Chapter 16: Immunologic Diseases of the Eye
CELL-MEDIATED DISEASES
This group of diseases appears to be associated with cell-mediated immunity or delayed hypersensitivity. Various structures of the eye are invaded by mononuclear cells, principally lymphocytes and macrophages, in response to one or more chronic antigenic stimuli. In the case of chronic infections such as tuberculosis, leprosy, toxoplasmosis, and herpes simplex, the antigenic stimulus has clearly been identified as an infectious agent in the ocular tissue. Such infections are often associated with delayed skin test reactivity following the intradermal injection of an extract of the organism.
More intriguing but less well understood are the granulomatous diseases of the eye for which no infectious cause has been found. Such diseases are thought to represent cell-mediated, possibly autoimmune processes, but their origin remains obscure.
OCULAR SARCOIDOSIS
Ocular sarcoidosis is characterized by a panuveitis with occasional inflammatory involvement of the optic nerve and retinal blood vessels (see Chapter 7).
Immunologic Pathogenesis
Although many infectious or allergic causes of sarcoidosis have been suggested, none has been confirmed. Noncaseating granulomas are seen in the uvea, optic nerve, and adnexal structures of the eye as well as elsewhere in the body. The presence of macrophages and giant cells suggests that particulate matter is being phagocytosed, but this material has not been identified.
Patients with sarcoidosis are usually anergic to extracts of the common microbial antigens such as those of mumps, Trichophyton, Candida, and Mycobacterium tuberculosis. As in other lymphoproliferative disorders such as Hodgkin's disease and chronic lymphocytic leukemia, this may represent suppression of T cell activity such that the normal delayed hypersensitivity responses to common antigens cannot take place. Meanwhile, circulating immunoglobulins are usually detectable in the serum at higher than normal levels.
Immunologic Diagnosis
The diagnosis is largely inferential. Negative skin tests to a battery of antigens to which the patient is known to have been exposed are highly suggestive, and the same is true of the elevation of serum immunoglobulins. Biopsy of a conjunctival nodule or scalene lymph node may provide positive histologic evidence of the disease. X-rays of the chest reveal hilar adenopathy in many cases. Elevated levels of serum lysozyme, serum angiotensin-converting enzyme, or serum calcium may be detected.
Treatment
See Chapter 15.
SYMPATHETIC OPHTHALMIA & VOGT-KOYANAGI-HARADA SYNDROME
These two disorders are discussed together because they have certain common clinical features. Both are thought to represent autoimmune phenomena affecting pigmented structures of the eye and skin, and both may give rise to meningeal symptoms.
Clinical Features
Sympathetic ophthalmia is an inflammation in the second eye after the other has been damaged by penetrating injury. In most cases, some portion of the uvea of the injured eye has been exposed to the atmosphere for at least 1 hour. The uninjured or "sympathizing" eye develops minor signs of anterior uveitis after a period ranging from 2 weeks to many years. However, the vast majority of cases occur within 1 year. Floating spots and loss of the power of accommodation are among the earliest symptoms. The disease may progress to severe iridocyclitis with pain and photophobia. Usually, however, the eye remains relatively quiet and painless while the inflammatory disease spreads around the entire uvea. Despite the presence of panuveitis, the retina usually remains uninvolved except for perivascular cuffing of the retinal vessels with inflammatory cells. Optic nerve swelling and secondary glaucoma may occur. The disease may be accompanied by vitiligo (patchy depigmentation of the skin) and poliosis (whitening) of the eyelashes. For unknown reasons, the incidence of this disease has decreased markedly over the last several decades.
Vogt-Koyanagi-Harada syndrome consists of inflammation of the uvea of one or both eyes characterized by acute iridocyclitis, patchy choroiditis, and serous detachment of the retina (see Chapter 15). It usually begins with an acute febrile episode with headache, dysacusis, and occasionally vertigo. Patchy loss or whitening of scalp hair is described in the first few months of the disease. Vitiligo and poliosis are commonly present but are not essential for the diagnosis. Although the initial iridocyclitis may subside quickly, the course of the posterior disease is often indolent, with long-standing serous detachment of the retina and significant visual impairment.
Immunologic Pathogenesis
In both sympathetic ophthalmia and Vogt-Koya-nagi-Harada syndrome, delayed hypersensitivity to melanin-containing structures is thought to occur. Although a viral cause has been suggested for both of these disorders, there is no convincing evidence of an infectious origin. It is postulated that some insult, infectious or otherwise, alters the pigmented structures of the eye, skin, and hair in such a way as to provoke delayed hypersensitivity responses to them. Soluble materials from the outer segments of the photoreceptor layer of the retina (retinal S-antigens) have been incriminated as possible autoantigens. Patients with Vogt-Koyanagi-Harada syndrome are usually Orientals, which suggests an immunogenetic predisposition to the disease.
Histologic sections of the traumatized eye from a patient with sympathetic ophthalmia may show uniform infiltration of most of the uvea by lymphocytes, epithelioid cells, and giant cells. The overlying retina is characteristically intact, but nests of epithelioid cells may protrude through the pigment epithelium of the retina, giving rise to Dalen-Fuchs nodules. The inflammation may destroy the architecture of the entire uvea, leaving an atrophic, shrunken globe.
Immunologic Diagnosis
Skin tests with soluble extracts of human or bovine uveal tissue are said to elicit delayed hypersensitivity responses in these patients. Several investigators have shown that cultured lymphocytes from patients with these two diseases undergo transformation to lymphoblasts in vitro when extracts of uvea or rod outer segments are added to the culture medium. Circulating antibodies to uveal antigens have been found in patients with these diseases, but such antibodies are to be found in any patient with long-standing uveitis, including those suffering from several infectious entities. The spinal fluid of patients with Vogt-Koyanagi-Harada syndrome may show increased numbers of mononuclear cells and elevated protein in the early stages. Treatment of both conditions requires at least systemic steroids and often oral immunosuppressive therapy.
OTHER DISEASES OF CELL-MEDIATED IMMUNITY
Giant cell arteritis (temporal arteritis) (see Chapter 15) may have disastrous effects on the eye, particularly in elderly individuals. The condition is manifested by temporal arteritis and polymyalgia rheumatica. Ocular complications include anterior ischemic optic neuropathy and central retinal artery occlusion. Such patients have an elevated sedimentation rate. Biopsy of the temporal artery reveals extensive infiltration of the vessel wall with giant cells and mononuclear cells.
Polyarteritis nodosa (see Chapter 15) is a vasculitis which predominantly affects small to medium-sized vessels. It can affect both the anterior and posterior segments of the eye. The corneas of such patients may show peripheral thinning and cellular infiltration. The retinal vessels reveal extensive necrotizing inflammation characterized by eosinophil, plasma cell, and lymphocyte infiltration.
Behçet's disease (see Chapter 15) has an uncertain place in the classification of immunologic disorders. It is characterized by recurrent iridocyclitis with hypopyon and occlusive vasculitis of the retinal vessels. Although it has many of the features of a delayed hypersensitivity disease, dramatic alterations of serum complement levels at the very beginning of an attack suggest an immune complex disorder. Furthermore, high levels of circulating immune complexes have recently been detected in patients with this disease. Most patients with eye symptoms are positive for HLA-B51, a subtype of HLA-B5.
Contact dermatitis of the eyelids represents a significant though minor disease caused by delayed hypersensitivity. Atropine, perfumed cosmetics, materials contained in plastic spectacle frames, and other locally applied agents may act as the sensitizing hapten. The lower lid is more extensively involved than the upper lid when the sensitizing agent is applied in drop form. Periorbital involvement with erythematous, vesicular, pruritic lesions of the skin is characteristic.
Phlyctenular keratoconjunctivitis (Figure 16-8) represents a delayed hypersensitivity response to certain microbial antigens, principally those of M tuberculosis and Staphylococcus aureus (see Chapters 5 and 6).
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10.1036/1535-8860.ch16