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J Immunother Cancer 2019 03 4;7(1):61. Epub 2019 Mar 4.

Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Rd NW, New Research Building Suite E 501, Washington, DC, 20057, USA.

Balancing the potential for durable remissions with autoimmune-like toxicities is a key clinical challenge in the use of immune checkpoint inhibitors (ICI). Certain toxicities are associated with an increased response rate; however, the molecular underpinnings of this association are poorly understood. Here, we report a patient with wide spread uveal melanoma who had an exceptional response to treatment with ipilimumab and nivolumab, but suffered severe immune-related sequelae, including central serous retinopathy with retinal detachment, tinnitus, and vitiligo resembling Vogt-Koyanagi-Harada disease, and refractory enteritis. Read More

J Control Release 2019 02 17;296:68-80. Epub 2019 Jan 17.

Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21231, USA; Departments of Oncology, Neurosurgery, and Pharmacology & Molecular Sciences, The Johns Hopkins University, Baltimore, MD 21231, USA. Electronic address:

Noninfectious uveitis is a potentially blinding ocular condition that often requires treatment with corticosteroids to prevent inflammation-related ocular complications. Severe forms of uveitis such as panuveitis that affects the whole eye often require a combination of topical and either regional or systemic corticosteroid. Regional corticosteroids are currently delivered inside the eye by intravitreal injection (e. Read More

BMC Ophthalmol 2018 Nov 3;18(1):285. Epub 2018 Nov 3.

Department of Ophthalmology, National Referral Center for rare Ocular Diseases, Hôpital Cochin, APHP, Université Paris Descartes, Paris, France.

Background: The early diagnosis of cancer is of crucial importance and a key prognostic factor. Cancer-associated retinopathy (CAR) can be symptomatic prior to other manifestations directly related to malignant tumors. The aim of this study was to show that, in selected cases, ophthalmic findings are consistent enough with the diagnosis of CAR to trigger investigations aimed at detecting a previously unknown malignancy. Read More

Front Immunol 2017 28;8:505. Epub 2017 Apr 28.

School of Medicine, Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA.

Autoantibodies (AAbs) against glycolytic enzymes: aldolase, α-enolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in sera of patients with blinding retinal diseases, such as paraneoplastic [cancer-associated retinopathy (CAR)] and non-paraneoplastic autoimmune retinopathies, as well as in many other autoimmune diseases. CAR is a degenerative disease of the retina characterized by sudden vision loss in patients with cancer and serum anti-retinal AAbs. In this review, we discuss the widespread serum presence of anti-glycolytic enzyme AAbs and their significance in autoimmune diseases. Read More

Genome Med 2017 03 27;9(1):29. Epub 2017 Mar 27.

Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.

Background: Age-related macular degeneration (AMD) is a common condition of vision loss with disease development strongly influenced by environmental and genetic factors. Recently, 34 loci were associated with AMD at genome-wide significance. So far, little is known about a genetic overlap between AMD and other complex diseases or disease-relevant traits. Read More

JAMA Ophthalmol 2016 Oct;134(10):1184-1188

Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Importance: In recent years, the treatment of patients with advanced cutaneous melanoma has undergone substantial changes. Patients can now be offered treatment with immune checkpoint inhibitors, which are capable of increasing patient survival. However, these new treatments are associated with immune-related adverse effects that can involve different organ systems, including the eye. Read More

Exp Eye Res 2016 06 13;147:161-168. Epub 2016 May 13.

Casey Eye Institute, School of Medicine, Oregon Health & Science University, Portland, OR 97239, USA.

High titers of anti-carbonic anhydrase II (anti-CA II) autoantibodies were detected in sera of patients with autoimmune retinopathies (AR), including cancer-associated retinopathy (CAR) and also in normal population. The goal was to investigate whether unique immunodominant epitopes for anti-CAII autoantibodies occur in AR and CAR. A cohort of 216 patients with symptoms of AR and CAR and healthy controls, seropositive for anti-CA II autoantibodies were analyzed for the prevalence of CAII major domains. Read More

Curr Genomics 2013 May;14(3):166-72

Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD ; Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Epigenetics pertains to heritable alterations in gene expression that do not involve modification of the underlying genomic DNA sequence. Historically, the study of epigenetic mechanisms has focused on DNA methylation and histone modifications, but the concept of epigenetics has been more recently extended to include microRNAs as well. Epigenetic patterning is modified by environmental exposures and may be a mechanistic link between environmental risk factors and the development of disease. Read More

BMC Ophthalmol 2013 Sep 25;13:48. Epub 2013 Sep 25.

Ocular Immunology Laboratory, Oregon Health and Science University, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239, USA.

Background: Autoimmune retinopathy (AR) and Cancer-Associated Retinopathy (CAR) are associated with a diverse repertoire of anti-retinal autoantibodies (AAbs) but not all antigenic targets have been characterized. Identification of new AAbs may help with clinical diagnosis and prognosis of retinal dysfunction in AR. The goal was to identify frequently targeted retinal autoantigens within the 60-70-kDa molecular weight range. Read More

Surv Ophthalmol 2013 Sep-Oct;58(5):430-58

Jules Stein Eye Institute, UCLA, Los Angeles, CA, USA.

Paraneoplastic syndromes involving the visual system are a heterogeneous group of disorders occurring in the setting of systemic malignancy. Timely recognition of one of these entities can facilitate early detection and treatment of an unsuspected, underlying malignancy, sometimes months before it would have otherwise presented, and gives the patient an increased chance at survival. We outline the clinical features, pathogenesis, and treatment strategies for the retinal- and optic nerve-based paraneoplastic syndromes: cancer-associated retinopathy; melanoma-associated retinopathy; paraneoplastic vitelliform maculopathy; bilateral diffuse uveal melanocytic proliferation; paraneoplastic optic neuropathy; and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Read More

Mediators Inflamm 2012 29;2012:148039. Epub 2012 Aug 29.

Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

The human vitreous humour (VH) is a transparent, highly hydrated gel, which occupies the posterior segment of the eye between the lens and the retina. Physiological and pathological conditions of the retina are reflected in the protein composition of the VH, which can be sampled as part of routine surgical procedures. Historically, many studies have investigated levels of individual proteins in VH from healthy and diseased eyes. Read More

PLoS One 2012 3;7(7):e39890. Epub 2012 Jul 3.

Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.

Recent studies have suggested that some kinds of microbial infection may have a crucial role in the development of many diseases such as autoimmune diseases and certain types of cancer. It has been reported that some chronic infections, such as Chlamydia pneumoniae, and immunological dysfunctions are associated with age-related macular degeneration (AMD), a leading cause of blindness. To evaluate the association between systemic low-level inflammation induced by infection and AMD pathogenesis, we investigated whether intraperitoneal injection of lipopolysaccharide (LPS) can modulate the development of laser-induced choroidal neovascularization (CNV), a key feature of AMD. Read More

Brain 2012 Jun 28;135(Pt 6):1794-818. Epub 2012 Apr 28.

Monash Immunology and Stem Cell Laboratories, Monash University, Clayton VIC 3800, Australia.

Multiple sclerosis involves demyelination and axonal degeneration of the central nervous system. The molecular mechanisms of axonal degeneration are relatively unexplored in both multiple sclerosis and its mouse model, experimental autoimmune encephalomyelitis. We previously reported that targeting the axonal growth inhibitor, Nogo-A, may protect against neurodegeneration in experimental autoimmune encephalomyelitis; however, the mechanism by which this occurs is unclear. Read More

J Autoimmun 2009 Nov-Dec;33(3-4):247-54. Epub 2009 Oct 27.

Dobbs Ocular Immunology Laboratories, Emory Eye Center and Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Autoantibody production is associated with a variety of ocular disorders, including autoimmune retinopathy (AIR) and age-related macular degeneration (AMD). A breakdown of immunologic tolerance (ocular immune privilege), including the blood-retinal barrier, anti-immune and anti-inflammatory proteins, and anterior chamber-associated immune deviation may play important roles in these disorders. Although the exact triggers for ocular autoimmunity are unknown, autoimmune targeting of retinal tissue is clearly associated with and may contribute to the pathogenesis of both AIR and AMD. Read More

Autoimmun Rev 2009 Mar 23;8(5):410-4. Epub 2009 Jan 23.

Ocular Immunology Laboratory, Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.

Paraneoplastic retinopathies (PR), including cancer-associated retinopathy (CAR) or the closely related melanoma-associated retinopathy (MAR) occur in a small subset of patients with retinal degeneration and systemic cancer. This autoimmune syndrome is characterized by sudden, progressive loss of vision in association with circulating anti-retinal autoantibodies. The PR syndromes are heterogeneous, may produce a number of ocular symptoms, and may be associated with several different neoplasms, including lung, breast, prostate, gynecological, and colon cancer, melanoma, and hematologic malignancies. Read More

Lung Cancer 2007 Sep 29;57(3):399-403. Epub 2007 Mar 29.

Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan.

Cancer-associated retinopathy (CAR) is a rare paraneoplastic disorder that is frequently found in patients with small cell lung cancer (SCLC); it is caused by autoantibody to the 23-kDa photoreceptor protein, recoverin. We report a 9-year survivor of SCLC after concurrent chemoradiotherapy. His anti-recoverin antibody remains positive. Read More

Ann Neurol 2003 Jul;54(1):38-50

Department of Neurology, Mayo Graduate and Medical Schools, Mayo Clinic, Rochester, MN 55905, USA.

Autoantibodies have defined two paraneoplastic visual disorders related to small-cell lung carcinoma: retinopathy ("CAR"-IgG [23kDa, recoverin]) and optic neuritis collapsin response-mediated protein 5 (CRMP-5-IgG [62kDa]). Among 16 patients with CRMP-5-IgG and optic neuritis (aged 52-74 years; all smokers, 9 women), we documented coexisting retinitis in 5. None had CAR-IgG. Read More

Surv Ophthalmol 2003 Jan-Feb;48(1):12-38

Department of Internal Medicine, Division of Neurology, University of Nevada School of Medicine, Las Vegas 89102, USA.

Unusual neuro-ophthalmologic symptoms and signs that go unexplained should warrant a thorough investigation for paraneoplastic syndromes. Although these syndromes are rare, these clinical manifestations can herald an unsuspected, underlying malignancy that could be treated early and aggressively. This point underscores the importance of distinguishing and understanding the various, sometimes subtle, presentations of ocular paraneoplastic syndromes. Read More

Rev Neurol 2000 Dec 16-31;31(12):1228-36

Servicio de Anatomía Patológica, Hospital Prínceps d'Espanya, Departamento de Biología Celular y Anatomía Patológica, Universidad de Barcelona, Campus de Bellvitge, Hospitalet de Llobregat, Banco de Tejidos Neurológicos, Barcelona, España.

Introduction And Development: The paraneoplastic neurological syndromes are alterations associated with neoplasias. However, they are not caused by metastases or complications such as infections, vascular disorders, metabolic or nutritional alterations or secondary effect of treatment. The paraneoplastic syndromes are often associated with the creation of autoantibodies against antigens produced by the neoplastia, but also may be against other cells or target molecules of the patient. Read More

Br J Biomed Sci 1996 Sep;53(3):227-34

University of California, Sacramento 95816, USA.

What are the earliest indications of cancer? What prompts an apparently healthy person to suspect that 'something may be wrong'? The first manifestations may involve a growing awareness of neuronal dysfunction, such as headaches, dizziness, physical degeneration or vision abnormalities. While denial may extend the time between the patient's appreciation of the health hazard, particularly if the indications are subtle, a sudden decline in vision may be one of the most readily perceived, and provide the strongest stimulation to seek medical help. Cancer-induced neuropathies are rare but provide much information on the genesis of a defined group of autoimmune reactions, and the biological mechanisms involved. Read More

Arch Ophthalmol 1993 Jul;111(7):974-8

University of California Davis, Ophthalmology Research, Sacramento.

Objective: We have inquired into the reason why patients with cancer-associated retinopathy (CAR) produce antibody reactions with the 23-kd retinal CAR antigen. Possible reasons include the expression of this antigen in the related carcinoma. Previous studies have failed to identify any antigenic counterpart expressed by in vitro cultivated small-cell carcinoma of the lung. Read More