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Scleritis


BASICS


DESCRIPTION


  • Scleritis is a painful, inflammatory process of the sclera, part of the eye 's outer coat.
    • Categorized into anterior or posterior and diffuse, nodular, or necrotizing
    • Commonly associated with systemic disorders
    • Frequently requires systemic anti-inflammatory therapy
    • Potentially vision-threatening
  • In contrast, episcleritis is a self-limited inflammation of the eye with only mild discomfort.
  • System(s) affected: ocular

EPIDEMIOLOGY


  • Predominant age: most frequently occurs in 4th and 6th decades; mean age for all types of scleritis is ¢ ˆ ¼52 years.
  • Predominant sex: female > male (1.6:1)

Incidence
  • Anterior scleritis, about 94% of cases (1)[B]
    • Diffuse anterior scleritis (most common)
  • Remaining 6% have posterior scleritis

Prevalence
Estimated to be 6 cases/100,000 people in the general population ‚  

ETIOLOGY AND PATHOPHYSIOLOGY


  • Frequently associated with a systemic illness (1)[B]
    • Most commonly associated with rheumatoid arthritis
    • In about 38% of cases, scleritis is the presenting manifestation of an underlying systemic disorder.
    • Necrotizing scleritis has the highest association with systemic disease.
  • Other etiologies
    • Proposed pathogenesis is dependent on type of scleritis. In necrotizing scleritis, the predominant mechanism is likely due to the activity of matrix metalloproteinases.
    • Drug-induced scleritis has been reported in patients on bisphosphonate therapy.
    • Surgically induced necrotizing scleritis is exceedingly rare and occurs after multiple surgeries.
    • Infectious scleritis occurs most commonly after surgical trauma, and Pseudomonas aeruginosa in poorly controlled diabetic patients is the most common causative organism (2)[B].

RISK FACTORS


Individuals with autoimmune disorders are most at risk. ‚  

COMMONLY ASSOCIATED CONDITIONS


  • Rheumatoid arthritis
  • Sj ƒ ¶gren syndrome
  • Granulomatosis with polyangitis
  • Ankylosing spondylitis
  • Systemic lupus erythematosus
  • Reactive arthritis
  • Relapsing polychondritis
  • Polyarteritis nodosa
  • Sarcoidosis
  • Inflammatory bowel disease
  • Herpes zoster
  • Herpes simplex
  • HIV
  • Syphilis
  • Lyme disease
  • Tuberculosis

DIAGNOSIS


HISTORY


  • Redness and inflammation of the sclera
    • Can be bilateral in about 40% of cases (1)[B]
  • Decrease in visual acuity of two or more Snellen lines occurred in about 16% of patients (1)[B].
  • Photophobia and tearing
  • Pain ranging from mild discomfort to extreme localized tenderness
    • May be described as constant, deep, boring, or pulsating
    • Pain may be referred to the eyebrow, temple, or jaw.
    • Pain may awaken patient from sleep in early hours of morning.
    • Severe pain is most commonly associated with necrotizing scleritis (1)[B].

PHYSICAL EXAM


  • Examine sclera in all directions of gaze by gross inspection.
    • A bluish hue may suggest thinning of sclera.
    • Inspect for breadth and degree of injection.
  • Check visual acuity.
  • Slit-lamp exam using red-free light
    • Episcleritis: conjunctival and superficial vascular plexuses displaced anteriorly
    • Scleritis: Deep episcleral plexus is the maximum site of vascular congestion, displaced anteriorly d/t edema of underlying sclera. Characteristic blue or violet color, absent in patients with episcleritis
  • Ocular tenderness
  • Dilated fundus exam to rule out posterior involvement
  • A complete physical exam, particularly of the skin, joints, heart, and lungs, should be done to evaluate for associated conditions.

DIFFERENTIAL DIAGNOSIS


  • Conjunctivitis
  • Episcleritis
  • Iritis (anterior uveitis)
  • Blepharitis
  • Trauma
  • Ocular rosacea
  • Herpes zoster

DIAGNOSTIC TESTS & INTERPRETATION


  • Consider further tests if warranted by history and physical.
  • Routine tests to exclude systemic disease
    • CBC, serum chemistry, urinalysis, ESR, and/or C-reactive protein
  • Specific tests for underlying systemic illness
    • Rheumatoid factor, anticyclic citrullinated peptide antibodies, antineutrophil cytoplasmic antibody, and antinuclear antibody may aid in the diagnosis.
  • Other tests:
    • Fluorescent treponemal antibody absorption (FTA-ABS), rapid plasma reagin, and Lyme titers
  • Further imaging studies, such as a chest x-ray and sacroiliac joint films, may be useful if a specific systemic illness is suspected.
  • B-scan US to detect posterior scleritis and thickness of sclera
  • If indicated, MRI/CT scan to detect orbital disease

Diagnostic Procedures/Other
Biopsy is not routinely required unless diagnosis remains uncertain after above investigations. ‚  
Test Interpretation
Different subtypes of scleritis are associated with varying presentations and distinct findings. ‚  
  • Diffuse anterior scleritis: widespread inflammation
  • Nodular anterior scleritis: immovable, inflamed nodule
  • Necrotizing anterior scleritis
    • "With inflammation " : Sclera becomes transparent.
    • Scleromalacia perforans without inflammation: painless and often associated with rheumatoid arthritis
  • Posterior scleritis: associated with retinal and choroidal complications, adjacent swelling of orbital tissues may occur

TREATMENT


GENERAL MEASURES


If scleral thinning, glasses/eye shield should be worn to prevent perforation. ‚  

MEDICATION


  • First-line therapies for noninfectious scleritis (3)[C]
    • Oral NSAID therapy, choice based on availability, example is ibuprofen 600 to 800 mg PO TID " “QID provided no contraindications exists. About 37% successful (4)[B]
    • Topical steroids as adjunct; prednisolone acetate 1% ophthalmic suspension
    • Subconjunctival triamcinolone acetonide injection only for nonnecrotizing, 40 mg/mL, 97% improvement after one injection. Increased risk of ocular HTN, cataract, and globe perforation (5)[B]
    • Systemic steroids (initial if necrotizing scleritis and preferentially IV if vision threatening, otherwise use if failure of NSAIDs), prednisone 40 to 60 mg PO QD, taper over 4 to 6 weeks
    • Antimetabolites including methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, and cyclosporine may be used as steroid-sparing agents. They are generally recommended if steroids cannot be tapered below 10 mg PO QD (4)[C].
  • Second-line therapies (4)[C],(5)[B],(6)[A]
    • Immunomodulatory agents, infliximab, and adalimumab can be used if patient has failed or is not a candidate for antimetabolites or calcineurin inhibitors. These agents are preferred over etanercept due to higher treatment success.
  • Necrotizing anterior scleritis and posterior scleritis
    • May require immunosuppressive therapy in addition to systemic steroids
    • Treat aggressively due to possible complications if left untreated. May need patch grafting to maintain globe integrity
  • Infectious
    • Antibiotic therapy resolves about 18% of cases, whereas the remaining often requires surgical intervention such as debridement (2)[B].

ISSUES FOR REFERRAL


  • All patients with scleritis should be managed by an ophthalmologist familiar with this condition.
  • Rheumatology referral for coexistent systemic disease is helpful for long-term success.

ADDITIONAL THERAPIES


Immunosuppressants used for autoimmune and collagen vascular disorders may be of help in active scleritis. ‚  

SURGERY/OTHER PROCEDURES


  • In rare cases, scleral biopsy may be indicated to confirm infection or malignancy.
  • Ocular perforation requires scleral grafting.

ONGOING CARE


Follow-Up Tests & Special Considerations


  • No restrictions
  • Avoid contact lens " ”wear only if there is corneal involvement, which is rare.

Patient Monitoring
  • Patient in the active stage of inflammation should be followed very closely by an ophthalmologist to assess the effectiveness of therapy.
  • Medication use mandates close surveillance for adverse effects.

DIET


No special diet ‚  

PATIENT EDUCATION


Scleritis at PubMed Health: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024411/ ‚  

PROGNOSIS


Scleritis is indolent, chronic, and often progressive. ‚  
  • Diffuse anterior scleritis (best prognosis)
  • Necrotizing anterior scleritis (worst prognosis)
  • Recurrent bouts of inflammation may occur.
  • Scleromalacia perforans has the highest risk of perforation of the globe.

COMPLICATIONS


  • Decrease in vision, anterior uveitis, ocular hypertension, and peripheral keratitis (1)[B]
  • Cataract and glaucoma can result from disease or treatment with steroids.
  • Ocular perforation can occur in severe stages.

REFERENCES


11 Sainz de la Maza ‚  M, Molina ‚  N, Gonzalez-Gonzalez ‚  LA, et al. Clinical characteristics of a large cohort of patients with scleritis and episcleritis. Ophthalmology.  2012;119(1):43 " “50.22 Hodson ‚  KL, Galor ‚  A, Karp ‚  CL, et al. Epidemiology and visual outcomes in patients with infectious scleritis. Cornea.  2013;32(4):466 " “472.33 Beardsley ‚  RM, Suhler ‚  EB, Rosenbaum ‚  JT, et al. Pharmacotherapy of scleritis: current paradigms and future directions. Expert Opin Pharmacother.  2013;14(4):411 " “424.44 Sainz de la Maza ‚  M, Molina ‚  N, Gonzalez-Gonzalez ‚  LA, et al. Scleritis therapy. Ophthalmology.  2012;119(1):51 " “58.55 Sohn ‚  EH, Wang ‚  R, Read ‚  R, et al. Long-term, multicenter evaluation of subconjunctival injection of triamcinolone for non-necrotizing, noninfectious anterior scleritis. Ophthalmology.  2011;118(10):1932 " “1937.66 Levy-Clarke ‚  G, Jabs ‚  DA, Read ‚  RW, et al. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology.  2014;121(3):785 " “796.e3.

ADDITIONAL READING


  • Doctor ‚  P, Sultan ‚  A, Syed ‚  S, et al. Infliximab for the treatment of refractory scleritis. Br J Ophthalmol.  2010;94(5):579 " “583.
  • Iaccheri ‚  B, Androudi ‚  S, Bocci ‚  EB, et al. Rituximab treatment for persistent scleritis associated with rheumatoid arthritis. Ocul Immunol Inflamm.  2010;18(3):223 " “225.
  • Rachitskaya ‚  A, Mandelcorn ‚  ED, Albini ‚  TA. An update on the cause and treatment of scleritis. Curr Opin Ophthalmol.  2010;21(6):463 " “467.
  • Wakefield ‚  D, Di Girolamo ‚  N, Thurau ‚  S, et al. Scleritis: challenges in immunopathogenesis and treatment. Discov Med.  2013;16(88):153 " “157.
  • Wakefield ‚  D, Di Girolamo ‚  N, Thurau ‚  S, et al. Scleritis: immunopathogenesis and molecular basis for therapy. Prog Retin Eye Res.  2013;35:44 " “62.

CODES


ICD10


  • H15.009 Unspecified scleritis, unspecified eye
  • H15.019 Anterior scleritis, unspecified eye
  • H15.039 Posterior scleritis, unspecified eye
  • H15.099 Other scleritis, unspecified eye
  • H15.059 Scleromalacia perforans, unspecified eye
  • H15.051 Scleromalacia perforans, right eye
  • H15.003 Unspecified scleritis, bilateral
  • H15.002 Unspecified scleritis, left eye
  • H15.031 Posterior scleritis, right eye
  • H15.012 Anterior scleritis, left eye
  • H15.013 Anterior scleritis, bilateral
  • H15.001 Unspecified scleritis, right eye
  • H15.052 Scleromalacia perforans, left eye
  • H15.093 Other scleritis, bilateral
  • H15.033 Posterior scleritis, bilateral
  • H15.011 Anterior scleritis, right eye
  • H15.091 Other scleritis, right eye
  • H15.053 Scleromalacia perforans, bilateral
  • H15.092 Other scleritis, left eye
  • H15.032 Posterior scleritis, left eye

ICD9


  • 379.00 Scleritis, unspecified
  • 379.03 Anterior scleritis
  • 379.07 Posterior scleritis
  • 379.09 Other scleritis and episcleritis
  • 379.05 Scleritis with corneal involvement
  • 379.04 Scleromalacia perforans

SNOMED


  • 78370002 Scleritis (disorder)
  • 63454000 Anterior scleritis (disorder)
  • 267660007 Posterior scleritis (disorder)
  • 95797003 Necrotizing scleritis
  • 42574005 Scleritis with corneal involvement (disorder)
  • 26664005 Scleromalacia perforans (disorder)

CLINICAL PEARLS


  • Episcleritis is a self-limited inflammation of the eye with mild discomfort. Scleritis is a painful, severe, and potentially vision-threatening condition. Both conditions can be associated with underlying inflammatory diseases.
  • About 35% of all cases of scleritis are associated with a systemic disease such as rheumatoid arthritis. Necrotizing scleritis has the highest association.
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