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Chapter 16: Immunologic Diseases of the Eye
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Immunologic Diseases of the Eye
Ocular manifestations are a common feature of immunologic diseases even though, paradoxically, the eye is also a site of immune privilege. The propensity for immunologic disease to affect the eye derives from a number of factors, including the highly vascular nature of the uvea, the tendency for immune complexes to be deposited in various ocular tissues, and the exposure of the mucous membrane of the conjunctiva to environmental allergens. Inflammatory eye disorders are more obvious (and often more painful) than those of other organs such as the thyroid or the kidney.
Immunologic diseases of the eye can be grossly divided into two major categories: antibody-mediated and cell-mediated diseases. As is the case in other organs, there is ample opportunity for the interaction of these two systems in the eye.
ANTIBODY-DEPENDENT & ANTIBODY-MEDIATED DISEASES
Before it can be concluded that a disease of the eye is antibody-dependent, the following criteria must be satisfied:
There must be evidence of specific antibody in the patient's serum or plasma cells.
The antigen must be identified and, if feasible, characterized.
The same antigen must be shown to produce an immunologic response in the eye of an experimental animal, and the pathologic changes produced in the experimental animal must be similar to those observed in the human disease.
It must be possible to produce similar lesions in animals passively sensitized with serum from an affected animal upon challenge with the specific antigen.
Unless all of the above criteria are satisfied, the disease may be thought of as possibly antibody-dependent. In such circumstances, the disease can be regarded as antibody-mediated if only one of the following criteria is met:
If antibody to an antigen is present in higher quantities in the ocular fluids than in the serum (after adjustments have been made for the total amounts of immunoglobulins in each fluid).
If abnormal accumulations of plasma cells are present in the ocular lesion.
If abnormal accumulations of immunoglobulins are present at the site of the disease.
If complement is fixed by immunoglobulins at the site of the disease.
If an accumulation of eosinophils is present at the site of the disease.
If the ocular disease is associated with an inflammatory disease elsewhere in the body for which antibody dependency has been proved or strongly suggested.
HAY FEVER CONJUNCTIVITIS (See Also Chapter 5.)
This disease is characterized by edema and hyperemia of the conjunctiva and lids (Figure 16-1) and by itching, which is always present, and watering of the eyes. There is often an associated itching sensation in the nose as well as rhinorrhea. The conjunctiva appears pale and boggy because of the intense edema, which is often rapid in onset. There is a distinct seasonal incidence, some patients being able to establish the onset of their symptoms at precisely the same time each year. These times usually correspond to the release of pollens by specific grasses, trees, or weeds.
Immunologic Pathogenesis
Hay fever conjunctivitis is one of the few inflammatory eye disorders for which antibody dependence has been definitely established. It is recognized as a form of atopic disease with an implied hereditary susceptibility. IgE (reaginic antibody) is attached to mast cells lying beneath the conjunctival epithelium. Contact of the offending antigen with IgE triggers the release of vasoactive substances, principally leuko-trienes and histamine, in this area, and this in turn results in vasodilation and chemosis.
The role of circulating antibody to ragweed pollen in the pathogenesis of hay fever conjunctivitis has been demonstrated by passively transferring serum from a hypersensitive person to a nonsensitive one. When exposed to the offending pollen, the previously nonsensitive individual reacted with the typical signs of hay fever conjunctivitis.
Immunologic Diagnosis
Victims of hay fever conjunctivitis show many eosinophils in Giemsa-stained scrapings of conjunctival epithelium, and this is the test most commonly used to confirm the diagnosis. They show the immediate type of response, with wheal and flare, when tested by scratch tests of the skin with extracts of pollen or other offending antigens. Biopsies of the skin test sites have occasionally shown the full-blown picture of an Arthus reaction, with deposition of immune complexes in the walls of the dermal vessels. Passive cutaneous anaphylaxis can also be used to demonstrate the presence of circulating antibody.
Immunologic Treatment
Immunotherapy with gradually increasing doses of subcutaneously injected pollen extracts or other suspected allergens appears to reduce the severity of the disease in some individuals if started well in advance of the season. The mechanism is presumed to be production of blocking antibodies in response to the injection of small, graded doses of the antigen. This procedure cannot be recommended routinely, however, in view of the generally good results and relatively few complications of antihistamine therapy. Acute anaphylactoid reactions have occasionally resulted from overzealous immunotherapy. Topical antihistamines are the mainstay of treatment, and occasionally mast cell stabilizers and mild nonpenetrating corticosteroids.
Other forms of treatment are discussed in Chapter 5.
VERNAL CONJUNCTIVITIS & ATOPIC KERATOCONJUNCTIVITIS (See Also Chapter 5.)
These two diseases also belong to the group of atopic disorders. Both are characterized by itching and lacrimation of the eyes but are more chronic than hay fever conjunctivitis. Furthermore, both ultimately result in structural modifications of the lids and conjunctiva, especially atopic keratoconjunctivitis.
Vernal conjunctivitis characteristically affects children and adolescents; the incidence decreases sharply after the second decade of life. Like hay fever conjunctivitis, vernal conjunctivitis occurs only in the warm months of the year. Most of its victims live in hot, dry climates. The disease characteristically produces giant ("cobblestone") papillae of the tarsal conjunctiva (Figure 16-2). The keratinized epithelium from these papillae may abrade the underlying cornea, giving rise to complaints of foreign body sensation or even producing frank epithelial loss ("shield ulcer").
Atopic keratoconjunctivitis affects individuals of all ages and has no specific seasonal incidence. The skin of the lids has a characteristic dry, scaly appearance. The conjunctiva is pale and boggy. Both the conjunctiva and the cornea may develop scarring in the later stages of the disease. Atopic cataract has also been described. Staphylococcal blepharitis, manifested by scales and crusts on the lids, commonly complicates this disease. These patients are also more prone to herpes simplex ocular infections.
Although vernal and atopic disease may lie along a disease spectrum, often the two disorders can be differentiated. Atopic disease tends to occur in older patients, and there is little or no seasonal exacerbation. The papillae in atopic disease are smaller than in vernal disease and are as often found on the lower palpebral conjunctiva as the upper. Furthermore, corneal vascularization and conjunctival scarring are much more common in atopic disease. Finally, in atopic disease eosinophils on smears are less numerous and less often degranulated.
Immunologic Pathogenesis
Reaginic antibody (IgE) is fixed to subepithelial mast cells in both of these conditions. Contact between the offending antigen and IgE is thought to trigger degranulation of the mast cell, which in turn allows for the release of vasoactive amines in the tissues. It is unlikely, however, that antibody action alone is responsible, since-at least in the case of papillae of vernal conjunctivitis-there is heavy papillary infiltration by mononuclear cells. Hay fever and asthma occur much more frequently in patients with vernal conjunctivitis and atopic keratoconjunctivitis than in the general population. Of the criteria outlined above for demonstration of possibly antibody-dependent diseases, (2), (5), and (6) have been met by atopic keratoconjunctivitis.
Immunologic Diagnosis
Patients with atopic keratoconjunctivitis and vernal conjunctivitis generally show large numbers of eosinophils in conjunctival scrapings. Skin testing with food extracts, pollens, and various other antigens reveals a wheal-and-flare type of reaction within 1 hour after testing, but the significance of these reactions is not established. Furthermore, the exact identification of the inciting antigens in these cases is usually unknown.
Immunologic Treatment
Avoidance of allergens (if known) is helpful; such objects as duck feathers, animal danders, and certain food proteins (egg albumin and others) are possible offenders. Specific allergens have been especially difficult to demonstrate in the case of vernal disease, though some workers feel that such substances as rye grass pollens may play a causative role. Installation of air conditioning in the home or relocation to a cool, moist climate is useful in vernal conjunctivitis.
Other treatments are discussed in Chapter 5.
JOINT DISEASES AFFECTING THE EYE
The diseases in this category vary greatly in their clinical manifestations depending upon the specific disease entity and the age of the patient. Uveitis and scleritis (Chapter 7) are the principal ocular manifestations associated with joint diseases. Juvenile rheumatoid arthritis affects females more frequently than males and is commonly accompanied by iridocyclitis of one or both eyes (see Chapter 17).
Ankylosing spondylitis affects males more frequently than females, and the onset is in the second to sixth decades. It may be accompanied by iridocyclitis of acute onset, often with fibrin in the anterior chamber (Figure 16-3).
Reiter's disease affects men more frequently than women. The first attack of ocular inflammation usually consists of a self-limited papillary conjunctivitis. It follows, at a highly variable interval, the onset of nonspecific urethritis and the appearance of inflammation in one or more of the weight-bearing joints. Subsequent attacks of ocular inflammation may consist of acute iridocyclitis of one or both eyes, occasionally with hypopyon (Figure 16-4). Rheumatoid arthritis of adult onset may be accompanied by acute scleritis or episcleritis but very rarely by uveitis (Figure 16-5). (See also Chapter 7.)
Immunologic Pathogenesis
Rheumatoid factor, an IgM autoantibody directed against the patient's own IgG, may play a major role in the pathogenesis of rheumatoid arthritis. The union of IgM antibody with IgG is followed by fixation of complement at the tissue site and the attraction of leukocytes and platelets to this area. An occlusive vasculitis, resulting from this chain of events, is thought to be the cause of rheumatoid nodule formation in the sclera as well as elsewhere in the body. The occlusion of vessels supplying nutrients to the sclera is thought to be responsible for the "melting away" of the scleral collagen that is so characteristic of rheumatoid arthritis (Figure 16-6).
While this explanation may suffice for rheumatoid arthritis, patients with the ocular complications of juvenile rheumatoid arthritis, ankylosing spondylitis, and Reiter's syndrome usually have negative tests for rheumatoid factor, so other explanations must be sought.
Outside the eyeball itself, the lacrimal gland has been shown to be under attack by circulating antibodies. Destruction of acinar cells within the gland and invasion of the lacrimal gland (as well as the salivary glands) by mononuclear cells result in decreased tear secretion. The combination of dry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia), and rheumatoid arthritis is known as Sjögren's syndrome (see Chapter 15).
A growing body of evidence indicates that the immunogenetic background of certain patients accounts for the expression of their ocular inflammatory disease in specific ways. Analysis of the histocompatibility leukocyte antigen (HLA) antigen system shows that the incidence of HLA-B27 is significantly greater in patients with ankylosing spondylitis and Reiter's syndrome than could be expected by chance alone. It is not known how this antigen controls specific inflammatory responses. Other well-established HLA disease associations include HLA-A11 in sympathetic ophthalmia, HLA-A29 in birdshot choroidopathy, HLA-B51 in Behçet's syndrome, and HLA-B7 in macular histoplasmosis.
Immunologic Diagnosis
Rheumatoid factor can be detected in the serum by a number of standard tests involving the agglutination of IgG-coated erythrocytes or latex particles. Unfortunately, the test for rheumatoid factor is not positive in the majority of isolated rheumatoid afflictions of the eye.
The HLA types of individuals suspected of having ankylosing spondylitis and related diseases can be determined. HLA-B27 is associated with ankylosing spondylitis and Reiter's syndrome. X-ray of the sacroiliac area is a valuable screening procedure that may show evidence of spondylitis prior to the onset of low back pain in patients with the characteristic form of iridocyclitis.
OTHER ANTIBODY-MEDIATED EYE DISEASES (See Also Chapter 15.)
The following antibody-mediated diseases are infrequently encountered by the practicing ophthalmologist.
Systemic lupus erythematosus, associated with the presence of circulating antibodies to DNA, produces an occlusive vasculitis of the nerve fiber layer of the retina. Such infarcts result in retinal cotton-wool spots (Figure 16-7).
Pemphigus vulgaris produces painful intraepithelial bullae of the conjunctiva. It is associated with the presence of circulating antibodies to an intercellular antigen located between the deeper cells of the conjunctival epithelium.
Cicatricial pemphigoid is characterized by subepithelial bullae of the conjunctiva. In the chronic stages of this disease, cicatricial contraction of the conjunctiva may result in severe scarring of the cornea, dryness of the eyes, and ultimate blindness. Pemphigoid is associated with local deposits of tissue antibodies directed against one or more antigens located in the basement membrane of the epithelium. Immunosuppressive treatment is often needed in the progressive stages of this disease.
Lens-induced uveitis is a rare condition that may be associated with circulating antibodies to lens proteins. It is seen in individuals whose lens capsules have become permeable to these proteins as a result of trauma or other disease (see Chapter 7). Interest in this field dates back to Uhlenhuth (1903), who first demonstrated the organ-specific nature of antibodies to the lens. Witmer showed in 1962 that antibody to lens tissue may be produced by lymphoid cells of the ciliary body.
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).
CORNEAL GRAFT REACTIONS (
Figure 16-9)
Blindness due to opacity or distortion of the central portion of the cornea is a remediable disease. If all other structures of the eye are intact, a patient whose vision is impaired solely by corneal opacity can expect great improvement from a graft of clear cornea into the diseased area (see Chapter 6). Trauma, including chemical burns, is one of the most common causes of central corneal opacity. Others include scars from herpetic keratitis, endothelial cell dysfunction with chronic corneal edema (including pseudophakic bullous keratopathy and Fuchs's dystrophy), keratoconus, and opacities from previous graft failures. All of these conditions represent indications for penetrating corneal grafts, provided the patient's eye is no longer inflamed and the opacity has been allowed maximal time to undergo spontaneous resolution (usually 6-12 months). It is estimated that approximately 10,000 corneal grafts are performed in the USA annually. Of these, about 90% can be expected to produce a beneficial result.
The cornea was one of the first human tissues to be successfully grafted. The fact that recipients of corneal grafts generally tolerate them well can be attributed to (1) the absence of blood vessels or lymphatics in the normal cornea, (2) the lack of presensitization to tissue-specific antigens in most recipients, and (3) anterior chamber acquired immune deviation (ACAID). This is a series of unique immunologic properties of the anterior chamber, conferring on the graft area the status of immune privilege. Reactions to corneal grafts do occur, however, particularly in individuals whose own corneas have been damaged by previous inflammatory disease. Such corneas may have developed both lymphatics and blood vessels, providing afferent and efferent channels for immunologic reactions in the engrafted cornea.
Although attempts have been made to transplant corneas from other species into human eyes (xenografts), particularly in countries where human material is not available for religious reasons, most corneal grafts have been taken from human eyes (allografts). Except in the case of identical twins, such grafts always represent the implantation of foreign tissue into a donor site; thus, the chance for a graft rejection due to an immune response to foreign antigens is virtually always present.
The cornea is a three-layered structure composed of a surface epithelium, an oligocellular collagenous stroma, and a single-layered endothelium. Although the surface epithelium may be sloughed and later replaced by the recipient's epithelium, certain elements of the stroma and all of the donor's endothelium remain in place for the rest of the patient's life. This has been firmly established by sex chromosome markers in corneal cells when donor and recipient were of opposite sexes. The endothelium must remain healthy in order for the cornea to remain transparent, and an energy-dependent pump mechanism is required to keep the cornea from swelling with water. Since the recipient's endothelium is in most cases diseased, the central corneal endothelium must be replaced by healthy donor tissue.
A number of foreign elements exist in corneal grafts that might stimulate the immune system of the host to reject this tissue. In addition to those mentioned above, the corneal stroma is regularly perfused with IgG and serum albumin from the donor, although none of the other blood proteins are present-or only small amounts. While these serum proteins of donor origin rapidly diffuse into the recipient stroma and are thus removed from the graft site, they are theoretically immunogenic.
HLA incompatibility between donor and recipient has been shown by several authors to be significant in determining graft survival, particularly when the corneal bed is vascularized. It is known that most cells of the body possess these HLA antigens, including the endothelial cells of the corneal graft as well as certain stromal cells (keratocytes). The epithelium has been shown to possess a non-HLA antigen that diffuses into the anterior third of the stroma. Thus, while much foreign antigen may be eliminated by purposeful removal of the epithelium at the time of grafting, that amount of antigen which has already diffused into the stroma is automatically carried over into the recipient.
Despite numerous analytic studies supporting the role of HLA incompatibility in corneal graft rejection, a recent multicenter clinical trial found no use in HLA typing high risk grafts. In this study, ABO blood typing did provide a slight protective effect in high-risk cases. These surprising findings are leading many investigators to restudy the role of major and minor antigens in corneal graft rejection.
Both humoral and cellular mechanisms have been implicated in corneal graft reactions. It is likely that early graft rejections (2-4 weeks from surgery) are cell-mediated reactions. Cytotoxic lymphocytes have been found in the limbal area and stroma of affected individuals, and phase microscopy in vivo has revealed an actual attack on the grafted endothelial cells by these lymphocytes. Such lymphocytes generally move inward from the periphery of the cornea, making what is known as a "rejection line" as they move centrally. The donor cornea becomes edematous as the endothelium becomes compromised by an accumulation of lymphoid cells.
Late rejection of a corneal graft may occur several weeks to many months after implantation of donor tissue into the recipient eye. Such reactions may be antibody-mediated, since cytotoxic antibodies have been isolated from the serum of patients with a history of multiple graft reactions in vascularized corneal beds. These antibody reactions are complement- dependent and attract polymorphonuclear leukocytes, which may form dense rings in the cornea at the sites of maximum deposition of immune complexes. In experimental animals, similar reactions have been produced by corneal xenografts, but the intensity of the reaction can be markedly reduced either by decomplementing the animal or by reducing its leukocyte population through mechlorethamine therapy.
Treatment
The mainstay of the treatment of corneal graft reactions is corticosteroid therapy. This medication is generally given in the form of frequently applied eye drops (eg, 1% prednisolone acetate every hour) until the clinical signs abate. These clinical signs consist of conjunctival hyperemia in the perilimbal region, a cloudy cornea, cells and protein in the anterior chamber, and keratic precipitates on the corneal endothelium. The earlier treatment is applied, the more effective it is likely to be. Some cases may require systemic or periocular corticosteroids in addition to local eye drop therapy. High-dose intravenous steroids may also be efficacious if used sooner than 8 days after onset of the rejection period. Occasionally, vascularization and opacification of the cornea occur so rapidly as to make corticosteroid therapy useless, but even the most hopeless-appearing graft reactions have occasionally been reversed by corticosteroid therapy. Oral cyclosporine has been used successfully in the treatment of corneal graft rejection, and some benefit may be derived from cyclosporine eye drops.
Patients known to have rejected many previous corneal grafts are managed somewhat differently, particularly if disease affects their only remaining eye. Some surgeons may choose to find a close HLA match between donor and recipient, but conflicting analytic studies make doing so of questionable use. Pretreatment of the recipient with immunosuppressive agents such as azathioprine has also been resorted to in some cases.
REFERENCESList of Figures
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Figure 16-1: Hay fever conjunctivitis. Note edema and hyperemia of the conjunctiva. (Courtesy of M Allansmith and B McClellan.) |
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Figure 16-2: Giant papillae ("cobblestones") in the tarsal conjunctiva of a patient with vernal conjunctivitis. |
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Figure 16-3: Acute iridocyclitis in a patient with ankylosing spondylitis. Note fibrin clot in anterior chamber. |
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Figure 16-4: Acute iridocyclitis with hypopyon in a patient with Reiter's disease. |
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Figure 16-5: Scleral nodules in a patient with rheumatoid arthritis. (Courtesy of S Kimura.) |
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Figure 16-6: Scleral thinning in a patient with rheumatoid arthritis. Note dark color of the underlying uvea. |
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Figure 16-7: Cotton-wool spots in the retina of a patient with systemic lupus erythematosus. |
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Figure 16-8: Phlyctenule (arrow) at the margin of the cornea. (Courtesy of P Thygeson.) |
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Figure 16-9: A cornea severely scarred by chronic atopic keratoconjunctivitis into which a central graft of clear cornea has been placed. Note how distinctly the iris landmarks are seen through the transparent graft. (Reproduced, with permission, from Stites DP, Terr AI [editors]: Basic & Clinical Immunology, 7th ed. Appleton & Lange, 1991.) |
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10.1036/1535-8860.ch16