Research progress of autoimmune retinopathy / 中华实验眼科杂志

Autoimmune retinopathy (AIR) is a rare immune retinopathy characterized by decreased visual acuity, scotoma, visual field defect, and photoreceptor dysfunction.AIR is divided into paraneoplastic AIR (pAIR) and non-neoplastic AIR (npAIR). pAIR is further divided into cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), and bilateral diffuse uveal melanocytic proliferation (BDUMP). Circulating anti-retinal antibodies often exist in peripheral blood of patients with various types of AIR, accompanied by electroretinogram abnormalities, but no significant abnormality in fundus examination (except BDUMP). A variety of anti-retinal antibodies such as anti-recoverin protein antibody and anti-α-enolase antibody have been identified in the serum of AIR patients.However, anti-retinal antibodies can also be negative in some AIR patients' serum.At present, the diagnostic criteria and laboratory examination criteria for AIR are not uniform, and there are large differences in clinical examination performance among patients, which may lead to misdiagnosis and missed diagnosis.Therefore, a thorough examination is required to rule out other possible causes before making a speculative diagnosis.So far, the treatments for different types of AIR are not unified.Most clinicians choose a combination of various immunomodulatory therapies, including systemic or topical application of corticosteroids, intravenous immunoglobulin, plasmapheresis, and the use of antimetabolites or anti-CD20 monoclonal antibody.The clinical characteristics of different AIR types, serum anti-retinal autoantibodies detection, differential diagnosis and treatment prognosis of AIR were reviewed in this article to improve the understanding of clinicians and researchers toward the disease, and to achieve early diagnosis and early treatment of AIR.

Clinical features of cancer-associated retinopathy / 中华实验眼科杂志

Objective To analyze the clinical features of cancer-associated retinopathy (CAR).Methods The clinical data of 10 patients who diagnosed as CAR during 5 years were retrospectively analyzed.All patients underwent detailed ocular examinations,including electroretinogram (ERG),optical coherence tomography (OCT),visual field (VF) and autofluorescence(AF).Results The primary malignancy was lung carcinoma in 3 patients,thymoma in 3 patients,thyroid carcinoma in 1 patients,maxillary sinus tumor in 1 patients,nasopharyngeal carcinoma in 1 patients and rectal cancer in 1 patients.All patients complained progressive visual reducing.Three patients manifested night blindness.The best corrected visual acuity (BCVA)＜0.1 was in three eyes,≤0.1-＜0.5 in seven eyes,and ≥0.5 in ten eyes.Patients showed normal fundi or mild abnormality.OCT images showed disorganization and/or loss of the ellipsoid zone in the macular area in 4 patients,and other six patients had only central foveal ellipsoid zone preserved.Eight patients had moderately or severely reduced ffERG,and 2 patients demonstrated electro-negative ERG.Five patients revealed peripheral visual defect.AF images were from normal to low or high AF patches in the posterior pole and mid-peripheral retina.Conclusions The clinical manifestations of CAR are varied as common characteristics of progressive visual decrease with or without night blindness,visual field defect and abnormal ffERG recording.

Paraneoplastic retinopathy associated with occult bladder cancer.

The aim was to report the first case of cancer‑associated retinopathy (CAR) presenting before bladder cancer diagnosis. A 71‑year‑old woman with a history of bilateral vision loss underwent subsequent complete ophthalmic examination include a fluorescein angiography, full‑field electroretinogram (ERG), serology including serum antibodies for CAR, and positron emission tomography‑computed tomography (PET‑CT) scan. The patient was diagnosed with Cite this article as: Nivean M, Muttuvelu DV, Afzelius P, Berman DC. Paraneoplastic retinopathy associated with occult bladder cancer. Indian J Ophthalmol 2016;64:248-50. This is an open access article distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical terms. For reprints contact: reprints@medknow.com bladder carcinoma revealed by PET‑CT. Timely recognition of this entity may be crucial for an increased patient survival thus adult onset progressive photoreceptor dysfunction, confirmed by ERG, should alert to a possible remote effect of known or occult malignancy. In the latter, PET‑CT may be exploited as a powerful diagnostic tool.

Intravenously Administered Anti-recoverin Antibody Alone Does Not Pass through the Blood-Retinal Barrier

PURPOSE: Cancer-associated retinopathy is a paraneoplastic retinal degeneration which may primarily result from auto-immune mediated apoptosis. It has been hypothesized that high titer of auto-antibodies are able to cross the blood-retinal barrier (BRB) and to enter retinal cells to activate apoptotic pathway which has been already well-established. However, it still remains to be elucidated whether auto-antibodies could cross BRB in the retina. Herein, we demonstrated that intravenously administrated anti-recoverin antibodies could not pass through BRB and not lead to retinal cell death. METHODS: Anti-recoverin antibody was intravenously injected to C57BL/6 mice, which were sacrificed 1 and 7 days to obtain eye. Vascular endothelial growth factor was intravitreally injected to induce BRB breakdown, which was confirmed by fluorescein angiography and western blotting for zonula occludens (ZO)-1, ZO-2 and occludin. To investigate the location of anti-recoverin antibody in the retina, immunofluorescein was performed. The retinal toxicity of intravenous anti-recoverin antibody was evaluated by histological examination and transferase-mediated dUTP nick-end labeling. Immunofluorescein staining for glial fibrillary acidic protein was done to address glial activation as well. RESULTS: Intravenously administrated anti-recoverin antibodies were exclusively distributed on retinal vessels which were co-localized with CD31, and led to neither increase of glial fibrillary acidic protein expression, as an indicator of retinal stress, nor apoptotic retinal cell death. Moreover, even in the condition of vascular endothelial growth factor-induced BRB breakdown, anti-recoverin antibodies could not migrate across BRB and still remained on retinal vessels without retinal cytotoxicity. CONCLUSIONS: Our results suggest that high titer of intravascular anti-recoverin antibodies could not penetrate into the retina by themselves, and BRB breakdown mediated by dysregulation of tight junction might not be sufficient to allow anti-recoverin antibodies to pass through BRB.

Cancer-associated Nummular Loss of the Retinal Pigment Epithelium

PURPOSE: To report a case of cancer-associated nummular loss of the retinal pigment epithelium. METHODS: A 47-year-old man with a history of hepatocellular carcinoma presented with three weeks of bilateral visual loss. His best-corrected visual acuity was 20/40 in each eye. He had multiple round confluent grayish-brown patches at the level of retinal pigment epithelium, and no pigmented choroidal lesions. Fluorescein angiography showed circular areas of transmission defect and indocyanine green angiography showed early hyperfluorescence, corresponding with the multiple round confluent patches. CONCLUSIONS: We report a case of visual paraneoplastic syndrome which showed nummular loss of the pigment epithelial cells which distinguishes the clinical component of BDUMP syndrome.

A Case of Cancer-Associated Retinopathy with Small Cell Lung Cancer

PURPOSE: To report a case of cancer-associated retinopathy developed in a patient with small cell lung cancer, which is a kind of paraneoplastic syndrome. METHODS: A 78-year-old woman presented complaining of decreased visual acuity and visual field that had developed about 15 days previously. She was diagnosed with small cell lung cancer 1.5 years ago and underwent 3 cycles of chemotherapy. At presentation, the best-corrected visual acuity was hand motion in both eyes and there was no afferent pupillary defect. Slit-lamp biomicroscopic examination revealed no specific abnormality in the anterior segment of either eye, and intraocular pressure was normal. Posterior segment examination demonstrated remarkable arteriolar narrowing in both eyes, but there was little doubt about the presence of an optic nerve lesion such as optic disc edema or pallor. RESULTS: Fluorescein angiography and brain magnetic resonance imaging (MRI) revealed no significant abnormalities. However, electroretinograms (ERG) demonstrated marked reduction in the a and b waves. Visual evoked response was delayed for the latency period. She was treated with systemic steroid, after which her visual acuity gradually improved.

A Case of Cancer Associated Retinopathy with Small Cell Lung Carcinoma / 결핵및호흡기질환

Cancer associated retinopathy (CAR) syndrome is a very rare ocular manifestation of paraneoplastic syndrome, and is characterized clinically by progressive visual impairment. Immune cross-reactivity between antigens in the cancerous tissue and antigens in the retina may play an important role in its pathogenesis, and most of cases are associated with lung carcinoma, particularly small cell lung cancer. The clinical triad of CAR is described as photosensitivity, ring scotomata, and an attenuated retinal arterial caliber. Here, we report a 61-year old male patient with CAR syndrome, who had small cell lung carcinoma in the stage of limited disease, with a brief review of the relevant literature.