Antiretinal Antibodies Research Articles

Controversies between retinal dystrophies and uveitis – the point of view of the uveitis specialist: does retinal antibody detection help?

SummaryMany diseases, presumed to be mediated by autoimmune mechanisms, may have clinical picture suggestive of retinal dystrophies. The paradigm of such cases is illustrated by cancer associated retinopathies. However the spectrum of antibody mediated retinopathy is expanding and non neoplastic forms are grouped under the name autoimmune retinopathy (AIR). However, the difficulties to demonstrate the presence of retinal antibodies, as well as their presence in control and retinal dystrophy patients render the diagnosis very challenging. In this talk, we will, through case reports, illustrate the potential usefulness and pitfalls of antiretinal antibody search in the management of such cases.

Introducing MARCo: Histoserological Findings of a Multi-Organic Paraneoplastic Syndrome in Cutaneous Melanoma Patients.

IntroductionCutaneous melanoma (CM) is an aggressive skin cancer entity, causing most skin cancer-related deaths. Autoimmune disorders have been described as potential paraneoplastic complications. The purpose of this study was to elucidate the possibility of a combinatory paraneoplastic affection of the retina and cochlea in patients with CM.MethodsSera samples from CM patients were used for indirect immunofluorescence on histological retinal and cochlear sections. Furthermore, the serum specimen of a patient with symptomatic affection of both organs was analyzed by multiplex ELISA (enzyme-linked immunosorbent assay) for various cytokines including CD163 (cluster of differentiation 163).ResultsEleven patients were diagnosed with CM. Autoantibodies against structures of the inner ear were confirmed in all patients who were tested positive for antiretinal antibodies as well. CD163 was significantly elevated in the double-symptomatic patient, who developed metastatic disease.ConclusionParaneoplastic disease of CM can affect more than one organ and this affect may be correlated with the individual prognosis. Therefore, a thorough anamnesis is needed to avoid missing potential symptoms.

Consensus on the Diagnosis and Management of Nonparaneoplastic Autoimmune Retinopathy Using a Modified Delphi Approach

To develop diagnostic criteria for nonparaneoplastic autoimmune retinopathy (AIR) through expert panel consensus and to examine treatment patterns among clinical experts. Modified Delphi process. A survey of uveitis specialists in the American Uveitis Society, a face-to-face meeting (AIR Workshop) held at the National Eye Institute, and 2 iterations of expert panel surveys were used in a modified Delphi process. The expert panel consisted of 17 experts, including uveitis specialists and researchers with expertise in antiretinal antibody detection. Supermajority consensus was used and defined as 75% of experts in agreement. There was unanimous agreement among experts regarding the categorization of autoimmune retinopathies as nonparaneoplastic and paraneoplastic, including cancer-associated retinopathy and melanoma-associated retinopathy. Diagnostic criteria and tests essential to the diagnosis of nonparaneoplastic AIR and multiple supportive criteria reached consensus. For treatment, experts agreed that corticosteroids and conventional immunosuppressives should be used (prescribed) as first- or second-line treatments, though a consensus agreed that biologics and intravenous immunoglobulin were considered appropriate in the treatment of nonparaneoplastic AIR patients regardless of the stage of disease. Experts agreed that more evidence is needed to treat nonparaneoplastic AIR patients with long-term immunomodulatory therapy and that there is enough equipoise to justify randomized, placebo-controlled trials to determine if nonparaneoplastic AIR patients should be treated with long-term immunomodulatory therapy. Regarding antiretinal antibody detection, consensus agreed that a standardized assay system is needed to detect serum antiretinal antibodies. Consensus agreed that an ideal assay should have a 2-tier design and that Western blot and immunohistochemistry should be the methods used to identify antiretinal antibodies. Consensus was achieved using a modified Delphi process to develop diagnostic criteria for nonparaneoplastic AIR. There is enough equipoise to justify randomized, placebo-controlled trials to determine whether patients with nonparaneoplastic AIR should be treated with long-term immunomodulatory therapy. Efforts to develop a standardized 2-tier assay system for the detection of antiretinal antibodies have been initiated as a result of this study.

Prevalence and clinical impact of antiretinal antibodies in uveitis.

To determine the prevalence of serum antiretinal antibodies (ARAs) among patients with uveitis and establish their clinical relevance. This prospective study assessed the presence of ARAs by indirect immunofluorescence (IIF) using primate retina in 126 patients with uveitis and 60 healthy controls. Clinical data of uveitis patients were collected from medical charts and included the classification of uveitis, cause of uveitis or its association with systemic disease, stage and activity of uveitis and specific retinal features. Correlations between the presence of specific ARAs and various clinical characteristics were analysed. The presence of ARAs was observed in 49 of 104 (47%) of patients with uveitis and in 10 of 59 (17%) of healthy controls (p < 0.001). Staining of the nuclear layers or the photoreceptors were both more often observed in patients with uveitis compared to healthy controls (p = 0.002 and p = 0.018, respectively). No specific associations were found between the presence of serum ARAs and various clinical characteristics. Serum ARAs were more frequent in patients with uveitis compared to healthy controls, but their clinical role remains elusive. The assessment of intraocular production of specific ARAs may provide further insight into the role of ocular autoantibodies in diverse uveitis entities.

Positive Auto-Antibody Activity With Retina and Optic Nerve in Smokers and Non-Smokers: The Controversy Continues.

Auto-antibodies assist with the diagnosis of ocular paraneoplastic syndromes and autoimmune ocular conditions; however, the frequency of positive test results as a possible precursor to future disease is unknown. The frequency of positive antibodies in heavy smokers who may be at risk for autoimmune-related retinopathy and optic neuropathy was evaluated. Serum antibody activity was evaluated through the use of Western blot reactions from pig retina and optic nerve extract. Fifty-one patients were included: 35 patients were smokers (average: 40.9 pack-year history) and 26 patients had no past smoking history. None of the patients had any visual complaints or known eye disease. Of the patients studied, 76.5% (39 patients: 18 smokers, 21 non-smokers) had positive antiretinal antibodies, and 19.6% (10 patients: 3 smokers, 7 non-smokers) had positive antioptic nerve antibodies. Anti-retinal antibodies were seen in a majority of randomly selected patients with and without a past smoking history. Anti-optic nerve bodies were less common, but more prevalent in those who never smoked. The specificity of these antibodies remains greatly uncertain and clinical correlation is warranted.

The Uncertainty Regarding Antiretinal Antibodies.

The Uncertainty Regarding Antiretinal Antibodies.

Serous Retinopathy Associated with Mitogen-Activated Protein Kinase Kinase Inhibition (Binimetinib) for Metastatic Cutaneous and Uveal Melanoma

To analyze the clinical characteristics of a serous retinopathy associated with mitogen-activated protein kinase kinase (MEK) inhibition with binimetinib treatment for metastatic cutaneous melanoma (CM) and uveal melanoma (UM), and to determine possible pathogenetic mechanisms that may lead to this retinopathy. Prospective observational, cohort-based, cross-sectional study. Thirty CM patients and 5 UM patients treated with the MEK inhibitor binimetinib (CM) or a combination of binimetinib and the protein kinase C inhibitor sotrastaurin (UM). Extensive ophthalmic examination was performed, including Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, applanation tonometry, slit-lamp examination, indirect ophthalmoscopy, digital color fundus photography, and optical coherence tomography (OCT). In selected cases, additional examinations were performed, including visual field testing and electro-oculography (EOG). Blood samples were obtained from 3 CM patients and 3 UM patients to analyze the presence of autoantibodies against retinal and retinal pigment epithelium (RPE) proteins. Visual symptoms, visual acuity, fundus appearance, characteristics on OCT, fundus autofluorescence (FAF), and EOG. Six CM patients (20%) and 2 UM patients (40%) reported visual symptoms during the study. The median time to the onset of symptoms, which were all mild and transient, was 3.5 days (range, <1 hour to 3 weeks). On OCT, subretinal fluid (SRF) was detected in 77% of CM patients and 60% of UM patients. In the 26 patients with SRF, the fovea was affected in 85%. After the start of the medication, an EOG was performed in 19 eyes of 11 patients; 16 of these eyes (84%) developed SRF on OCT. Fifteen of these eyes (94%) showed an abnormal Arden ratio (<1.65). A broad pattern of anti-retinal antibodies was found in 3 CM patients and 2 UM patients tested, whereas anti-RPE antibodies were detected in all 6 tested patients. A time-dependent and reversible serous retinopathy can develop both in patients with metastatic CM and UM treated with binimetinib. A minority of patients develop visual symptoms, which are generally mild and transient. A cause of binimetinib-associated serous retinopathy may be toxicity of medication, but autoantibodies also may be involved.

Retinal degeneration in autoimmune polyglandular syndrome type 1: a case series

BackgroundAutoimmune polyglandular syndrome type 1 (APS1) is a rare autosomal recessive disorder due to mutations in the AIRE gene.AimTo report the ocular features and characterise the retinal phenotype in molecularly...

Circulating anti-retinal antibodies in response to anti-angiogenic therapy in exudative age-related macular degeneration.

To determine changes in anti-retinal antibodies (ARAs) during anti-VEGF therapy in patients with exudative age-related macular degeneration (AMD) and to assess the correlations between ARAs and disease activity. The study comprised 98 patients treated with intravitreal bevacizumab. The ophthalmic examination included best corrected visual acuity (BCVA), slit lamp biomicroscopy, fundoscopy, fluorescein angiography (FA), and optical coherence tomography (OCT). Serum ARAs levels were assessed by indirect immunofluorescence (IIF) on normal monkey retina substrate. These studies were repeated at 4 week intervals within 8 months of a follow-up. The sera of 50 sex- and age-matched healthy subjects were used as controls. At baseline examination, 94 (95.5%) of the 98 patients were positive for ARAs. The ARAs titres were significantly higher (p = 0.0000) than in controls. A positive correlation was found between titres of ARAs and the diameter of choroidal neovascularization (CNV) as measured by FA (p = 0.0000), and central retinal thickness (CRT) assessed by OCT (p = 0.0000). A positive correlation was also found between the diameter of CNV, CRT and the complexity of circulating ARAs. Following treatment all patients demonstrated significant decrease in ARAs levels as well as improvement of BCVA, reduction of subretinal fluid on OCT and decreased leakage on FA. Changes in serum ARAs levels occurred in parallel with clinical outcomes of anti-VEGF therapy. Treatment reduced serum levels of ARAs, with the greatest reduction occurring during the 'loading' phase. This study demonstrated that ARAs may act as a serum biomarker of the efficacy of anti-VEGF therapy.

AUTOIMMUNE RETINOPATHY AND ANTIRETINAL ANTIBODIES

To review the current state for diagnosis and management of autoimmune retinopathy. A review of the literature was performed, encompassing autoimmune retinopathy including paraneoplastic retinopathy (cancer-associated retinopathy, melanoma-associated retinopathy, and bilateral diffuse uveal melanocytic proliferation) and non-paraneoplastic autoimmune retinopathy. Based on this review, current principles and techniques for diagnosis and the treatments reported for autoimmune retinopathy are discussed with the aim to clarify some of the confusion that exists regarding this complex entity. Autoimmune retinopathy encompasses a spectrum of retinal degeneration phenotypes. The clinical features, fundus characteristics, and electroretinogram findings for paraneoplastic and non-paraneoplastic retinopathy are reviewed. The different antiretinal antibodies reported in these entities are described. The diagnostic approaches for detecting these antiretinal antibodies and their limitations are covered. The treatments reported for autoimmune retinopathy and their outcomes are reviewed. Among the myriad of antiretinal antibodies reported, challenges persist in determining which antibodies are pathogenic and which are benign and what factors cause antiretinal antibodies to become pathologic. There also remain difficulties in the detection and accurate measurement of antiretinal antibodies, and the response to therapeutic intervention in autoimmune retinopathy is variable.

A case of paraneoplastic optic neuropathy and outer retinitis positive for autoantibodies against collapsin response mediator protein-5, recoverin, and α-enolase

BackgroundSpecific cross-reacting autoimmunity against recoverin or collapsin response mediator protein (CRMP)-5 is known to cause cancer-associated retinopathy or paraneoplastic optic neuropathy, respectively. We report a rare case with small cell lung carcinoma developing bilateral neuroretinitis and unilateral focal outer retinitis positive for these antibodies.Case presentationA 67-year-old man developed bilateral neuroretinitis and foveal exudation in the right eye. Optical coherence tomography showed a dome-shaped hyperreflective lesion extending from inner nuclear layer to the photoreceptor layer at the fovea in the right eye. Single-flash electroretinography showed normal a-waves in both eyes and slightly reduced b-wave in the left eye. Results of serological screening tests for infection were within normal limits. The patient’s optic disc swelling and macular exudation rapidly improved after oral administration of prednisolone. Systemic screening detected lung small cell carcinoma and systemic chemotherapy was initiated. Immunoblot analyses using the patient’s serum detected autoantibodies against recoverin, CRMP-5, and α-enolase, but not carbonic anhydrase II. Neuroretinitis once resolved after almost remission of carcinoma on imaging but it recurred following the recurrence of carcinoma.ConclusionsThe development of neuroretinitis in this cancer patient with anti-retinal and anti-optic nerve antibodies depended largely on the cancer activity, suggesting the possible involvement of paraneoplastic mechanisms. Patients with paraneoplastic optic neuropathy and retinopathy are likely to develop autoimmune responses against several antigens, thus leading to various ophthalmic involvements.

Autoimmune retinopathy

Autoimmune retinopathy (AIR) is an immune-mediated disorder characterized by progressive visual loss, abnormal electroretinographic and visual field findings in the presence of circulating anti-retinal antibodies. This review highlights advances made toward understanding the pathophysiology, clinical manifestations, and trends in the management of AIR. The pathophysiology of AIR is likely antibody-mediated. AIR serum autoantibodies are variable in their size and retinal tissue they target and can also be present in healthy controls and multiple autoimmune diseases. Rarely, AIR may be associated with dysregulated self-tolerance mechanisms in the thymus. Despite progress in research, our understanding of AIR remains incomplete. Lack of standardized methods for anti-retinal antibody testing continues to challenge the interpretation of seropositivity. Conventional immunosuppressives have been further studied, and promising immunomodulatory therapies, such as targeted B-cell therapy, have been introduced. Newer imaging modalities such as fundus autofluorescence and spectral domain optical coherence tomography may be helpful in diagnosis, monitoring progression of disease and response to treatment. AIR is a rare but vision-threatening disease whose pathogenesis is poorly defined. Lack of standardized clinical or laboratory criteria further complicates the diagnosis and management. Despite recent progress, further basic science research into the autoimmune process is needed. Prospective controlled clinical trials with immunomodulatory therapy can help define future treatment paradigms.

Autoimmune retinopathy associated with carcinoid tumour of the small bowel

Cancer associated retinopathy (CAR) is an immune mediated paraneoplastic condition associated with vision loss. It has been associated with a variety of systemic malignancies. The primary clinical presentation is rapid, progressive vision loss. Rod and cone dysfunction can cause other associated symptoms, such as nyctalopia. Electrophysiological testing and detection of anti-retinal antibodies are used to confirm the diagnosis. To our knowledge we describe the first patient with CAR associated with a carcinoid tumour of the gastrointestinal system. Auto-antibodies against alpha enolase and carbonic anhydrase II were detected with western blotting. Electroretinogram findings were consistent with rod and cone dysfunction.

Autoimmune Retinopathy

To provide a detailed review of current clinical guidelines for the diagnosis, work-up and treatment of autoimmune retinopathy and to preview briefly possible future therapies. Perspective based on literature review and clinical expertise. Interpretation of current literature, relying on the authors' clinical experience. Autoimmune retinopathy is a rare immunologic disease characterized by the presence of circulating antiretinal antibodies along with electroretinographic and visual field abnormalities. An ophthalmic examination can be normal or show minimal findings. The diagnosis of autoimmune retinopathy is made difficult by diagnostic criteria that are both limited and nonstandardized. Currently, the diagnosis is made based on the demonstration of serum antiretinal antibodies and the presence of clinical manifestations (including abnormal electroretinographic findings). The mere presence of these antibodies is not diagnostic. Lack of an accepted gold standard for antiretinal antibodies detection and poor interlaboratory concordance make the diagnosis challenging. There are anecdotal reports of immunosuppressive therapy in autoimmune retinopathy; however, the response to treatment is variable, with more favorable results achieved in paraneoplastic retinopathy, particularly cancer-associated retinopathy, with a combination of chemotherapy and immunosuppression. Whether an earlier attempt to treat nonparaneoplastic autoimmune retinopathy would be more beneficial is unknown. Early treatment attempts are limited by lack of sensitive and specific assays and definitive clinical criteria. Little is known about the clinical course, prognosis and treatment of autoimmune retinopathy. Additional studies should examine the specificity and pathogenicity of antiretinal antibodies and screen for biomarkers, and they should be conducted concurrently with studies seeking to identify appropriate treatment.

Detection of autoantibodies against heat shock proteins and collapsin response mediator proteins in autoimmune retinopathy

BackgroundAutoimmune 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.MethodsHuman retinal proteins were separated by SDS-PAGE and 2D gel electrophoresis (2-DE) and sera from AR patients with and without cancer were used to identify immunoreactive proteins by Western blotting. Proteins were identified following separation by electrophoresis, Coomassie staining using in-gel trypsin digestion and mass spectrometric analysis. Circulating serum hsp60 and anti-hsp60 antibody levels were determined by quantitative ELISA.ResultsRetrospective evaluation of 819 patients with anti-retinal AAbs showed that 29% patients had AAbs targeted proteins between 60-70-kDa. Shotgun mass spectrometry of human retinal proteins present in 1D-gel found 66 species within this range. To identify the immunoreactive proteins, we performed Western blots of 2-DE gels and showed a group of heat shock proteins (hsps), including hsp60 and CRMP proteins that were frequently recognized by AR patient AAbs, irrespective of cancer status. These results were validated by immunostaining of purified hsp60 and CRMP2 proteins. ELISA results revealed that patients with AR and CAR had significantly increased levels of serum anti-hsp60 antibodies compared to control healthy subjects (p < 0.0001). However, circulating hsp60 protein was not significantly elevated in sera of either patient group.ConclusionsDifferent anti-retinal antibodies frequently co-exist in a single patient, creating antibody-arrays related to the syndrome. Hsps and CRMP-2 are newly identified autoantigens in AR. A frequent co-association of anti-hsp antibodies with other anti-retinal AAbs may augment pathogenic processes, leading to retinal degeneration.

Unilateral intravitreal dexamethazone implant for bilateral retinitis pigmentosa-related macular edema

Dear Editor, I would like to congratulate Srour et al. for their case series about the treatment of macular edema (ME) secondary to retinitis pigmentosa by intravitreal dexamethasone implant (Ozurdex) (DEX implant) [1]. Retinal pigmentosa (RP) is a group of inherited retinal degenerative diseases caused by several gene abnormalities. The first lesion is peripheral, and the central vision of RP patients is relatively preserved. However, when ME occurs in these patients, central vision is often impaired. The ME could be caused by circulating antiretinal antibodies; this suggests that an autoimmune process may be implicated in the formation ofME in RP [2]. Sustained chronic inflammatory reaction may contribute to the pathogenesis of retinal degeneration in rd10 mice, suggesting there is ocular inflammatory reaction in patients with RP [3]. In this case, a treatment by corticosteroids could be efficient. Indeed, Srour et al. report the efficacy of intravitreal dexamethasone implant for macular edema secondary to retinitis pigmentosa on three patients [1]. Only one had bilateral ME and was treated in each eye. For these three patients treated by DEX implant for ME with RP, the decrease of retina thickness was important, but there was recurrence for two patients. Recently, Saatchi reported the treatment of a bilateral ME by an intravitreal dexamethasone implant in each eye too [4]. We would like to report our original experience [5]. A 22-year old man diagnosed of RP was referred to our department because he had bilateral ME and needed to have good vision to be successful in school (Fig. 2a). Carbonic anhydrase inhibitors (acetazolamide, 500mg daily) and brinzolamide (one drop in each eye twice a day) were not effective. We decided to inject intravitreal Ozurdex (0.7 dexamethasone implant). It was administered without complications on the right eye according to standard procedure (Fig. 1). Spectralis SD-OCT revealed reduction of the ME for both eyes, even in the first week (Fig. 2a and b). On the first month follow-up, best-corrected visual acuity (BCVA) had improved from 20/40 to 20/30 for the right eye and from 20/40 to 20/20 for the left eye, while the retina thickness had decreased from 538 μm to 294 μm for the right eye and from 428 μm to 319 μm for the left eye (Fig. 2c). No cataract progression was observed during the study period. In the case of bilateral ME, Dex implant could provide anatomic and functional patient improvements for both eyes in a unilateral injection. It could be interesting for diseases with bilateral ME. We advise waiting for the efficacy of a first

Anti-Retinal Antibodies in Patients With Macular Telangiectasia Type 2

Macular telangiectasia type 2 (MacTel-2) is a retinal disease that can cause loss of central vision. To gain better understanding of the etiology and pathogenesis of MacTel-2, we investigated antigens that prompt the generation of retinal autoantibodies in the serum of patients with MacTel-2. We screened for the presence of retinal autoantibodies in 45 serum samples collected from patients with MacTel-2 and 58 serum samples from healthy control subjects by Western blot. We then isolated and identified three retinal proteins that are putative targets of three of the most frequently detected autoantibodies in the serum of patients with MacTel-2 using chromatographic fractionation and liquid chromatography coupled to tandem mass spectrometry. We also validated the retinal location of the three antigens by immunohistochemisty using MacTel-2 sera as primary antibodies and commercial antibodies. Retinal autoantibodies were detected in a significantly higher proportion of patients with MacTel-2 than in controls (31 of 45 [69%] vs. 9 of 58 [16%], P < 0.0001). The three antigens that were targeted by the most frequently detected MacTel-2 autoantibodies were identified as glycogen debranching enzyme (hereafter AGL, named for the gene symbol AGL), retinol-binding protein 3 (RBP3), and creatine kinase type B (CK-B); autoantibodies against these antigens were found in four, eleven, and nine MacTel-2 serum samples, respectively. We found that most patients with MacTel-2 possess retinal autoantibodies, the most prevalent of which were directed against AGL, RBP3, and CK-B. The localization of retinal proteins bound by AGL, RBP3, and CK-B autoantibodies is consistent with their putative physiological functions. These findings provide potentially novel mechanisms for the etiology and pathogenesis of MacTel-2.

Clinical and Immunological Characterization of Paraneoplastic Retinopathy

To report the clinical and immunological characterization of paraneoplastic retinopathy (PR) and to investigate the association between spectral-domain optical coherence tomography (SDOCT) findings and the targets of autoantibodies in PR. We retrospectively enrolled eight patients (age range, 57-85 years; four men and four women) suspected of having PR. All patients underwent comprehensive ophthalmic examinations, including best-corrected visual acuity (BCVA) measurement, slitlamp examinations, kinetic visual field testing with Goldmann perimetry, electroretinography (ERG), fundus photography, fluorescein angiography, fundus autofluorescence (FAF), SDOCT, and serum sample tests (Western blot analysis and immunohistochemistry [IHC]). Three patients had a history of malignant tumors, and four patients were newly diagnosed as having neoplastic tumors (small cell lung carcinoma [SCLC], thymoma, pancreatic neuroendocrine neoplasm, and colon cancer). Another de novo malignancy (SCLC) was detected in a patient with a history of malignancy (bladder cancer and liposarcoma). The BCVA in these patients ranged from hand motion to 1.5. Goldmann perimetry revealed island, ring-shaped, concentric, or central scotoma. All patients showed nonrecordable or reduced amplitude results on ERG. Fluorescein leakage was detected in five patients. Hyperautofluorescence and/or hypoautofluorescence on FAF was detected in six patients. The serum sample tests identified anti-retinal antibodies in all patients. Patients whose serum contained anti-photoreceptor or anti-retinal pigment epithelium antibody on IHC showed damage of the outer retina on SDOCT. In this case series, PR was associated with a variety of neoplasms and autoantibodies. Spectral-domain OCT can be used to characterize morphologic changes, and the changes were associated with the targets of autoantibodies.

Upper hemiretinal occult retinopathy

AbstractPurpose To emphasize the significance of photopsias and positive scotomas as subjective indicators of occult retinopathy.Methods The patient’s depiction of his photopsias led to a diagnostic work‐up by white and red static and kinetic perimetry, OCT, and visual electrophysiology.Results Within the OD lower visual field our patient encountered a rapid loss of color vision. In dark environs, coloured photopsias showed up in this region, in bright environs, a positive black scotoma developped over time. Kinetic perimetry revealed a relative lower hemifield scotoma by white and an absolute one by red targets. On static perimetry, a distinct lower hemifield scotoma improved for white but persisted for red stimuli during 3 years of follow up. Retinal origin of the scotoma was proven by mf ERG. Serology for anti‐retinal antibodies remained negative. Difficult to detect by ophthalmoscopy, an affection of the OS / RPE layer in the corresponding fundus area was proven by SD OCT.Conclusion Coloured photopsias in dark, a black positive scotoma in bright envorons are salient symptoms of this upper hemifield occult retinopathy. OCT, visual fields and electrodiagnostic findings point towards a variant of AZOOR (acute zonal occult outer retinopathy).

A curious case of glaucoma?

An 84-year-old woman diagnosed with primary open-angle glaucoma was referred because her optic nerve appearance did not account for her visual field deficits. Further evaluation showed loss of color vision and rapid progression of visual field defects. Electroretinography revealed abnormal scotopic and photopic responses. Blood samples were positive for anti-retinal antibodies, but a malignancy work-up was negative, consistent with non-paraneoplastic autoimmune retinopathy.