis depends on the timeliness of treatment and severity of disease. Patients older than 50 years, patients with an associated systemic disease, and those requiring more aggressive treatment have a greater risk of vision loss.

REFERENCES

Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and scleritis: clinical features and treatment results. Ophthalmology. 2000;130:469-476.

Lavric A, Gonzalez-Lopez JJ, Majumder PD, et al. Posterior scleritis: analysis of epidemiology, clinical factors, and risk of recurrence in a cohort of 114 patients. Ocul Immunol Inflamm. 2016;24(1):6-15.

FIGURE 3-4. Scleritis. Diffuse anterior scleritis with inferotemporal thinning. Note the scleral injection and adjacent scleral thinning recognized by the blue color of the underlying choroid.

FIGURE 3-5. Nodular scleritis. Nodular scleritis and peripheral ulcerative keratitis. The immobile nodule is surrounded by scleral injection. There is a focal, peripheral corneal opacity resulting from past episodes of peripheral ulcerative keratitis.

FIGURE 3-6. Necrotizing scleritis. Necrotizing scleritis in a patient with granulomatosis with polyangiitis with one suture remaining from a past scleral biopsy. Note the white, avascular patch of sclera with surrounding temporal thinning.

FIGURE 3-7. Scleromalacia perforans. An elderly woman with poorly treated rheumatoid arthritis that caused painless scleral thinning through which the underlying blue choroid is visible (necrotizing scleritis without inflammation, or scleromalacia perforans). (Courtesy Sunir J. Garg, MD.)

FIGURE 3-8. A patient with posterior scleritis. A. There are horizontal choroidal folds consistent with a mass (in this case, scleral inflammation) behind the globe. B. The fluorescein angiogram showing the choroidal striations. (Courtesy of William Benson, MD.)

FIGURE 3-9. Posterior scleritis. Posterior scleritis causes disruption of the normal choroidal circulation as well as restriction of scleral outflow through the vortex veins. This causes subsequent dysfunction of the retinal pigment epithelium. A. This can result in a serous retinal detachment. Fluorescein angiography demonstrating (B) pinpoint choroidal leakage with (C) pooling of dye in the late frames. D. B-scan ultrasonography demonstrating thickening of the sclera and choroid (arrows) with edema of Tenon capsule behind the globe, which along with the optic nerve, creates the “T-sign.” (Courtesy William Benson, MD and Eliza Hoskins, MD.)

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