Autoimmune Retinopathy Research Articles

Autoimmune Retinopathy, Testing, and Its Controversies.

The purpose of this revision is to sumarize the most important clinical features of the autoimune retinopathies (AIRs). AIRs are a group of inflammatory conditions affecting the retina characterized by progressive unexplained visual loss, abnormalities and contraction in visual fields, photoreceptor and electroretinographic dysfunction, and the presence of circulating anti-retinal antibodies. The pathogenesis of AIR remains unclear and various antiretinal antibodies have been associated to the disease. The diagnosis of AIR is based on a particular clinical presentation along with the detection of serum antiretinal antibodies. Numerous anti-inflammatory therapeutic alternatives have been described for the treatment of AIR, nevertheless there is no consensus on treatment protocol. Because of its association with different types of malignant tumors, the early diagnosis, multi-disciplinary approach and prompt treatment should be warranted.

Atypical non-paraneoplastic autoimmune retinopathy with anti-recoverin antibodies: a case report

Autoimmune retinopathy (AIR) is caused by antiretinal antibodies damaging the retinal tissue, classified as paraneoplastic or non-paraneoplastic. Non-paraneoplastic AIR usually presents as a rapidly progressive and often asymmetrical visual loss with an unfavorable visual prognosis. Only a few cases of non-paraneoplastic AIR associated with anti-recoverin antibodies have been described in literature.

Autoimmune retinopathy: clinical, electrophysiological, and immunological features in nine patients with long-term follow-up.

We aim to report on the clinical, imaging, immunological, and electrophysiological features of patients with autoimmune retinopathy (AIR) with long-term follow-up. Single-center, retrospective study of a consecutive group of AIR patients treated in a tertiary academic medical center. Included were nine patients with a mean ± SD age at presentation of 65 ± 13years and a median follow-up of 63months (range 18-120). Five patients were known to have cancer. Median interval between onset of ocular symptoms and diagnosis of AIR was 36months. Mean baseline and final LogMAR visual acuity were 0.72 ± 0.9 and 1.1 ± 1.2, respectively (p = 0.17). The most common funduscopic findings included optic atrophy and bone-spicule-like pigmentation. Thinning of the nerve fiber layer was the most frequent optical coherence tomographic abnormality. Electroretinographic (ERG) recordings demonstrated variably reduced cone- and rod-derived amplitudes in the majority of eyes at presentation. The most commonly detected anti-retinal antibody was anti-α-enolase. Treatment included immunomodulatory therapy and plasmapheresis. ERG tests showed stability in 64% of eyes throughout the treatment period. This study highlights the importance of maintaining a high index of suspicion of AIR, particularly in late middle-aged and elderly patients with "unexplained" visual loss, in light of the non-specific posterior segment signs and the inconsistency of the routinely used ancillary tests.

Anti–Interleukin-6 Antibodies for Autoimmune Retinopathy with Macular Edema

In this cohort of patients with non-paraneoplastic autoimmune retinopathy and cystoid macular edema (CME), treatment with anti-interleukin-6 antibodies was associated with reduced CME, partial restoration of the ellipsoid zone on optical coherence tomography, and a trend towards improved visual acuity.

Autoantibody profiles and clinical association in Thai patients with autoimmune retinopathy

Autoimmune retinopathy (AIR) is a rare immune-mediated inflammation of the retina. The autoantibodies against retinal proteins and glycolytic enzymes were reported to be involved in the pathogenesis. This retrospective cohort study assessed the antiretinal autoantibody profiles and their association with clinical outcomes of AIR patients in Thailand. We included 44 patients, 75% were females, with the overall median age of onset of 48 (17–74, IQR 40–55.5) years. Common clinical presentations were nyctalopia (65.9%), blurred vision (52.3%), constricted visual field (43.2%), and nonrecordable electroretinography (65.9%). Underlying malignancy and autoimmune diseases were found in 2 and 12 female patients, respectively. We found 41 autoantibodies, with anti-α-enolase (65.9%) showing the highest prevalence, followed by anti-CAII (43.2%), anti-aldolase (40.9%), and anti-GAPDH (36.4%). Anti-aldolase was associated with male gender (P = 0.012, OR 7.11, 95% CI 1.54–32.91). Anti-CAII showed significant association with age of onset (P = 0.025, 95% CI − 17.28 to − 1.24), while anti-α-enolase (P = 0.002, OR 4.37, 95% CI 1.83–10.37) and anti-GAPDH (P = 0.001, OR 1.87, 95% CI 1.32–2.64) were significantly associated with nonrecordable electroretinography. Association between the antibody profiles and clinical outcomes may be used to direct and adjust the treatment plans and provide insights in the pathogenesis of AIR.

Comparison of clinical characteristics in patients with acute zonal occult outer retinopathy according to anti-retinal antibody status.

To evaluate the clinical characteristics of patients with acute zonal occult outer retinopathy (AZOOR), according to the presence or absence of anti-retinal antibodies (ARAs) that are frequently detected in autoimmune retinopathy. Retrospective observational case series. This study included 33 patients with acute-stage AZOOR who had been followed up for more than 6months after the initial visit. The median follow-up period was 26months. Immunoblot analyses were used to detect autoantibodies for recoverin, carbonic anhydrase II, and α-enolase in serum from these patients. Main outcome measures comprised clinical factors at the initial and final visits, including best-corrected visual acuity, mean deviation on Humphrey perimetry, and retinal morphology, which were statistically compared between patients with AZOOR who exhibited ARAs and those who did not. At least one serum ARA was detected in 42% of patients with AZOOR. There were no significant differences in clinical factors between the two groups, including follow-up period, best-corrected visual acuity and mean deviation at the initial and final visits, a-wave amplitude on single-flash electroretinography at the initial visit, and frequencies of improvement of the macular ellipsoid zone and AZOOR recurrence. Our findings suggest that the presence of ARAs did not influence visual outcomes or outer retinal morphology in patients with AZOOR.

Changes in choroidal imaging parameters following adalimumab therapy for refractory noninfectious uveitis.

To evaluate the short-term change in choroidal structure following adalimumab (ADA) treatment in refractory noninfectious uveitis. This was a retrospective study of 33 eyes from 18 patients with refractory noninfectious uveitis. Subfoveal choroidal thickness (SFCT), the choroidal stromal index (CSI) defined as the proportion of stromal area to the total choroidal area were used as choroidal imaging parameters and were evaluated by enhanced depth imaging optical coherence tomography (EDI-OCT). The change in these parameters in the 2months following initiation of ADA was analysed. A linear mixed-effect model was used to assess the effect of ADA treatment. The causes of uveitis were Vogt-Koyanagi-Harada disease (VKHD) (42.4%), presumed autoimmune retinopathy (15.2%), others (12.1%) and unclassified (30.3%). In the analysis of all eyes, the SFCT was 309.7 ± 113.1μm at baseline, 295.7 ± 114.5μm at 1month and 275.2 ± 98.8μm at 2months after ADA initiation (P < 0.001). The CSI was 0.275 ± 0.050 at baseline, 0.273 ± 0.068 at 1month and 0.273 ± 0.046 at 2months (P = 0.785). In the subgroup analysis, the SFCT decreased significantly from baseline to 2months in VKHD eyes (P= 0.007) and unclassified eyes (P= 0.034). There was no significant change in CSI in either subgroup. In the assessment of short-term response to ADA treatment in uveitic eyes, using EDI-OCT, the SFCT appears to be more effective as a choroidal imaging biomarker than the CSI, especially in VKHD eyes.

Using bioinformatic protein sequence similarity to investigate if SARS CoV-2 infection could cause an ocular autoimmune inflammatory reactions?

Although severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection have emerged globally, findings related to ocular involvement and reported cases are quite limited. Immune reactions against viral infections are closely related to viral and host proteins sequence similarity. Molecular Mimicry has been described for many different viruses; sequence similarities of viral and human tissue proteins may trigger autoimmune reactions after viral infections due to similarities between viral and human structures. With this study, we aimed to investigate the protein sequence similarity of SARS CoV-2 with retinal proteins and retinal pigment epithelium (RPE) surface proteins. Retinal proteins involved in autoimmune retinopathy and retinal pigment epithelium surface transport proteins were analyzed in order to infer their structural similarity to surface glycoprotein (S), nucleocapsid phosphoprotein (N), membrane glycoprotein (M), envelope protein (E), ORF1ab polyprotein (orf1ab) proteins of SARS CoV-2. Protein similarity comparisons, 3D protein structure prediction, T cell epitopes-MHC binding prediction, B cell epitopes-MHC binding prediction and the evaluation of the antigenicity of peptides assessments were performed. The protein sequence analysis was made using the Pairwise Sequence Alignment and the LALIGN program. 3D protein structure estimates were made using Swiss Model with default settings and analyzed with TM-align web server. T-cell epitope identification was performed using the Immune Epitope Database and Analysis (IEDB) resource Tepitool. B cell epitopes based on sequence characteristics of the antigen was performed using amino acid scales and HMMs with the BepiPred 2.0 web server. The predicted peptides/epitopes in terms of antigenicity were examined using the default settings with the VaxiJen v2.0 server. Analyses showed that, there is a meaningful similarities between 6 retinal pigment epithelium surface transport proteins (MRP-4, MRP-5, RFC1, SNAT7, TAUT and MATE) and the SARS CoV-2 E protein. Immunoreactive epitopic sites of these proteins which are similar to protein E epitope can create an immune stimulation on T cytotoxic and T helper cells and 6 of these 9 epitopic sites are also vaxiJen. These result imply that autoimmune cross-reaction is likely between the studied RPE proteins and SARS CoV-2 E protein. The structure of SARS CoV-2, its proteins and immunologic reactions against these proteins remain largely unknown. Understanding the structure of SARS CoV-2 proteins and demonstration of similarity with human proteins are crucial to predict an autoimmune response associated with immunity against host proteins and its clinical manifestations as well as possible adverse effects of vaccination.

Lupus retinopathy: epidemiology and risk factors.

Lupus retinopathy is a clinical manifestation of systemic lupus erythematosus in the visual system. It is generally asymptomatic; however, it can become a threatening condition. It is closely associated with the inflammatory activity and higher mortality of systemic lupus erythematosus. Lupus retinopathy has several different clinical presentations, such as lupus microangiopathy, vascular occlusion, vasculitis, hypertensive retinopathy associated with lupus nephritis, and autoimmune retinopathy. Although the prevalence and associated factors of lupus retinopathy have been well defined in some parts of the world, there are no data from Latin America, including Brazil. As lupus retinopathy is generally asymptomatic, without a routine fundoscopy, it has been probably underestimated. This review is intended to discuss the epidemiology and risk factors of lupus retinopathy.

Autoimmune retinopathy: findings and limitations from optical coherence tomography angiography

Background and objectiveTo report novel findings and limitations from optical coherence tomography angiography (OCTA) in the evaluation of autoimmune retinopathy (AIR).Study designWe retrospectively reviewed features of five patients diagnosed with AIR and five controls. OCTA scans were obtained and manually segmented to provide accurate measurements of foveal avascular zone (FAZ), vessel density, and retinal thickness at different levels.ResultsThe total retina and superficial vessel density throughout the whole scan were similar between AIR and controls (p = 0.14 and p = 0.11), whereas deep vessel density was decreased in AIR compared controls (p = 0.02). Decreased vessel density was most pronounced in the parafoveal and perifoveal areas (p = 0.01 and p = 0.01). AIR patients also had reduction of total retinal thickness in the perifoveal zone (p = 0.03), corresponding to outer retinal thinning (p = 0.001).ConclusionThis small series shows that AIR patients have reduced deep vessel density, particularly in the parafoveal and perifoveal regions and a decrease in macular thickness. These findings show correlation with the classic “flying saucer” sign seen on OCT.

Diagnosis and treatment of autoimmune retinopathy

: Autoimmune retinopathy (AIR) refers to both paraneoplastic and non-paraneoplastic forms of a rare, acquired retinal degeneration thought to be mediated by the production of antiretinal antibodies. However, the mechanisms underlying AIR pathogenesis are incompletely understood, and it remains a diagnosis of exclusion given the lack of definitive testing as well as its protean clinical presentation. This review summarizes the current literature on the epidemiology, diagnosis, and management of AIR, with a focus on non-paraneoplastic disease and the potential role of immunomodulatory therapy. A recent expert consensus statement on diagnosis and management of non-paraneoplastic AIR served as a framework for interpreting the limited data available, a process that was complicated by the small sample sizes, heterogeneity, and retrospective nature of these studies. Additional work is needed to characterize AIR patients on the basis of cytokine and immunogenetic profiling; to establish the pathogenicity of antiretinal antibodies; and to standardize treatment regimens as well as assessment of clinical outcomes.

Rituximab for autoimmune retinopathy: Results of a Phase I/II clinical trial.

PURPOSE:This prospective study evaluates whether rituximab is a safe and potentially effective treatment for nonparaneoplastic autoimmune retinopathy (npAIR).MATERIALS AND METHODS:Five npAIR patients were enrolled in a Phase I/II, prospective, nonrandomized, open-label, single-center study. All patients received a cycle of 1000 mg intravenous rituximab at weeks 0 and 2, with a second cycle of rituximab 6 to 9 months later. Clinical evaluation was performed at baseline, 6 and 12 weeks after each rituximab cycle, and then every 3 months for a total duration of 18 months. The primary outcome for this study was treatment success based on visual field and full-field electroretinography at 6 months. The secondary outcomes included treatment success at months 12 and 18, drug-related adverse events, changes in visual symptoms, and changes in quality of life.RESULTS:Two patients met criteria for treatment success: one based solely on electroretinography and the other based solely on visual field area, but treatment success was not sustained. Clinical response over the course of the 18-month study showed disease stabilization in three patients and treatment failure in two patients. There were no severe drug-related adverse events.CONCLUSION:This is the first clinical trial prospectively evaluating the effect of rituximab in npAIR and, although rituximab was well tolerated, there was no clear-cut clinical improvement conferred by B cell depletion with rituximab.

Correlation of Immunological Markers with Disease and Clinical Outcome Measures in Patients with Autoimmune Retinopathy.

PurposeTo determine if immunological markers (1) are significantly different between autoimmune retinopathy (AIR) patients and controls and (2) correlate with disease progression in AIR patients.MethodsWe enrolled patients with a possible AIR diagnosis, as well as control participants without eye disease, autoimmunity, or cancer. Immunological markers were tested in all participants. In addition, AIR patients had up to three blood draws for testing over their disease course. For AIR patients, clinical measures, including visual acuity (VA) and Goldmann visual field (GVF) area, were recorded at each draw. We used the Mann–Whitney U test to compare the immunological markers between AIR patients and controls. We used multilevel mixed-effect regression to investigate the correlation between markers and clinical parameters over time in AIR patients.ResultsSeventeen patients with AIR and 14 controls were included. AIR patients had a higher percent of monocytes (Z = 3.076, P = 0.002). An increase in immunoglobulin G against recoverin was correlated with a VA decrease (β = 0.0044, P < 0.0001). An increase in monocyte proportion was correlated with a decrease in GVF area (β = −7.27, P = 0.0021). Several markers of B-cell depletion were correlated with GVF improvement.ConclusionsMonocytes may play a role in AIR pathophysiology and be a disease activity marker. B-cell depletion markers correlated with clinical parameter improvement, particularly GVF.Translational RelevanceThis work elucidates immunologic markers that may improve the accuracy of diagnosis and treatment of AIR.

Autoimmune retinopathy associated with monoclonal gammopathy of undetermined significance: a case report

BackgroundMonoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia and precursor to multiple myeloma. It has known ocular manifestations, but has not previously been shown to have an association with autoimmune retinopathy.Case presentationA 57 year-old female presented with 1 year of progressive, bilateral, peripheral vision loss, photopsias, and nyctalopia. Her fundus examination and extensive ancillary testing were concerning for hereditary versus autoimmune retinopathy. The patient was found to have anti-retinal antibodies against carbonic anhydrase II and enolase proteins with a negative genetic retinal dystrophy panel. Malignancy work-up was negative, but the patient was diagnosed with MGUS, a premalignant condition. The patient was treated with immunosuppressive therapies, with rituximab demonstrating the most robust therapeutic response with respect to patient symptoms and ophthalmic testing.ConclusionsMGUS should be considered as a potential etiology of autoimmune retinopathy in patients without other autoimmune or malignant disease processes. Immunosuppressive therapy may be helpful in limiting disease progression, with rituximab showing efficacy in retinopathy refractory to other agents.

Non-paraneoplastic autoimmune retinopathy that developed in fellow eye 10\u2009years after onset in first eye: a case report

BackgroundEvidence-based criteria for the treatment of autoimmune retinopathy (AIR) have not been established. The pathology and clinical features of each antibody causing AIR, and its long-term course are still undetermined. We report our findings in a case of non-paraneoplastic AIR (npAIR) that developed in the fellow eye 10 years after the onset in the first eye.Case presentationOur patient had photophobia in both eyes and a rapidly progressing visual field defect in his right eye at the initial examination. He was diagnosed with non-paraneoplastic AIR based on the clinical findings and immunoblot analyses for anti-retinal antibodies, and he was treated with steroids. Ten years later, a visual field defect developed in the fellow eye, and a diagnosis of npAIR was made. Immunoblot analyses were positive for anti-α-enolase antibodies. He was treated with steroids, immunosuppressants, and plasma exchange. However, the response to the treatment was poor and both eyes eventually became blind.ConclusionsAs best we know, this is the first case report of npAIR that developed in the fellow eye over 10 years after the development in the first eye. Long-term follow-up and a search for tumor lesions are necessary in cases of npAIR. Further understanding of the long-term course of AIR can contribute to an understanding of the pathology and treatment of npAIR.

Phase Ib trial of pembrolizumab and XL888 in patients with advanced gastrointestinal malignancies: Results of the dose-escalation phase.

830 Background: XL888 is a selective inhibitor of heat shock protein 90 (HSP90). It modulates several oncogenic signaling pathways, and the tumor microenvironment. In preclinical models, XL888 potentiates efficacy of PD-1 inhibition. We report the results of the dose escalation (DE) portion of a phase Ib trial of combined XL888 and pembrolizumab (P) in advanced gastrointestinal adenocarcinomas. Methods: XL888 was administered orally (PO) in three dose levels of 45 (DL1), 90 (DL2), 60 (only if DLT on DL2) mg twice weekly with P 200 mg IV on day 1, in 21-day cycles. Eligible patients included stage IV or locally advanced unresectable gastrointestinal adenocarcinomas with at least one prior therapy (patients with colorectal (CRC) adenocarcinoma must have received oxaliplatin, irinotecan, and fluoropyrimidine), age ≥18 years, ECOG PS 0-1, adequate organ function, no prior anti-PD-1 or anti-PD-L1 agent. The primary endpoint was recommended phase II dose (RP2D), while secondary endpoints included safety and tolerability. Pre-treatment and on-treatment correlative peripheral blood specimens were collected. Results: A total of 14 patients were enrolled in the DE phase. 9 male, median age 66.5. Diagnoses included CRC (6), pancreatic adenocarcinoma (5), biliary tract cancer (1), ampullary (1), and duodenal (1). Two patients were ineligible for assessing the primary endpoint (DL2) due to biliary stent obstruction and sepsis. One DLT (grade 3 autoimmune hepatitis) was observed on DL2. We enrolled three patients on DL3. Five additional patients were subsequently enrolled on DL2 with no additional DLT. Three patients (1 duodenal, 2 CRC) had prolonged stable disease (6, 9 and 15 cycles). The most common treatment-related toxicities included autoimmune hepatitis (G3; n = 1), retinopathy (G2; n = 2), nausea (G2; n = 1), constipation (G2; n = 1), and diarrhea (G2; n = 3). Conclusions: The XL888 and pembrolizumab combination had an acceptable safety profile and the RP2D of XL888 was 90 mg twice weekly combined with P 200 mg, every 3 weeks. The dose expansion portion and a robust series of immunologic correlative laboratory studies for this study is ongoing. Clinical trial information: NCT03095781.

An update on autoimmune retinopathy.

Autoimmune retinopathy (AIR) refers to a group of rare autoimmune retinal degenerative diseases presumably caused by cross-reactivity of serum autoantibodies against retinal antigens. The pathogenesis of AIR remains largely presumptive and there are a significant number of antiretinal antibodies that have been detected in association with AIR. The diagnosis of AIR is largely based on the demonstration of antiretinal antibodies in the serum along with suggestive clinical features and ancillary investigations. A high index of suspicion along with early diagnosis and treatment may play a critical role to lower the risk of irreversible immunological damage to the retinal cells in these patients. A multi-disciplinary approach for complete management and evaluation is helpful in such conditions. Various therapeutic options have been described for the treatment of AIR, though there is no consensus on standard treatment protocol.

RECONSTITUTION OF THE ELLIPSOID ZONE WITH TOCILIZUMAB IN AUTOIMMUNE RETINOPATHY

To demonstrate improvement and stabilization of retinal findings, including recalcitrant cystoid macular edema, in a patient with nonparaneoplastic autoimmune retinopathy after treatment with tocilizumab, a humanized monoclonal antibody against soluble and membrane-bound IL-6 receptor. Observational case report. A 46-year-old woman was diagnosed with nonparaneoplastic autoimmune retinopathy and followed over 4 years on various immunosuppressive medications with worsening disease and recalcitrant cystoid macular edema. This report describes the rapid improvement and stabilization of her ocular disease once tocilizumab was initiated. Tocilizumab, a monoclonal antibody against the IL-6 receptor, was initiated at a dose of 8 mg/kg every 4 weeks. Cystoid macular edema was significantly decreased after just two infusions and nearly resolved after five infusions. Ellipsoid zone and outer retinal integrity also improved on optical coherence tomography. The patient tolerated the medication with limited side effects. Long-term immunosuppression is the cornerstone of treatment for nonparaneoplastic autoimmune retinopathy, although success is highly variable. We report a case treated with tocilizumab with dramatic improvement in refractory macular edema and reconstitution of the ellipsoid zone on optical coherence tomography in a patient with nonparaneoplastic autoimmune retinopathy. This case highlights the potential role of treatment with an IL-6 inhibitor in autoimmune retinopathy though further studies are needed.

Paraneoplastic causes of vision loss

AbstractParaneoplastic occular disorders are clinical syndromes resulting from nonmetastatic systemic effects of underlying cancers. While not fully elucidated the underlying mechanism is presumed to be a cross reaction of the immune reaction to the underlying cancer that attaches normal host tissue. This cross reaction can happen in a variety of occular tissues resulting in dysfunction of the retina, optic nerve and tear film and extraocular muscles. (1‐3). The lists of cancers and associated antibodies is constantly growing but, in many cases, the clinical phenotype is very similar. Cancer associated retinopathy (CAR) for example is associated with several antibodies including anti‐recoverin, anti‐alpha enolase, anti‐transducin, and anti‐carbonic anhydrase(2, 3). Each of these antibodies have been associated with a distinct cancer including skin, genital and small cell lung cancer (SCLC). CAR causes a slowly progressive asymmetric vision loss due to damage to retinal ganglion cells and bipolar cells which can result in optic nerve pallor. Melanoma associated retinopathy (MAR), similarly can present with nyctalopia, photopsia’s and loss of peripheral vision. The antibodies associated with MAR; anti‐transducin, anti‐rhodopsin and anti‐arrestin typically attack the on bipolar system. As with CAR the visual dysfunction can predate the discovery of the cancer. Conversely, autoimmune related retinopathy and optic neuropathy occurs without an underlying cancer and is associated with anti‐GAD and anti‐ anti‐collapsin‐responsive mediator protein‐5 (CRMP‐5) antibodies(2). In all three cases electroretinograms are key to making the diagnosis as the objective clinical examination can be normal. Electroretinograms are key to distinguishing retinal dysfunction which can cause an optic neuropathy from a paraneoplastic optic neuropathy (PON). The classical antibody in PON is. CRMP‐5 is associated with SCLC and thymoma and can produce optic disc edema with subsequent atrophy. The treatment and management of occular paraneoplastic disorders requires appropriate investigations to look for an underlying cancer. Knowing the specific antibody associated with the disorder can be helpful in this regard and in some cases a panel of antibody tests is appropriate in the right clinical context(4). Treatment of the underlying cancer can, in some cases, can lead to a resolution of the clinical symptoms. Symptom control can also be accomplished using immunosuppression with steroids or IVIG and in some cases plasmapheresis has been useful(4, 5).References Grewal DS, Fishman GA, Jampol LM. Autoimmune retinopathy and antiretinal antibodies: a review. Retina. 2014;34(5):827–45. Bataller L, Dalmau J. Neuro‐ophthalmology and paraneoplastic syndromes. Current opinion in neurology. 2004;17(1):3–8. Rahimy E, Sarraf D. Paraneoplastic and non‐paraneoplastic retinopathy and optic neuropathy: evaluation and management. Survey of ophthalmology. 2013;58(5):430–58. Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clin Proc. 2010;85(9):838–54. Damek DM. Paraneoplastic Retinopathy/Optic Neuropathy. Current treatment options in neurology. 2005;7(1):57–67.

Occurrence of major anti-retinal autoantibodies associated with paraneoplastic autoimmune retinopathy

Autoantibodies (AAbs) against retinal antigens can be found in patients with cancer and unexplained vision loss unrelated to the cancer metastasis. Cancer-associated retinopathy (CAR) is a rare paraneoplastic visual syndrome mediated by AAbs. Our goal was to determine whether CAR patients with different malignancies have a specific AAb or repertoire of AAbs that could serve as biomarkers for retinal disease. We found AAbs against 12 confirmed retinal antigens, with α-enolase being the most frequently recognized. The significant finding of the study was a high incidence of anti-aldolase AAbs in colon-CAR, anti-CAII in prostate-CAR, and anti-arrestin in skin melanoma patients thus these AAbs could serve as biomarkers in the context of clinical presentation and could support the diagnosis of CAR. However, a lack of AAb restriction to any one antigenic protein or to one retinal cellular location makes screening for a CAR biomarker challenging.