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.     

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.     

副肿瘤性视网膜病变的发病机制及临床特点

副肿瘤性视网膜病变(PR)是一种少见的副肿瘤综合征,因肿瘤表达异常抗原,产生自身抗体与视网膜自身抗原发生交叉免疫反应,导致病变.PR包括癌症相关性视网膜病变(CAR)、黑色素瘤相关性视网膜病变(MAR)及双侧弥漫性葡萄膜黑色素细胞增生症(BDUMP).目前发现多种导致CAR的自身抗体,如抗恢复蛋白(recoverin)抗体、抗α烯醇化酶抗体及抗转导蛋白-α(transducin-α)抗体等,可以与视网膜相应的自身抗原结合;导致MAR的自身抗体最主要为抗TRPM1抗体,可以与视网膜双极细胞离子通道的TRPM1结合;导致BDUMP的抗体目前只发现抗recoverin抗体和抗热休克蛋白70(HSP70)抗体.PR的临床表现主要为短期内双眼视力下降及夜盲等,眼底表现可正常或轻度异常,视网膜电图(electroretinogram,ERG)表现为不同类型的异常,其中BDUMP有双眼多发橘红色斑块等特殊表现.临床表现往往因自身抗体类型的不同而存在差异,主要原因在于针对自身抗原的不同生理作用,表现为发病时间、进展速度、严重程度及ERG表现等.目前对于PR的治疗主要为治疗原发肿瘤,及针对自身抗体进行糖皮质激素、血浆置换及免疫球蛋白等单独及联合的治疗.     

Presumed CMV associated necrotizing retinopathy in a non-HIV immunocompromised host

Herpetic necrotizing retinitis is caused by the herpesvirus group of viruses, including cytomegalovirus (CMV). Reports defining causative viruses have shown CMV to be a rare cause of acute retinal necrosis. In fact, there is only one report in the literature of CMV associated with progressive outer retinal necrosis, which is most commonly associated with Varicella zoster virus. A case is presented of CMV-related necrotizing retinopathy concurrent with subtle signs of herpetic retinitis in an immunocompromised patient, highlighting the spectrum of response of herpetic retinopathies.     

Severe course of cutaneous melanoma associated paraneoplastic retinopathy.

BACKGROUND--Melanoma associated retinopathy (MAR) is a paraneoplastic syndrome in metastatic cutaneous melanoma presenting with nightblindness, light sensations, mild visual loss, and reduced b-waves in the electroretinogram (ERG). METHODS--A patient with MAR was followed for a period of 25 months with repeated examinations including visual field testing and recording of standard electro-oculography, standard ERG, and photopic On and Off responses. RESULTS--A male patient with a very severe course of MAR is described. In addition to the clinical signs seen in previous patients, severe visual deterioration and vitreous inflammation were the predominant signs. The vitreous inflammation resolved after systemic corticosteroid therapy. Nightblindness and the reduced b-waves in the ERG remained unchanged during the follow up period. However, further visual deterioration and paracentral scotomas developed. Dark adaptation was markedly abnormal. Photopic On responses were reduced, but Off responses were preserved. Antibodies against retinal bipolar cells were isolated from blood samples of this patient. CONCLUSION--Vitreous inflammation may mask the diagnosis of MAR. ERG findings indicate that the more severe and progressive course is the result of local retinal changes and not progressive generalised retinal degeneration.     

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.     

Selective immunohistochemical staining in the paraneoplastic retinopathy syndrome.

BACKGROUND: The mechanism leading to visual loss in paraneoplastic retinopathy is not known. An autoimmune process has been imputed based on immunologic investigations of several patients and by analogy to certain other paraneoplastic syndromes. METHODS: Two patients with documented small cell carcinoma of the lung who had clinical evidence of paraneoplastic retinopathy are described. Histopathologic examination of the retina from one patient and immunohistochemical staining of human retina with serum from control subjects and both patients were performed. RESULTS: Electroretinograms demonstrated dysfunction of photoreceptors in both patients, with predominant loss of rod function in one patient. Post mortem examination showed patchy loss of photoreceptors of the extramacular retina and relative sparing of cones, findings consistent with the clinical and electrophysiologic test results. Serum from both patients stained the retina in an identical manner, with restriction of the stain to the outer retina. Stain was present over the outer plexiform layer, the outer nuclear layer, and the inner and outer segments of most photoreceptors. A sharp demarcation was present between those areas that did and did not stain. All rod inner and outer segments appeared to stain, and many cone inner segments were not stained. Immunologic tests obtained elsewhere did not show serum antibody to the 23 kD protein. CONCLUSION: These findings support the concept of an autoimmune pathogenesis by showing selectivity of the immune response and correlation between the apparent target of the immune response and the clinical and pathologic findings. The mechanism by which cell loss occurs in the retina is not answered by this study. The absence of antibody to the 23 kD protein does not exclude the diagnosis of paraneoplastic retinopathy.     

Presumed exudative retinal detachment after cryotherapy in retinopathy of prematurity.

Cryotherapy of the peripheral avascular retina in selected cases of retinopathy of prematurity has been shown to reduce the incidence of posterior retinal detachment, retinal fold involving the macula, and retrolental tissue. Although exudative retinal detachments have been described after cryotherapy during scleral buckling procedures, to our knowledge, this observation has not been reported after cryotherapy in retinopathy of prematurity. We describe such a case.     

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.     

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.

     

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.     

Presumed histoplasmosis

In a follow-up study of 30 eyes of 25 patients, three types of lesions could be distinguished: 1) the classical pigment ring, found in 13 eyes of 12 patients; 2) the cystous type, observed in 4 eyes of 4 patients, and 3) the multilocular type, found in 13 eyes of 9 patients. Up to the present, the cystous type of histoplasmosis has not been described.     

Presumed nasolacrimal endometriosis

A 13-year-old girl was admitted with a complaint of cyclic bleeding from the left inferior punctum with menstruation. Crusted hemorrhage was noticed in the tear meniscus of the left eye and just inferior to the left caruncle. With gradient-echo magnetic resonance imaging, the hemorrhagic tissue in the nasolacrimal canal was demonstrated and the diagnosis of nasolacrimal endometriosis was made. Nasolacrimal endometriosis is a rare ocular condition. Its management and histologic diagnosis remain challenging.