Cancer associated retinopathy (CAR): An autoimmune-mediated paraneoplastic syndrome

Cancer associated retinopathy (CAR) is an uncommon paraneoplastic retinopathy in which antibodies are directed against retinal antigens. Vision loss is associated with abnormal ERG findings. Few case reports and lack of controlled clinical trials make management of this syndrome especially challenging for the clinician. Herein, we describe the clinical, histopathologic and electrophysiologic features of CAR, along with a summary of previously employed management options. Cancer associated retinopathy syndrome has been recognized as a paraneoplastic disorder, most commonly associated with small cell lung cancer, in which cross-reacting autoantibodies against retinal antigen cause retinal dysfunction. Bilateral vision loss as a result of both rod and cone dysfunction in CAR may occur over a period of months, and visual symptoms may precede diagnosis of the systemic malignancy. The heterogeneity in antigens that have been identified as targets of antibody-mediated retinal damage perhaps help to explain the complexity of symptoms and the treatment challenges posed by patients with CAR.     

Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy

Background  

Autoimmune retinal degeneration may occur in patients who present with sudden or, less commonly, subacute loss of vision of retinal origin, associated with an abnormal ERG, through the action of autoantibodies against retinal proteins. Often the patients are initially diagnosed with or suspected of having a paraneoplastic retinopathy (PR), such as cancer-associated retinopathy (CAR). However, there is limited information on the occurrence, the specificity of autoantibodies in these patients, and their association with clinical symptoms.     

Carcinoma-associated retinopathy: a review with clinical examples

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome. In this survey we report about two further patients with CAR, who were referred to the University Eye Hospital of Tuebingen within a few months. The most common primary tumor associated with CAR is small cell carcinoma of the lung. Case reports about rhabdomyosarcoma, carcinoma of the endometrium, prostate and mamma were also described. The exact pathogenesis of CAR is still unknown. Specific autoantibodies were found against the photoreceptor protein recovering (23-kd retinal CAR antigen). However, this reaction is not present in all patients, and probably other antigens are also involved. Most of the patients experience symptoms of CAR before the primary tumor is detected. Besides glare sensitivity and flashing lights, a rapidly progressive, often asymmetric visual loss may occur. Although paracentral and mid-peripheral scotomas can be found frequently, visual field defects are often quite heterogeneous. Typically, the responses in the electroretinogram (ERG) are markedly reduced, but normal ERGs were also described. The fundus picture in CAR shows sheathing of the retinal vessels, narrowing of the arterioles and clumbing of the retinal pigment epithelium. The prognosis is poor. Frequently there is progression to bilateral loss of vision within a few months. Treatment of the primary tumor does not seem to alter the ocular prognosis. Systemic corticosteroids may be helpful in some patients. Nevertheless, no proven therapeutic regimen is currently available.     

Ocular manifestations of cancer

Cancer may affect the eye and orbit as a direct result of metastatic neoplastic infiltration, compression, or circulating antibodies involving paraneoplastic retinal degeneration. A metastatic tumor to the uvea is the most common form of an intraocular metastatic process. The choroid is the most common site for uveal metastasis; metastases to the ciliary body, iris, retina, optic disk, and vitreous are rare. Approximately one-third of patients have no history of primary cancer at the time of ocular diagnosis. Breast and lung carcinomas for women and lung and gastrointestinal carcinomas for men most commonly metastasize to the eye and orbit. The short-term prognosis for vision is usually good after an individualized therapeutic approach (chemotherapy, hormonal therapy, external beam radiotherapy, or plaque radiotherapy), but the systemic prognosis is poor. The visual paraneoplastic syndromes encompass several distinct clinical and pathological entities including carcinoma-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), and bilateral diffuse melanocytic uveal proliferation (BDUMP). The CAR syndrome affects photoreceptors, MAR is thought to affect bipolar cell function, and BDUMP targets the uveal tract. Identification of circulating antibodies against retinal proteins (recovering, 23-kDa retinal protein; 46-kDa and 60-kDa retinal proteins) serves to recognize the paraneoplastic nature of the patient's symptoms, which frequently develop before the cancer is diagnosed. Anecdotal therapeutic responses are described after systemic steroids, immunoglobulin injection, and plasmapheresis. Recognition of their visual symptoms and ocular findings should alert the ophthalmologist to the possibility of cancer and systemic evaluation should be pursued.     

Paraneoplastic retinopathy

Paraneoplastic retinopathy (PR) mainly includes cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR). Emerging evidences indicate that PR is mediated by immune cross-reaction between circulating antibodies originally generated against remote tumor with antigens expressed on retinal neurons. It is believed that CAR is a consequence of the autoantibodies against the photoreceptors and MAR is the autoantibodies against the retinal ON-bipolar cells. Recoverin autoantibody in serum is closely related to the pathogenesis of CAR, and the inactivation of TRPM1 channel plays a key role in dysfunction of ON-bipolar cells in MAR. PR is characterized by visual dysfunctions, including decreased vision, night blindness, shimmering or flickering, and abnormalities of symbolic electroretinogram appearances. Based on the history of tumors, ophthalmic symptoms, and existance of circulating antibodies, it is easy to make a diagnosis of PR. Immunosuppressants and glucocorticoids may improve the visual dysfuctions in PR subjects.     

Choroidal neovascularization associated with cancer‐associated retinopathy

Purpose: To report an unusual association between cancer‐associated retinopathy (CAR) associated with invasive thymoma and choriodal neovascularization (CNV), treated by photodynamic theraphy (PDT). Methods: A 39‐year‐old man affected with thymoma and paraneoplastic syndrome (myasthenia gravis and diarrhoea) was observed between October 1997 and September 2007. The patient developed progressive visual dysfunction including bilateral visual acuity loss and concentric constriction of visual fields. Ophthalmological, immunological and systemic examinations were performed. Immunological evaluations included an assessment of antibody activity by indirect immunohistochemistry on sectioned rhesus monkey eye, and Western blot reactions upon an extract of pig retina. Results: Fundus ophthalmoscopy and fluorescein angiography revealed retinal vessel attenuation and retinal pigment epithelium degeneration. Electroretinogram suggested both rod and cone dysfunction. Indirect immunohistochemistry identified antibody activity within the photoreceptor outer segments. Western blots on the retina revealed that most of the patient’s antibody activity was focused upon a retinal protein antigen approximating 145 kD. These findings share the commonalities of size and retinal distribution of the interphotoreceptor retinoid‐binding protein (IRBP), a recognized autoantigen. The surgically resected mediastinal tumour was diagnosed as invasive thymoma. No other malignancy has since been found throughout nearly 10 years of follow‐up. In March 2006, the patient developed a subfoveal CNV in his left eye, which was treated by PDT. Conclusion: We describe the third case of paraneoplastic retinopathy associated with invasive thymoma. This is the first example of CAR involving autoantibodies reactive with a retinal protein having the characteristics of the IRBP, and is also the first complicated by CNV treated by PDT.     

Experimental,cancer-induced retinopathy

Autoantibody reactions with various ocular components have been described in different types of paraneoplastic vision loss, and are considered indicators of an activated, and potentially harmful immunologic process. To date, only one subgroup, the 23 kd CAR syndrome, has been linked with hypersensitivity to a single defined retinal protein, recoverin. Inquiries into the cause of this unusual immunologic reaction led to the discovery that this photoreceptor component is expressed by some, but not all small cell carcinomas, the neoplasm most often linked with paraneoplasias. Neoplasia expressing retinal antigens, outside normal distribution, may provoke an immune response resulting in a cancer-induced autoimmune retinopathy, a cause and effect relationship addressing the etiology and pathogenesis of the CAR syndrome. Since only a subset of paraneoplastic retinopathy patients produce autoantibodies reactive with the 23 kd CAR autoantigen, a search was initiated in other subgroups, seeking additional examples of this immunologic cancer connection.

Cultures of small cell lung carcinomas were obtained from the American Type Culture Collection, Human Tumor Bank (ATCC, HTB), each expressing the unique characteristics of the donor. The ability of single cultures to incite the production of anti-retinal antibodies in laboratory animals was investigated through intraperitoneal propagation in ‘Pristane’ induced ascites, followed by an evaluation of the resultant immunologic response.

A culture of small cell carcinoma of the lung, the HTB 175, was found actively expressing a novel retinal protein corresponding in Western blot analyses to that involved in the autoantibody reactions of an immunologically distinct subgroup of paraneoplastic retinopathy patients.     

Síndrome paraneoplásico ocular: retinopatía asociada al cáncer

Case ReportWe review a patient with ocular manifestations of a paraneoplastic syndrome. It was a cancer-associated retinopathy (CAR) in a woman with visual loss, and attenuated and sheathed retinal arterioles. The electroretinography (ERG) showed severe abnormalities of the a and b-waves. The tumour process was not discovered until 6 months later, when a squamous neoplasia that invaded the uterus and vagina was observed.DiscussionParaneoplastic syndromes are a group of manifestations produced as a remote effect of cancer cells. CAR syndrome is caused by autoimmune reactions to retinal antigens induced by aberrant expression of recoverin in cancer tissues. Ophthalmologists must be aware of ocular paraneoplastic signs as they can be the first manifestations of a malignant tumour.     

Ocular manifestations of cancer.

Cancer may affect the eye and orbit by a direct effect of metastatic neoplastic infiltration or compression or by circulating antibodies involving paraneoplastic retinal degeneration. Metastatic tumor to the uvea is the most common form of an intraocular malignant process. The choroid is the most common site for uveal metastasis; metastases to the ciliary body, iris, retina, optic disc, and vitreous are rare. Approximately one third of patients have no history of primary cancer at the time of ocular diagnosis. Breast and lung carcinomas for women and lung and gastrointestinal carcinomas for men most commonly metastasize to the eye and orbit. The short-term prognosis for vision is usually good but the systemic prognosis is poor. The visual paraneoplastic syndromes encompass several distinct clinical and pathologic entities including carcinoma-associated retinopathy, melanoma-associated retinopathy, and bilateral diffuse melanocytic uveal proliferation. The first affects photoreceptors, the second is thought to affect bipolar cell function, and the third targets the uveal tract. Identification of circulating antibodies against retinal proteins (recoverin, 23-kD retinal protein; 46-kD and 60-kD retinal proteins) serves to recognize the paraneoplastic nature of the patient's symptoms, which frequently develop before the cancer is diagnosed. No therapy exists to stop the inexorable progressive loss of vision. Metastasis to the eye and orbit and paraneoplastic disorders represent a very bad prognostic sign. Recognition of their visual symptoms and ocular findings should alert the ophthalmologist to the possibility of cancer and systemic evaluation should be pursued.     

Neuro-ophthalmological paraneoplastic syndromes: a review

Lesions involving the visual system due to the remote effect of cancer are uncommon. Their clinical manifestations are protean. The main symptoms are visual loss, caused by retinopathy or optic neuritis, and abnormal eye movements. Cancer-related retinopathy (CAR) has been primarily described in patients with small-cell lung carcinoma, and it is distinct from melanoma associated retinopathy (MAR), and the retinopathy caused by bilateral diffuse uveal melanocytic proliferation (BDUMP) observed in patients with various neoplasias. The main underlying tumours in patients with paraneoplastic optic neuritis are lung and breast carcinomas. Eye movement disorders consist of opsoclonus, associated with neuroblastoma in infants and children and various tumours in adults, and ophtalmoplegia caused by paraneoplastic myasthenia gravis or paraneoplastic brainstem encephalitis. The differential diagnosis of the neuro-ophthalmological paraneoplastic syndromes includes primarily metastatic and treatment-related lesions. In some patients the paraneoplastic nature of the ophthalmological disorder my by proven by specific serum antibodies. These antibodies are also markers of the underlying and often non-diagnosed cancer, but their pathogenic role remains unproven.     

CAR syndrome (carcinoma-associated retinopathy syndrome) associated with an adenocarcinoma of the cervix

BACKGROUND: CAR is a rare paraneoplastic syndrome. It is most commonly associated with small-cell carcinoma of the lung. Specific autoantibodies exist not only against the retina but also against other ocular structures. They induce apoptotic death of retinal photoreceptor cells. CASE REPORT: We report about a 68-year-old patient who presented in February 2003 with progressive visual dysfunction including visual acuity loss and visual field defects of unknown origin, which first manifested in the year 1998. RESULTS: We found a visual acuity of 0.1 in both eyes and concentric visual field defects. The scotopic and photopic electroretinogram was markedly reduced. Uveitis intermedia in both eyes, narrowing of the vessels, especially of the arterioles, optic atrophy and window defects in the retinal pigment epithelium were observed on fluorescein angiography. Due to the patient's report about a resection of an adenocarcinoma of the cervix in June 2002, she was diagnosed as having CAR syndrome. Serologic screening by Western blot analysis revealed different specific autoantibodies against retinal proteins. The patient was treated with corticosteroid pulse therapy. The follow-up showed stable findings. CONCLUSIONS: In patients with progressive visual loss, concentric visual field defects and pathological electroretinogram as well as evidence of uveitis, a CAR syndrome has to be ruled out. One has to take into consideration that visual dysfunction can appear before the primary cancer is diagnosed.     

Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies

PURPOSE: Paraneoplastic and autoimmune retinopathies are immunologically mediated retinal degenerations that are associated with antibodies directed against any of several retinal proteins, including alpha-enolase. We report the clinical and electrophysiological features of antienolase retinopathy in contrast to the features of antirecoverin retinopathy. DESIGN: Retrospective, observational case series. METHODS: Patients were referred for evaluation of unexplained acquired visual symptoms, including photopsias, and loss of visual acuity or field considered of possible retinal origin. Full-field and multifocal electroretinograms (ERGs) were performed. Sera from patients were examined for antiretinal antibodies by Western blot analysis using proteins extracted from human retinas and by immunohistochemistry; antienolase was confirmed by incubating patient sera with purified alpha-enolase. RESULTS: Of 87 patients with unexplained retinal visual symptoms associated with abnormal ERGs, 37 (43%) demonstrated autoantibodies to retinal antigens, including 12 against alpha-enolase, of whom 4 had cancer. Initial visual loss was typically central and often asymmetric. The ERGs demonstrated mostly normal rod responses but central cone abnormalities (evident on multifocal ERG) and, for many, global cone abnormalities. Seven patients developed optic disk pallor. Corticosteroid and immunosuppressive therapy, when attempted, was clinically ineffective. CONCLUSIONS: Antienolase retinopathy is a protean autoimmune retinopathy that characteristically presents with cone dysfunction. The visual impairment and course vary from relative stability for years to slow progression with loss of central vision. With time, optic disk pallor can evolve, presumably from attrition of ganglion cells.     

Paraneoplastic Vitelliform Retinopathy: Clinicopathologic Correlation and Review of the Literature

Traditionally, the paraneoplastic retinopathies have been classified into two groups: melanoma-associated retinopathy (MAR) and cancer-associated retinopathy. MAR occurs in individuals with metastatic cutaneous or uveal melanoma and is characterized by nyctalopia, photopsias, and variable vision loss. In most cases, the fundus is essentially normal in appearance. More recently, there have been multiple reports of a MAR-like retinopathy with associated detachments of the retinal pigment epithelium and neurosensory retina. Such a clinical presentation has been termed paraneoplastic vitelliform retinopathy. We describe an 80-year-old man with metastatic cutaneous melanoma who developed paraneoplastic vitelliform retinopathy. For the first time, histopathology from enucleation specimens provides a clinicopathologic disease correlation with focal abnormalities in the inner nuclear and outer plexiform layers.     

Acute progressive paravascular placoid neuroretinopathy with negative-type electroretinography in paraneoplastic retinopathy

Purpose

Paraneoplastic retinopathy can be the first manifestation of systemic malignancy. A subset of paraneoplastic retinopathy is characterized by negative-type electroretinography (ERG) without fundus abnormality. Here we describe the multimodal imaging and clinico-pathological correlation of a unique case of acute progressive paravascular placoid neuroretinopathy with suspected retinal depolarizing bipolar cell dysfunction preceding the diagnosis of metastatic small cell carcinoma of the prostate.

Methods

ERG was performed according to the International Society for Clinical Electrophysiology of Vision standards. Imaging modalities included near-infrared reflectance, blue-light autofluorescence, fluorescein and indocyanine green angiographies, spectral domain optical coherence tomography, ultra-widefield colour and green-light autofluorescence imaging, microperimetry and adaptive optics imaging. Patient serum was screened for anti-retinal antibodies using western blotting. Immunostaining and histological analyses were performed on sections from human retinal tissues and a patient prostate biopsy.

Results

Serial multimodal retinal imaging, microperimetry and adaptive optics photography demonstrated a paravascular distribution of placoid lesions characterized by hyper-reflectivity within the outer nuclear layer resembling type 2 acute macular neuroretinopathy. There was no visible lesion within the inner nuclear layer despite electronegative-type ERG. Six months later, the patient presented with metastatic small cell carcinoma of the prostate. Tumour cells were immunopositive for glyceraldehyde-3-phosphate dehydrogenase, enolase and recoverin as well as neuroendocrine markers. The patient’s serum reacted to cytoplasmic and nuclear antigens in the prostate biopsy and in human retina. Anti-retinal antibodies against several antigens were detected by both commercial and in-house western blots.

Conclusions

A spectrum of autoreactive anti-retinal antibodies is associated with a unique phenotype of acute progressive paravascular placoid neuroretinopathy resulting in degeneration of photoreceptor cells, inner retinal dysfunction and classic electronegative ERG in paraneoplastic retinopathy. Detailed clinical, functional and immunological phenotyping of paraneoplastic retinopathy illustrated the complex mechanism of paraneoplastic syndrome.

     

Cancer-associated retinopathy associated with invasive thymoma

PURPOSE: To report a case of cancer-associated retinopathy associated with invasive thymoma. DESIGN: Interventional case report. METHOD: A 41-year-old Japanese woman was observed between February 1998 and May 2001. Ophthalmologic examinations and systemic examinations were performed. The patient received treatment including corticosteroid pulse therapy, plasmapheresis, and thymectomy. RESULTS: The patient developed progressive visual dysfunction including bilateral visual acuity loss, concentric contraction of visual fields, and color vision loss. In both eyes, retinal vessel attenuation and retinal pigment epithelium degeneration were observed with fundus ophthalmoscopy and fluorescein angiography. Response in electroretinogram was reduced, suggesting both rod and cone dysfunction. Autoantibody against 23-kD cancer-associated retinopathy (CAR) antigen (antirecoverin antibody) was detected in the patient's serum. A mediastinal tumor that was histopathologically diagnosed as invasive thymoma was detected and was surgically resected. During more than 3 years of follow-up, no other malignancy was detected despite extensive systemic evaluation. The patient also suffered from subclinical myasthenia gravis. Although temporary improvement of visual function was observed after treatment with steroid pulse therapy and plasmapheresis' light perception of each eye was lost in the end. CONCLUSIONS: The patient was diagnosed as having CAR. Invasive thymoma was considered to be the causative tumor because there had been no evidence that suggested other systemic malignancy during more than 3 years of follow-up.     

Paraneoplastic vitelliform retinopathy associated with cutaneous or uveal melanoma and metastases

PURPOSE: To report unusual vitelliform fundus findings in three cases of paraneoplastic retinopathy associated with metastasised cutaneous or uveal melanoma and in one case, a unique immunoreactivity response. PATIENTS AND METHODS: Observational case series. The histories of three patients with MAR-like paraneoplastic retinopathy were reviewed. Electroretinography, Goldmann perimetry, fluorescein angiography, and in one case optical coherence tomography, immunohistochemistry and Western blotting were performed. RESULTS: All patients revealed similar paraneoplastic vitelliform retinal abnormalities. Symptoms in two cases differed from the classical MAR syndrome. In one case, western blotting and immunohistochemistry demonstrated antibodies against 120-kDa, a soluble photoreceptor protein. No immunoreactivity to retinal bipolar cells was detected. CONCLUSION: The clinical, electrophysiological, and immunological findings in our patients suggest a melanoma associated paraneoplastic origin, like in MAR syndrome. However contrary to MAR syndrome, this paraneoplastic vitelliform retinopathy exhibits a peculiar fundus picture, consisting of serous macular detachment and nummular vitelliform lesions in the posterior pole. This could be an unusual presentation of MAR or a separate paraneoplastic entity.     

Cutaneous melanoma-associated paraneoplastic retinopathy: histopathologic observations.

PURPOSE: To describe the retinal histopathology of paraneoplastic retinopathy associated with cutaneous melanoma. METHODS: A 59-year-old man had visual loss attributable to paraneoplastic retinopathy and died of metastatic cutaneous melanoma. His eyes were studied by conventional histopathologic techniques. RESULTS: Histopathologic examination of both eyes disclosed a marked reduction in the density of bipolar neurons in the inner nuclear layer; photoreceptor cell neurons in the outer nuclear layer were normal. Ganglion cells were present, although many showed evidence of transsynaptic atrophy. CONCLUSION: The histopathologic changes observed are consistent with clinical, immunologic, and electrophysiologic data that implicate the bipolar cell as the major site of the paraneoplastic process in cutaneous melanoma-associated retinopathy.     

Paraneoplastic syndromes associated with visual loss

PURPOSE OF REVIEW: The recent literature was reviewed to analyze the developments in the diagnosis, pathogenesis, and immunology of this group of paraneoplastic syndromes. Clinical features and pathologic findings are summarized. RECENT FINDINGS: The mechanism of cell death in cancer-associated retinopathy appears to occur through apoptotic pathways. Caspase inhibitors and a calcium antagonist have been used in animal models to block or suppress the effect of the antirecoverin antibodies on the retina with significant response. These agents are possible treatment options for cancer-associated retinopathy. Aberrant expression of recoverin by tumor cells does not necessarily induce antirecoverin antibodies and cancer-associated retinopathy. Many tumors, not just those producing the clinical picture of cancer-associated retinopathy, have been shown to express recoverin. Recoverin appears to play a functional role in tumor cells, and antirecoverin antibodies may have tumor-suppressing effects. Further research into this area may help design epitope-based immunotherapy for patients with recoverin-expressing tumors. Further evidence has emerged to support the initial observation that depolarizing bipolar cells are the likely retinal target in melanoma-associated retinopathy. Intravitreal injection of melanoma-associated retinopathy serum produced electroretinogram changes in animals very similar to the clinical findings in humans. Many new antibodies and antigens had been discovered to be linked to various paraneoplastic syndromes. Anti-collapsing response-mediating protein-5 is likely to be an important one; it was found to be the second most common autoantibody related to paraneoplastic neurologic syndromes. SUMMARY: Further research into the functional role of recoverin in cancer cells may advance our understanding in cancer immunology. Immunotherapy may be possible if a specific epitope of recoverin can be found to contain the antigenic site for antitumor antibodies and not cross-react with retinal antigens. Research into the pathogenesis of the other paraneoplastic syndromes is required for a better understanding and treatment of these rare conditions. The missing link between primary cutaneous melanoma and uveal melanocytes still eludes investigators in bilateral diffuse uveal melanocytic proliferation. The discovery of the missing link may provide us with some understanding of the development of uveal melanoma.     

Electrophysiological findings in paraneoplastic retinopathy

Paraneoplastic retinopathy is a cancer-related non-metastatic retinopathy mainly associated with lung cancer. We examined two patients with presumed paraneoplastic retinopathy, both ophthalmologically and electrophysiologically. Both patients presented with initial visual complaints of moderate reduction of visual acuity. No specific fundus anomaly was found in the fundus except for a mild attenuation of the retinal arteries. The electroretinogram and pattern reversal visual evoked responses were either markedly reduced in amplitude or non-recordable. The electrooculogram recorded in one patient demonstrated a markedly reduced light peak/dark trough ratio. These results indicate the presence of a severe and diffuse bilateral retinal dysfunction, despite the relatively good visual acuities and mild fundus changes. Electrophysiological evaluations play an important role in the diagnosis of paraneoplastic retinopathy.     

Retinal anti-bipolar cell antibodies in a patient with paraneoplastic retinopathy and colon carcinoma

PURPOSE: To describe clinical, electrophysiologic, and immunologic features of a unique paraneoplastic retinopathy with characteristics of cancer-associated and melanoma-associated retinopathy. METHODS: Serial assessment of clinical visual function, electroretinography, and assays of anti-retinal antibodies. RESULTS: A 51-year-old woman with progressive visual glare for 1 year had normal visual acuity and color vision, paracentral scotomas, and a normal-appearing retina. Electroretinography revealed no responses of the right eye and attenuated responses of the left eye, especially those recorded under scotopic conditions. Anti-bipolar antibodies were detected. Subsequent evaluation uncovered adenocarcinoma of the colon. Several months after resection of the tumor and chemotherapy, no evidence existed of cancer or anti-bipolar cell antibodies, and electroretinography responses were markedly improved. CONCLUSION: The presence of anti-bipolar cell antibodies in a patient with retinal dysfunction is not specific of melanoma-associated retinopathy. Effective treatment of cancer may result in elimination of associated anti-retinal antibodies and improved retinal function.