Acute Zonal Occult Outer Retinopathy Research Articles

Diagnostic yield of an inherited retinal disease gene panel in retinopathy of unknown origin

Purpose: Evaluating the presence of class 3, 4 and 5 genetic variants in inherited retinal disease (IRD) genes in patients with retinopathy of unknown origin (RUO). Methods: Multicentric retrospective study of RUO cases diagnosed between January 2012 and February 2022. General and ophthalmological history, complete ophthalmological examination, anti-retinal antibodies and IRD gene panel results were analyzed in every patient. Four RUO categories were defined: non-paraneoplastic autoimmune retinopathy (npAIR), unilateral pigmentary retinopathy (UPR), asymmetrical pigmentary retinopathy (APR) and acute zonal occult outer retinopathy (AZOOR). Results: We included 12 patients (9 females) across these four RUO categories. Mean age at inclusion was 45.6 years (20 – 68 years). Seven patients demonstrated class 3 variants in IRD genes. Of these, 2 also demonstrated class 5 variants in other IRD genes. The remaining 5 patients had negative panel results. IRD gene panel analysis allowed diagnosis refinement in 1 (8.3%) npAIR patient in our RUO cohort. When considering the npAIR subpopulation only, a higher diagnostic yield of 20% (1/5 patients) was achieved. Conclusions: Every suspected npAIR patient should benefit from gene panel testing in order not to overlook undiagnosed IRDs. In contrast, UPR, APR and AZOOR subpopulations did not benefit from genetic analysis in this study.

A Case of an Acute Zonal Occult Outer Retinopathy Variant Characterized With an Insidious Peripheral Onset and Centripetal Progression

A Case of an Acute Zonal Occult Outer Retinopathy Variant Characterized With an Insidious Peripheral Onset and Centripetal Progression

Bilateral recurrent choroidal neovascularization in AZOOR

A 61-year-old man presented with recurrent bilateral peripapillary choroidal neovascularization (CNV), which was treated with intravitreal bevacizumab injections. Fundus autofluorescence revealed the typical acute zonal occult outer retinopathy (AZOOR) trizonal pattern, so the patient was started on immunosuppressive treatment with prednisone and methotrexate, and subsequently with mycophenolate mofetil due to recurrent inflammatory activity. While on immunosuppressive treatment, further CNV showing the “pitchfork sign” appeared in the right eye and required multiple bevacizumab injections due to persistent activity. The complication of CNV in AZOOR is very rare and treatment is a challenge. However, the combination of intravitreal anti-VEGF with immunosuppressive treatment could prevent the progression of the disease.

Clinical features and possible pathogenesis of multiple evanescent white dot syndrome with different retinal diseases and events: a narrative review.

Multiple evanescent white dot syndrome (MEWDS) is a rare fundus disease, characterized by acute vision loss and visual field defects. Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS. However, as the number of reported cases increases, secondary MEWDS occurs in other related retinal diseases and injuries, exhibiting some special characteristics. The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy (MFC/PIC), acute zonal occult outer retinopathy, best vitelliform macular dystrophy, pseudoxanthoma elasticum, and ocular toxoplasmosis. The related retinal injury is laser photocoagulation, surgery, and trauma. Although primary MEWDS often have a self-limiting course, secondary MEWDS may require treatment in some cases, according to the severity of concomitant diseases and complications. Notably, MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation, needs positive treatment with corticosteroids. The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch's membrane. The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances. Its prognosis and treatment depend on the severity of complications. Current studies propose that the etiology is associated with immune factors, including viral infection, inflammation in choroid and Bruch's membrane, and antigen exposure caused by retinal and/or choroidal insults. More pathogenic studies should be conducted in the future. Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.

Current understanding of acute zonal occult outer retinopathy (AZOOR).

Acute Zonal Occult Outer Retinopathy (AZOOR) is characterized by sudden visual impairment, often presenting with scotoma and photopsia in young to middle-aged adults, showing a female predominance. This condition, distinct from genetic disorders like retinitis pigmentosa, lacks a hereditary basis and exhibits unique fundus changes and imaging features indicative of outer retinal dysfunction. Recent advancements have broadened our understanding, identifying variants like Acute Annular Outer Retinopathy (AAOR) and Multizonal outer retinopathy and retinal pigment epitheliopathy (MORR), each with specific clinical presentations and imaging characteristics. The diagnosis of AZOOR and its variants primarily relies on excluding other conditions through comprehensive evaluation, including imaging and serological testing. Treatment approaches, including the use of corticosteroids and immunosuppressives, remain debated, with some evidence suggesting benefits in theearly stages. The prognosis of AZOOR varies, with most patients experiencing stabilization, although complications like choroidal neovascularization may occur, requiring targeted therapy. This manuscript elucidates the complexity of AZOOR, emphasizing the necessity of high clinical suspicion and the role of advanced imaging in diagnosis and management.

Incidence and Clinical Characteristics of COVID-19 Ophthalmopathy Following the Termination of Dynamic Zero COVID-19 Strategy in China

ABSTRACT Ocular involvement is not uncommon in patients with COVID-19. However, the incidence of COVID-19 ophthalmopathy in COVID-19 patients is still not clear. In this prospective case series study, we recruited 2445 consecutive cases presenting at Neuro-ophthalmology clinic of our Eye Center during the last resurgence of SARS-CoV-2 infection from 8 December 2022 to 15 March 2023 in China, 149 cases were diagnosed as COVID-19 ophthalmopathy, 87 cases were female, with a mean age of 43.2 years, and the mean follow-up time was 15.4 weeks. One hundred and twenty of 149 cases suffered from systemic symptoms mostly manifesting as fever, cough and muscle pain prior to or soon after ocular involvement. The most common COVID-19 ophthalmopathy was optic neuritis (51/149), followed by acute zonal occult outer retinopathy complex disease (31/149), uveitis (17/149), ocular mobility disorder-related (third, fourth, or sixth) cranial nerve neuritis (15/149), anterior ischaemic optic neuropathy (9/149), retinal artery occlusion (8/149), retinal microangiopathy including retinal haemorrhage and cotton wool spot (8/149), viral conjunctivitis (7/149), retinal vein occlusion (3/149), viral keratitis (2/149), ptosis (2/149), and other rare ocular diseases. Except 5 cases with central retinal artery occlusion, other 144 COVID-19 ophthalmopathy cases showed good response to steroid therapy. Our study revealed an incidence of 6.09% for COVID-19 ophthalmopathy in outpatients at our Neuro-ophthalmology clinic during last resurgence of COVID-19 in China, and demonstrated that SARS-CoV-2 infection could induce an initial onset or a relapse of ophthalmic diseases, and that ocular involvement might manifest as the initial or even the only presentation of COVID-19.

Acute zonal occult outer retinopathy as a luetic ocular manifestation

Aims/Purpose: Based on a clinical case seen in our setting, the purpose of this communication is to describe a case of ocular syphilis with an uncommon initial manifestation as well as its clinical and imaging features, diagnosis, treatment and evolution.Methods: We selected a case seen at the University Hospital Infanta Sofía in 2023. A 54‐year‐old male with Acquired Inmune Deficiency Syndrome (AIDS) under antiretroviral (ARV) treatment, diagnosed with cataract, who 1 month after surgery presented a paradoxical worsening of baseline visual acuity (VA) bilaterally accompanied by nyctalopia.Results: During the exam, we found VA from right eye (RE) of 0.03 and from left eye (LE) of 0.03. Fundus examination showed a bilateral central vitreous organization. Macular OCT from both eyes showed preserved foveal profile with pachychoroid associated with patchy absence of external limiting membrane, evident focal loss of ellipsoid zone and cysts in outer layers of the RE. Campimetry with practically abolished fields, neuroimaging study, complete serology including antirecoverin antibodies, and vitreous sample for microbiology were performed. From this study, it was found that the patient had a positive luetic seroconversion within a maximum period of five years. With these data, we oriented the differential diagnosis of the described retinopathy towards an infectious or toxic aetiology due to ARV drugs as the most probable causes. The patient was treated with intravenous penicillin with great improvement of vision and nyctalopia.Conclusions: Ocular syphilis is the great simulator par excellence and although infrequent, it can debut with atypical forms of uveitis.

Changes in Optical Coherence Tomography and Fundus Autofluorescence Findings in Acute Zonal Occult Outer Retinopathy

We report a case of peripapillary acute zonal occult outer retinopathy (AZOOR) in a 43-year-old woman. Fundus photographs showed no specific abnormal findings, while blue-light fundus autofluorescence (FAF) imaging revealed well-defined hyperfluorescent areas in the peripapillary region, excluding the macula. The ellipsoid zone (EZ) was absent on optical coherence tomography (OCT) images of this area. Visual field testing with Goldmann perimetry showed blind spot enlargement and multifocal electroretinogram showed corresponding amplitude reductions. Three months after the initial visit, the EZ had reappeared and both FAF and visual field had improved. FAF together with OCT may be useful in the evaluation and monitoring of AZOOR.

Latest advances in white spot syndromes: New findings and interpretations.

White spot syndromes (WSS) pose challenges in the field of ophthalmology, particularly in terms of accurate diagnosis and effective management. However, recent advancements in multimodal imaging (MMI) have significantly contributed to our understanding of WSS, allowing for improved characterization of these inflammatory chorioretinopathies. By employing various imaging modalities, including fundus fluorescein angiography, indocyanine green angiography, fundus autofluorescence, optical coherence tomography (OCT), ultra-widefield imaging, and OCT angiography, researchers and clinicians have gained valuable insights into the underlying pathophysiological changes and clinical progression of WSS. Furthermore, MMI has unveiled novel and atypical variants within the spectrum of WSS, expanding our knowledge in this field. Notably, the identification of secondary forms of WSS occurring concurrently with unrelated chorioretinal disorders has suggested a potential autoimmune mechanism underlying these conditions. The introduction of MMI has also facilitated a more comprehensive evaluation of previously ill-defined entities, such as acute zonal occult outer retinopathy, leading to improved diagnostic criteria and enhanced recognition of distinct features. This review paper provides a comprehensive overview of the latest advances and interpretations in WSS. By integrating MMI into the diagnosis and management of these conditions, this review aims to enhance patient outcomes and provide valuable insights into the complexities surrounding WSS.

MULTIZONAL OUTER RETINOPATHY AND RETINAL PIGMENT EPITHELIOPATHY (MORR): A Newly Recognized Entity or an Unusual Variant of AZOOR?

To describe specific clinical, multimodal imaging, and natural history features of an unusual variant of acute zonal occult outer retinopathy. Retrospective, observational, longitudinal, multicenter case series. Patients exhibiting this unusual clinical condition among cases previously diagnosed with acute zonal occult outer retinopathy were included. Multimodal imaging, laboratory evaluations, and genetic testing for inherited retinal diseases were reviewed. Twenty eyes from 10 patients (8 females and 2 males) with a mean age of 54.1 ± 13.3 years (range, 38-71 years) were included. The mean follow-up duration was 13.1 ± 5.3 years (range, 8-23 years). Presenting symptoms were bilateral in 7 patients (85% of eyes) and included scotomata and photopsia. All patients had bilateral lesions at presentation involving the peripapillary and far peripheral retina. Baseline optical coherence tomography showed alteration of the retinal pigment epithelium and photoreceptor layers corresponding to zonal areas of fundus autofluorescence abnormalities. Centrifugal and centripetal progression of the peripapillary and far-peripheral lesions, respectively, occurred over the follow-up, resulting in areas of complete outer retinal and retinal pigment epithelium atrophy. Initial alteration of photoreceptors and retinal pigment epithelium and a stereotypical natural course that includes involvement of the far retinal periphery, characterize this unusual condition. It may represent a variant of acute zonal occult outer retinopathy or may be a new entity. We suggest to call it multizonal outer retinopathy and retinal pigment epitheliopathy .

Acute Idiopathic Blind Spot Enlargement Syndrome (AIBSES) in the Era of OCT - a Review.

There are only about 100 case reports on the Acute Idiopathic Blind Spot Enlargement Syndrome (AIBSES). This is characterised by the eponymous visual field loss in the blind spot area, acute onset photopsia, and funduscopically little or no change in the optic disc area, with conspicuous outer retinal bands on optical coherence tomography (OCT). Typical is the unilateral occurrence. Predominantly young women are affected. While previous reviews of AIBSES either predate the introduction of OCT or focus on differentiation from potentially related outer retinal conditions (e.g., multiple evanescent white dot syndrome and acute zonal occult outer retinopathy), the present review will concentrate on the current perspective and treatment strategies that have been developed and will aim to help increase awareness. Since the first description of AIBSES in the late 1980s, the introduction of OCT has simplified the diagnosis and characterisation of AIBSES as a disease of the outer retina. Nevertheless, misdiagnosis remains common in the spectrum of optic neuritis, as AIBSES may be ignored in differential diagnosis.

Primary versus Secondary Elevations in Fundus Autofluorescence.

The method of quantitative fundus autofluorescence (qAF) can be used to assess the levels of bisretinoids in retinal pigment epithelium (RPE) cells so as to aid the interpretation and management of a variety of retinal conditions. In this review, we focused on seven retinal diseases to highlight the possible pathways to increased fundus autofluorescence. ABCA4- and RDH12-associated diseases benefit from known mechanisms whereby gene malfunctioning leads to elevated bisretinoid levels in RPE cells. On the other hand, peripherin2/RDS-associated disease (PRPH2/RDS), retinitis pigmentosa (RP), central serous chorioretinopathy (CSC), acute zonal occult outer retinopathy (AZOOR), and ceramide kinase like (CERKL)-associated retinal degeneration all express abnormally high fundus autofluorescence levels without a demonstrated pathophysiological pathway for bisretinoid elevation. We suggest that, while a known link from gene mutation to increased production of bisretinoids (as in ABCA4- and RDH12-associated diseases) causes primary elevation in fundus autofluorescence, a secondary autofluorescence elevation also exists, where an impairment and degeneration of photoreceptor cells by various causes leads to an increase in bisretinoid levels in RPE cells.

Blue-Light Fundus Autofluorescence (BAF), an Essential Modality for the Evaluation of Inflammatory Diseases of the Photoreceptors: An Imaging Narrative.

Our purpose is to describe blue-light fundus autofluorescence (BAF) features of inflammatory diseases of the outer retina characterised by photoreceptor damage. BAF from patients diagnosed with secondary and primary inflammatory photoreceptor damage were retrospectively analyzed and compared to other imaging modalities including fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral domain optical coherence tomography (SD-OCT). Multiple evanescent white dot syndrome (MEWDS), idiopathic multifocal choroiditis (MFC), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous choroiditis (SC), and acute syphilitic posterior placoid chorioretinitis (ASPPC), all cases corresponding to secondary photoreceptor diseases caused by inflammatory choriocapillaris nonperfusion, were included and compared to primary photoreceptor disease entities, including acute zonal occult outer retinopathy (AZOOR) and cancer-associated retinopathy (CAR). Both groups showed increased BAFs of variable intensity. In severe cases of APMPPE and ASPPC, BAF also showed hypoautofluorescent areas. In group 1 (secondary diseases) BAF hyperautofluorescent areas were associated with colocalized ICGA hypofluorescent areas, indicating choriocapillaris nonperfusion; whereas in group 2 (primary diseases), no ICGA signs were detected. The associated colocalized areas of hypofluorescence on ICGA in the first group, which were absent in the second group, were crucial to allow the differentiation between primary (photoreceptoritis) and secondary (choriocapillaritis) photoreceptor diseases. BAF patterns in inflammatory diseases of the outer retina can give relevant information on the photoreceptor and RPE involvement, with ICGA being crucial to detect concurring choriocapillaris damage and differentiating the two pathologies.

Acute zonal occult outer retinopathy misdiagnosed as giant cell arteritis: a challenging case

Background: Acute zonal occult outer retinopathy (AZOOR) is a rare autoimmune retinopathy that is challenging to diagnose and treat. It usually presents with subtle fundus changes and severe visual symptoms. Herein, we report a challenging case of AZOOR, emphasizing that multimodal imaging could be valuable in diagnosis and monitoring of treatment response.
 Case Presentation: A 53-year-old woman presented to the emergency department with a one-week history of subacute, severe, painless vision loss without photopsia in her right eye. Her best-corrected distance visual acuity was 20/800 in the right eye and 20/20 in the left eye. Slit-lamp examination findings were unremarkable, and intraocular pressure was normal in both eyes. Initially, fundus examination findings appeared normal; however, serum levels of inflammatory markers were elevated. Brain and orbital magnetic resonance imaging results were unremarkable. A relative afferent pupillary defect was present in subsequent follow-up examinations at the hospital. The patient initially received a diagnosis of posterior ischemic optic neuropathy secondary to occult giant cell arteritis, underwent steroid treatment, and was evaluated by rheumatology and neurology consultants. Both consultants concurred with the presumed diagnosis. Subsequent multimodal imaging in the ophthalmology clinic revealed a trizonal pattern of fundus autofluorescence. Corresponding to these areas, we noted a loss of the ellipsoid zone on optical coherence tomography, depression on multifocal electroretinogram, and scotoma on visual field testing. Accordingly, the diagnosis of AZOOR was made. The patient was referred back to the rheumatologist for initiation of steroid-sparing treatment, and methotrexate was administered. Five months after the initial presentation, the patient showed significant visual field improvement in both eyes.
 Conclusions: Eye care practitioners should consider AZOOR in the differential diagnosis of patients with subacute painless severe unilateral vision loss and unremarkable findings on fundus examination. Multimodal imaging could be valuable in diagnosis and monitoring of treatment response, as observed in the current case. Further studies with larger sample sizes are needed to confirm the value of multimodal imaging and the available management options for AZOOR.

A case of syphilitic outer retinopathy like acute zonal occult outer retinopathy

A case of syphilitic outer retinopathy like acute zonal occult outer retinopathy

Acute annular outer retinopathy (AAOR)—First report from India

Acute annular outer retinopathy (AAOR) is a very rare variant of white dot syndrome. Ocular imaging helps in distinguishing it from acute zonal occult outer retinopathy. We report the first case of AAOR, from India, with multimodal imaging, highlighting the role of early immunomodulatory therapy in visual prognosis.

Acute zonal occult outer retinopathy – An acquired bilaterally symmetrical fovea-sparing lesion

Acute zonal occult outer retinopathy – An acquired bilaterally symmetrical fovea-sparing lesion

A systematic review of acute zonal occult outer retinopathy with a focus on attempted treatment modalities.

A systematic review of acute zonal occult outer retinopathy with a focus on attempted treatment modalities.

Bilateral recurrent choroidal neovascularization in AZOOR

AbstractWe present a case of acute zonal occult outer retinopathy (AZOOR) in a 61‐year‐old man who presented associated recurrent choroidal neovascularization as a complication in both eyes; he was managed with several intravitreal anti vascular endothelial growth factor (anti‐VEGF) injections in both eyes as well as with Prednisone and Methotrexate, which in improved the disease control.

A multicenter study of ocular inflammation after COVID-19 vaccination.

To report the characteristics of a case series of ocular inflammatory events following COVID-19 vaccination in Japan. Retrospective multicenter study METHODS: In this retrospective multicenter survey, a questionnaire was sent to 16 Japanese hospitals that had uveitis specialty clinics. Information on patients who developed ocular inflammatory events within 14 days of COVID-19 vaccination between February 2021 and December 2021 was collected. Thirty-seven patients were diagnosed with ocular inflammatory events following COVID-19 vaccination. The mean age was 53.4 ± 16.4 years (range, 26-86 years), and the mean time to onset after vaccination was 6.3 ± 4.2 days (range, 1-14 days). Vogt-Koyanagi-Harada disease (VKH) was the most common event (n = 17 patients, 46%), followed by anterior uveitis (n = 6), infectious uveitis (n = 3), acute zonal occult outer retinopathy (AZOOR) (n = 2), sarcoidosis-associated uveitis (n = 1), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1), optic neuritis (n = 1), multiple evanescent white dot syndrome (MEWDS) (n = 1), Posner-Schlossman syndrome (n = 1), and unclassified uveitis (n = 4). Twenty-eight cases occurred after BNT162b2 vaccination (Pfizer-BioNTech) and 8 after mRNA-1273 vaccination (Moderna), whilst 1 patient had no information about vaccine type. COVID-19 vaccination can be related to various types of ocular inflammatory events. When we encounter patients with ocular inflammatory disease, we should consider that it may be an adverse effect of COVID-19 vaccination.