PATHOGENESIS

A much more severe ocular inflammatory condition than episcleritis, scleritis is caused by an immune-mediated (typically immune-complex) vasculitis that frequently leads to destruction of the sclera. Scleritis is often associated with an underlying systemic immunologic disease; about one-third of patients with diffuse or nodular scleritis and two-thirds of patients with necrotizing scleritis have a detectable connective tissue or auto-immune disease; the different forms of scleritis are discussed in the following subsections.

CLINICAL PRESENTATION

Scleritis occurs most often in the fourth to sixth decades of life, is more common in women, and is exceedingly rare in children. About one-half of scleritis cases are bilateral at some time in their course. The onset of scleritis is usually gradual, extending over several days. Most patients with scleritis experience severe boring ocular pain, which may worsen at night and occasionally awaken them from sleep. The pain may be referred to other regions of the head or face on the involved side, and the globe is often tender. The inflamed sclera has a violaceous hue, which is best seen in sunlight. Inflamed scleral vessels have a crisscross pattern, adhere to the sclera, and cannot be moved with a cotton-tipped applicator. Scleral edema, often with overlying episcleral edema, is noted by slit-lamp examination. Scleritis may lead to structural alterations of the globe, with attendant visual morbidity. Scleritis can be classified clinically based on the anatomical location (anterior versus posterior sclera) and appearance of the scleral inflammation (Table 11-4). See BCSC Section 4, Ophthalmic Pathology and Intraocular Tumors, for histologic correlation.

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(1):43–50.

Table 11-4 Subtypes and Prevalence of Scleritis

LABORATORY EVALUATION

Scleritis can occur in association with various systemic infectious diseases, including syphilis, tuberculosis, herpes zoster, Lyme disease, “cat-scratch” disease, and leprosy (Hansen disease). It is most frequently seen, however, in association with autoimmune or connective tissue diseases such as rheumatoid arthritis, systemic lupus erythematosus, and seronegative spondyloarthropathies (eg, ankylosing spondylitis) or secondary to vasculitides such as granulomatosis with polyangiitis (Wegener granulomatosis), polyarteritis nodosa, and giant cell arteritis. Metabolic diseases such as gout may also, in rare instances, be associated with scleritis. More than 50% of patients with scleritis have an identifiable associated systemic disease. The differential diagnosis of scleritis is similar to that of PUK (see Table 11-3).

The workup of scleritis should therefore include a complete physical examination, with attention to the joints, skin, and cardiovascular and respiratory systems. It is recommended that the ophthalmologist consult with a rheumatologist or other internist with experience in diagnosing and managing these conditions. Laboratory studies should always be guided by the history and findings of the physical examination. However, the laboratory tests listed in Table 11-5 are generally recommended as an initial screening.

Figure 11-26 Sclerokeratitis.

Table 11-5 Initial Laboratory Workup for Scleritis

MANAGEMENT

Although topical corticosteroids can be used to alleviate symptoms, the treatment of scleritis is systemic. A guideline for the treatment of patients with scleritis has been proposed by Sainz de la Maza et al and is shown in Figure 11-27. It is important to clearly define treatment goals: treatment failure may be defined as progression of disease to a more severe form (eg, nodular to necrotizing) or failure to achieve response to treatment after 2–3 weeks of therapy, in which case an alternate therapeutic strategy will need to be instituted. Idiopathic diffuse and nodular forms of scleritis, which have no ocular complications and little scleral inflammation, may be responsive to treatment with oral NSAIDs (eg, ibuprofen, indomethacin). If one NSAID is not effective, another may be tried; only one NSAID should be prescribed at a time. Systemic corticosteroid treatment may be used if the patient is unresponsive to NSAIDs or inflammation is more severe; NSAIDs and steroids should not be given simultaneously. Prednisone may be started at 1 mg/kg daily and then tapered within the first 2 weeks of treatment. Remission may be maintained with NSAIDs. Gastroprotective medication should be given to patients prescribed NSAIDs or steroids.

If corticosteroid treatment fails or the patient relapses after tapering the steroid, immunosuppression therapy may be considered. These cases often respond to antimetabolites (eg, methotrexate, azathioprine, mycophenolate mofetil). Immunosuppression treatment (eg, antimetabolites; T-cell inhibitors such as cyclosporin A or tacrolimus; alkylating agents such as cyclophosphamide) or biologic response modifiers (eg, anti-TNF-α medications such as infliximab; anti-CD20 agents such as rituximab) are usually necessary in patients with associated systemic disease, necrotizing scleritis, and/or progressive destructive ocular lesions.

Patients receiving systemic treatment must be monitored closely by a physician specially trained in the administration of these medications and in the early detection and management of their complications. In addition, they should be informed that close follow-up with the ophthalmologist and partnering providers is necessary to monitor their disease status and treatment. Antituberculosis and anti-Pneumocystis coverage may be necessary for at-risk patients. In patients whose systemic evaluation is initially negative, it is important to repeat the workup annually.

Figure 11-27 Suggested guideline for the treatment of patients with scleritis. BRM = biologic response modifier; IMT = immunomodulatory therapy; NSAIDs = nonsteroidal anti-inflammatory drugs; SAIDs = steroidal anti-inflammatory drugs; TNF = tumor necrosis factor; >2+ = grading of level of scleral inflammation (by authors of this figure). *Consider BRM such as rituximab for ovarian protection. †Consider first IMT (antimetabolite agent). If therapeutic failure, consider BRM (anti-TNF-α agent). If potentially lethal disease: alkylating agent IMT.

(Reproduced with permission from Sainz de la Maza M, Molina N, Gonzalez-Gonzalez LA, Doctor PP, Tauber J, Foster CS. Scleritis therapy. Ophthalmology. 2012;119(1):57.)

Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A, Van Gelder RN. 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.

Ragam A, Kolomeyer AM, Fang C, Xu Y, Chu DS. Treatment of chronic, noninfectious, non-necrotizing scleritis with tumor necrosis factor alpha inhibitors. Ocul Immunol Inflamm. 2014;22(6):469–477.

Sainz de la Maza M, Molina N, Gonzalez-Gonzalez LA, Doctor PP, Tauber J, Foster CS. Scleritis therapy. Ophthalmology. 2012;119(1):51–58.

Singh J, Sallam A, Lightman S, Taylor S. Episcleritis and scleritis in rheumatic disease. Curr Rheumatol Rev. 2011;7(1):15–23.

Watson PG, Young RD. Scleral structure, organization and disease: a review. Exp Eye Res. 2004; 78(3):609–623.

Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.