largely involves IgA produced by the lacrimal gland, and cellular immunity is dominated by CD4+ T cells. Serosal mast cells, which contain neutral proteases, are normally present in the conjunctiva, and the number of mucosal mast cells with granules containing only tryptase is increased in the conjunctiva of atopic patients. Mast-cell degranulation produces conjunctival redness, chemosis, mucus discharge, and itching.

Cornea

The normal cornea can have neither an acute allergic reaction (as it contains no mast cells) nor a typical Arthus reaction (as there are no blood vessels). However, the cornea does participate in immune reactions by way of humoral and cellular immune elements that enter the periphery from the limbal blood vessels. These anatomical features may explain why so many immune-mediated disorders of the cornea occur primarily in the corneal periphery and limbus. Alternatively, ingress of leukocytes through the ciliary body and iris root and ingress of plasma proteins through breakdown of the blood–ocular barrier (as occurs in uveitis syndromes) are other means by which immune effectors gain access to the cornea.

The cornea can act as an immunologic blotter, soaking up antigens from the ocular surface. This phenomenon was first described by Wessely in 1911, when foreign antigen was injected into the cornea of a previously sensitized animal and a ring-shaped infiltrate formed in the corneal stroma concentric to the injection site, much like an antigen-antibody complex in an immunodiffusion test. Still called a Wessely immune ring, this infiltrate contains complement factors and/or neutrophils. Circulating antibodies are not required if sufficient local antibody production is stimulated by antigens deposited in the cornea. The antigen may be a drug, as in the peripheral corneal infiltrates associated with a neomycin reaction; a foreign body; or an unknown substance, as in the corneal infiltrates that can occur in contact lens wearers. Wessely rings may persist for some time in corneas traumatized by a foreign body, even after the foreign body is removed.

Sclera

Nearly 50% of patients with necrotizing scleritis have an associated systemic immunologic or connective tissue disease. Immune-complex deposition, granulomatous inflammation, and occlusive vasculitis have been implicated in the pathogenesis of scleral inflammation.

Diagnostic Approach to Immune-Mediated Ocular Disorders

Many, but not all, immune-mediated ocular disorders are secondary to a systemic disease. As with most medical problems, diagnostic investigations need to begin with a complete history, including a review of systems, and a general physical examination, as indicated. Some of the more common laboratory diagnostic tests that are selected to further narrow the differential diagnosis are listed in Table 6-2. In general, except in the case of rheumatoid arthritis, which has a strong predilection for scleral and corneal involvement, the workup for patients with immune-mediated corneal disease in whom an underlying disease is suspected is quite similar to that for the uveitis patient. In a patient presenting with ocular inflammation, diagnosing systemic vasculitis with tests, including antineutrophil cytoplasmic autoantibody tests (see Table 6-2), may be instrumental in instituting early life-saving therapy.

Table 6-2

See BCSC Section 9, Intraocular Inflammation and Uveitis, for more information on the diagnostic workup of patients with uveitis. Table 6-3 provides the clinical interpretation of ocular surface cytology for immune-mediated keratoconjunctivitis. Finally, it should be noted that corneal and ocular surface morbidities may result from underlying autoimmune disease. Generally, when a systemic disease is suspected, it is advisable to coordinate care with an internist or rheumatologist, especially if systemic immune suppression is being considered.

Table 6-3