The onset of posterior scleritis has very few, and in some instances no physical signs, and the diagnosis can be challenging. Moreover, because posterior scleritis can present as a choroidal mass, serous retinal detachment, retinal striae or retinal and disc edema, it is confused with other diseases of the posterior segment. The most common presenting clinical feature is decreased vision with pain and diplopia, flashes, and limitation of ocular movements can be present. Because of the close connection between the sclera and Tenon’s capsule, inflammation of the posterior sclera can extend to the orbit and cause proptosis, chemosis, lid swelling and retraction in upgaze. The diagnosis is made by B-scan ultrasonography, which will demonstrate thickening, edema of the posterior sclera, and a ‘T’ sign when edema of the Tenon’s space and the adjacent optic nerve occurs. The association of posterior scleritis with systemic disease is less compared to the anterior form, however, it is still significant and patients need to undergo a systemic evaluation.7–9,11
The evaluation of a patient with scleritis requires a systemic evaluation. This should start with a thorough medical history with an extensive review of systems and a physical examination, in addition to a full ophthalmic examination. Infectious etiologies also should be considered and a history of trauma or surgical insult should be sought.10,11
Approximately 50–60% of patients with scleritis will have an underlying associated disease (see Table 1). Of these, 50% will be an autoimmune connective tissue or vasculitic disease and 50% of the patients presenting with necrotizing scleritis will have a mortality rate of 50–60% within five years of onset of disease, if not properly immunosuppressed. Therefore, early diagnosis and treatment is critical for a good ocular and systemic prognosis of patients with scleritis.
Laboratory tests for suspected systemic diseases in patients with scleritis must be target-oriented, based on the data generated from a comprehensive medical and ophthalmic examination. It should be emphasized that many systemic diseases do not have specific laboratory tests, and that diagnosis can only be made on the basis of the clinical and biological findings.
All patients with a new diagnosis of scleritis should undergo evaluation for the presence of a systemic vasculitis. Routine testing typically includes complete blood count, complete metabolic panel, urinalysis with microscopic analysis, perinuclear and cytoplasmic anti-neutrophil cytoplasmic antibody, and chest X-ray. Infections including syphilis and Lyme disease should be ruled out with a rapid plasma reagin test, fluorescent treponemal antibody, and a Lyme antibody.1,8–11
More directed evaluations may be ordered based on the history and physical examination. Most patients with RA and systemic lupus erythematosus carry their diagnosis prior to presenting with scleritis and, therefore, obtaining an antinuclear antibody or rheumatoid factor level may not be necessary unless dictated by the history and physical examination. Other potential directed tests may include a tuberculin skin test, sacroiliac joint X-rays (for spondyloarthropathy), sinus imaging (for Granulomatosis with polyangiitis), and viral hepatitis panel (hepatitis B for polyarteritis nodosa and hepatitis C for cryoglobulinemia). In any case of suspected infectious scleritis, cultures and/or scleral biopsy may be needed to secure the diagnosis.1,8–11
The pathology and pathogenesis of scleritis are multifactorial and complex. Inflammatory responses in the sclera can be granulomatous or nongranulomatous. This is in part determined by the cause of the scleritis, which can be infectious or autoimmune.
Although rare, infectious scleritis results from the direct invasion of the infectious agent, which triggers an inflammatory response and local tissue damage. Organisms that have been associated with scleral infections include herpes, syphilis, mycobacterium, acanthamoeba, bacteria (pseudomona), and fungi.1,11
In autoimmune disorders, a hypersensitivity reaction is generated against autoantigens, which leads to a cellular immunological attack against healthy tissue and vessels. The immunological mechanisms involved in scleritis are described by the Type III (immune-complex mediated) and Type IV (cell mediated) hypersensitivity reactions that leads to inflammatory microangiopathy and direct cellular damage of affected scleral tissue and vessels. Vessel occlusion and ischemia contribute to tissue damage and necrosis. The response to the inflammatory insult results in the activation of local mechanisms that lead to the degradation of proteoglycans and collagen, which eventually results in the thinning and loss of scleral tissue.11
The treatment of scleritis requires the use of systemic immunomodulatory therapy (IMT). A step-ladder approach should be instituted for the treatment of scleritis and this can be adjusted depending on the severity of the presentation and specific diagnosed systemic disease. Diffuse, nodular or posterior scleritis can be initially treated with systemic non-steroidal anti-inflammatory drugs (NSAIDs) following the medical and pharmacological recommendations. Glucocorticoids should be used when failure of NSAIDs occurs or in cases when rapid control of destructive inflammation is needed. Based upon our clinical experience, we recommend initial therapy with prednisone 40–60 mg/day. The use of prednisone should be limited and chronic use needs to be avoided. Usually this regimen is continued for the first four weeks of therapy with ongoing assessment of clinical response.
If failure or chronic dependence to prednisone is developed, the use of immunosuppressive therapy drugs IMT may be added or substituted as third-line therapy. Moreover, IMT may be the initial choice in necrotizing scleritis.12
There are no randomized trials in scleritis on which to base the choice of the specific immunosuppressive medication. Also, new IMT and biologic response modifiers (BRM), mainly antitumor necrosis factor alfa (TNFα), rituximab (RTX) and adalimumab, may be effective in refractory scleritis.12–18
Systemic steroid-sparing agents that have been used with success in the treatment of necrotizing and chronic scleritis include methotrexate, azathioprine, cyclosporine, cotrimoxazole, mycophenolate mofetil, and cyclophosphamide.
Because of the proven effectiveness of both RTX and cyclophosphamide in patients with granulomatosis with polyangiitis, the first-line immunosuppressive medication in the treatment of scleritis is typically one of these agents.12,14,19–21
RTX is a chimeric mouse monoclonal antibody that directly targets the CD20 antigen expressed on the majority of B cells. There is increasing evidence that RTX can be employed to successfully treat ocular inflammatory disease.13 Given the frequency of severe scleritis as a manifestation of granulomatosis with polyangiitis and the strong evidence that RTX is effective in this setting, it is reasonable to extrapolate the efficacy of RTX to scleritis. The use of cyclophosphamide or RTX as a first line therapy should be considered in necrotizing scleiritis associated with systemic vasculitis, as this will also decrease the risk of death in these patients. For patients with disease refractory to RTX, we suggest cyclophosphamide (2 mg/kg per day, with dose adjustments for patients with decreased renal function). Progressive scleral melting will require scleral grafting surgery and systemic chemotherapy.13,16