Page 1039 - Clinical Immunology_ Principles and Practice ( PDFDrive )

1002 Part seven Organ-Specific Inflammatory Disease

of prednisone, cyclosporine, and azathioprine may be used. malignancy, ocular metastatic tumor spread and the effects of
Despite the critical influence of donor–recipient histocompat- drugs, including chemotherapy agents, must be excluded before
ibility matching for solid organ transplant survival, the chance CAR is diagnosed.
of corneal graft survival is not significantly improved by HLA The natural history of CAR is one of progressive visual loss,
matching. although this occurs over a variable period. Corticosteroid and
Corneal transplantation has traditionally been accomplished other immunosuppressive drugs have been successfully used to
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by penetrating keratoplasty, in which all layers of the cornea are treat the ocular disease. It is suggested that serum antibody
simultaneously replaced. Many centers are increasingly performing levels can be monitored to guide therapy. In some cases, advanced
lamellar keratoplasty, in which layers of the cornea, such as the photoreceptor damage can be irreversible despite therapy.
endothelium and Descemet membrane, are selectively trans-
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planted. Descemet membrane endothelial keratoplasty (DMEK) IMMUNOLOGIC ETIOLOGIC FACTORS IN
is an example of endothelial keratoplasty. Although technically “NONIMMUNOLOGIC” OCULAR DISEASE
more challenging, lamellar keratoplasty results in faster visual
recovery and a reduced likelihood of transplant rejection. Age-related macular degeneration (ARMD) is the leading cause
of irreversible visual loss in older persons in Western nations.
CANCER-ASSOCIATED RETINOPATHY A spectrum of pathologies can occur at the macula, ranging
from relatively benign lipid deposits, called drusen, to the
Cancer-associated retinopathy (CAR) is a rare paraneoplastic sometimes visually devastating retinal pigment epithelium atrophy
syndrome that is most commonly associated with small cell or subretinal/choroidalneovascular membranes. The pathogenic
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carcinoma of the lung. In addition, the disease has been docu- stimulus for these age-related changes is unknown. Genetic
mented in association with various tumors of the female polymorphisms of the complement regulatory protein, comple-
reproductive tract, carcinoma of the breast, and neuroendocrine ment factor H, influences the susceptibility to ARMD, suggesting
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bronchial carcinoma. For 50% of patients, CAR is the presenting that this disease is related to chronic inflammation. Subretinal
feature of their malignancy. Interestingly, there are now reports scar tissue removed from patients with advanced, neovascular
of retinopathy mimicking CAR but occurring in an apparently disease may contain immunoglobulins and complement com-
healthy individual. Melanoma-associated retinopathy is a related ponents. The histopathology of ARMD includes inflammatory
syndrome, occurring in patients with metastatic cutaneous cells, including lymphocyte subsets, and local cell populations
melanoma. can express class II MHC antigens. Inhibition of complement
Histopathological examinations of postmortem specimens activation is under study to treat or prevent ARMD.
taken from patients with CAR consistently demonstrate loss of
inner and outer segments of the retinal photoreceptors. This Please check your eBook at https://expertconsult.inkling.com/
destruction was initially attributed to the release of a hormone-like for self-assessment questions. See inside cover for registration
substance by malignant cells, but evidence has now accumulated details.
in support of an autoimmune etiology. Affected individuals
produce antibodies against one or more retinal photoreceptor
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antigens. These antibodies induce experimental CAR when REFERENCES
injected into laboratory animals. Although more than 15 antigens
have been described in relation to CAR, the most common is 1. Stuart PM, Griffith TS, Usui N, et al. CD95 ligand (FasL)-induced
apoptosis is necessary for corneal allograft survival. J Clin Invest
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has been identified as recoverin, a photoreceptor protein that 2. Wang S, Boonman ZF, Li HC, et al. Role of TRAIL and IFN-gamma in
participates in visual adaptation. Experimental work supports CD4+ cell-dependent tumor rejection in the anterior chamber of the eye.
the hypothesis that a single mutational event simultaneously J Immunol 2003;171:2789–96.
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of a tumor that encodes CAR antigen and stimulates formation aqueous humor. Invest Ophthalmol Vis Sci 1991;32:2201–11.
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Med 2007;13:711–18.
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CAR generally occurs after the age of 60 years. Patients usually experimental autoimmune uveitis. J Immunol 2009;182:3183–90.
complain of decreased vision, although other symptoms may 6. Kennedy MC, Rosenbaum JT, Brown J, et al. Novel production of
include transient visual obscurations, night blindness, scoto- interleukin-1 receptor antagonist peptides in normal human cornea. J
mata, glare, and photosensitivity. Although visual acuity can Clin Invest 1995;95:82–8.
be dramatically reduced, other clinical signs are often subtle. 7. Taylor AW, Kaplan HJ. Ocular immune privilege in the year 2010:
An afferent pupillary defect can be present if the retinopathy is ocular immune privilege and uveitis. Ocul Immunol Inflamm
asymmetrical. There may be mild iridocyclitis and/or anterior 2010;18:488–92.
vitritis, narrowing of retinal arterioles, mottling of retinal pigment 8. Sohn JH, Bora PS, Suk HJ, et al. Tolerance is dependent on complement
epithelium, and optic disc pallor. Visual field abnormalities occur. C3 fragment iC3b binding to antigen-presenting cells. Nat Med
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Electroretinography shows either reduced or completely flattened 9. Dullforce PA, Garman KL, Seitz GW, et al. APCs in the anterior uveal
amplitudes. The disease must be differentiated from optic neuritis tract do not migrate to draining lymph nodes. J Immunol
which, unlike CAR, typically occurs in younger persons, some 2004;172:6701–8.
of whom suffer from MS, and is painful. In contrast to CAR, 10. Willcox MD. Characterization of the normal microbiota of the ocular
optic neuritis typically has an abrupt onset. In patients with surface. Exp Eye Res 2013;117:99–105.