Use of Ultra-Widefield Fluorescein Angiography to Guide the Treatment to Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis-Case Report and Literature Review.

PURPOSE: To review the clinical features, diagnosis, and treatment of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) and to report a case with the use of ultra-widefield fluorescein angiography (UWFA) for confirming the precise staging of IRVAN and aid in early treatment. The patient improved after being treated with intravitreal aflibercept injection. RESULTS: A 26-year-old female complained of progressive blurred vision OD for one week. Her BCVA was 0.6 OD and 1.0 OS. Fundus examination showed vitritis, retinal hemorrhage, and vasculitis over bilateral eyes. Fluorescein angiography (FA) with a 55 degree of view revealed aneurysmal dilations of the peripapillary arteriole, peripapillary focal leakage, venous leakage, and capillary nonperfusion area. Stage 2 IRVAN was impressed OU. Oral prednisolone was administered. After four months, she experienced decreased visual acuity OS. Optical coherence tomography (OCT) revealed subretinal and intraretinal fluid with hyperreflective material. One posterior subtenon triamcinolone and one intravitreal aflibercept injection were performed OS, and macular edema subsided. A 105-degree ultra-widefield fluorescein angiography (UWFA) showed multiple peripheral background hypofluorescence areas corresponding to capillary nonperfusion. Retinal neovascularization (NV) was found OS, which had not been revealed by the previous 55-degree FA. Stage 3 IRVAN was made OS and panretinal laser photocoagulation (PRP) was performed. Oral prednisone and cyclosporine were prescribed. Her vision improved to 1.0 OU. CONCLUSION: UWFA provides visualization of peripheral retinal pathology and for precise staging. It also had direct implications in the follow-up and treatment strategy.

Retinal microvasculature features in patients with Behcet's disease: a systematic review and meta-analysis.

This meta-analysis aimed to analyze retinal microvasculature features in eyes with Behçet's disease (BD) using optical coherence tomography angiography (OCTA). Electronic databases, including PubMed, Web of Science, Embase, and Cochrane Library, were comprehensively searched for published studies comparing retinal microvasculature characteristics between eyes with BD and controls. Continuous variables were calculated using the mean difference (MD) with 95% confidence interval (CI). Review Manager software (version 5.30) was used to conduct statistical analysis. A total of 13 eligible studies involving 599 eyes with BD and 622 control eyes were included in the meta-analysis. The pooled results showed that the macular whole enface superficial and deep vessel density (VD) values measured by OCTA were significantly lower in eyes with BD than in control eyes (superficial VD: MD = - 3.05, P < 0.00001; deep VD: MD = - 4.05, P = 0.0004). The foveal superficial and deep VD values were also significantly lower in the BD group than in the control group (superficial VD: MD = - 1.50, P = 0.009; deep VD: MD = - 4.25, - = 0.03). Similarly, the analysis revealed a significant reduction in the parafoveal superficial and deep VD in eyes with BD than in control eyes (superficial VD: MD = - 3.68, P < 0.00001; deep VD: MD = - 4.95, P = 0.0007). In addition, the superficial and deep foveal avascular zones (FAZs) were significantly larger in patients with BD than in controls (superficial FAZ: MD = 0.06, P = 0.02; deep FAZ: MD = 0.12, P = 0.03). The present meta-analysis found that macular whole enface VD, foveal VD, and parafoveal VD were lower in eyes with BD, and the FAZ was larger in patients with BD. The findings suggest that OCTA can assist clinicians in diagnosing and monitoring the status of patients with BD.

Peripapillary optical coherence tomography as an alternative to fluorescein angiography for monitoring Behcet's retinal vasculitis.

To study the correlation of OCT parameters including central subfield macular thickness (CSMT), peripapillary retinal thickness (PRT), and peripapillary retinal nerve fiber layer thickness (PNFLT) with fluorescein angiography (FA) in evaluation of inflammatory activity in Behcet's retinal vasculitis. In this case-series, concurrent FA and OCT were performed. A scoring system was devised for FA. PNFLT in 3.4-mm-diameter circle as well as PRT in doughnut shaped regions between the 1-mm- and 2.2-mm-diameter and between the 2.2-mm- and 3.45-mm-diameter circles was measured. The correlation of FA and OCT parameters was analyzed. A total of 105 sets of FA from 28 eyes (15 patients) were reviewed. Four (26.6%) were female and mean age was 31.6 ± 8.49 years. Each micron increase in CSMT, PRT2.2, PRT3.45, and PNFLT, caused a rise of 0.018 (95% CI 0.008-0.027, P < 0.001, r = 0.413), 0.053 (95% CI 0.035-0.070, P < 0.001, r = 0.443), 0.086 (95% CI 0.065-0.108, P < 0.001, r = 0.707), and 0.185 (95% CI 0.152-to 0.218, P < 0.001, r = 0.850) unit in FA score, respectively. Parameters having significant correlation with angiographic inflammatory activity, were CSMT, PRT2.2, PRT3.45 and RNFLT. Those with the strongest correlation, PRT3.45 and PNFLT, may be considered as quantitative non-invasive alternatives to FA for monitoring Behcet's retinal vasculitis.

Parafoveal Microvascular Alterations in Ocular and Non-Ocular BehÒ«et's Disease Evaluated With Optical Coherence Tomography Angiography.

Purpose: To compare quantitative optical coherence tomography angiography (OCT-A) measurements of the parafoveal microvasculature in retinal capillary plexuses among BehÒ«et uveitis (BU) patients, non-ocular BehÒ«et's disease (NOBD) patients, and healthy volunteers (HVs). Methods: Sixty-eight subjects were enrolled in this prospective observational cross-sectional study. OCT-A imaging was performed using the Heidelberg Engineering Spectralis OCT. A custom algorithm was developed to calculate the vessel density (VD) in three retinal vascular layers: deep capillary plexus, intermediate capillary plexus, and superficial vascular plexus. The foveal avascular zone (FAZ) and acircularity index were calculated for the whole retinal vascular complex. Results: We analyzed one eye from 21 BU patients (age, 51 ± 10 years), 23 NOBD patients (age, 48 ± 14 years), and 22 HVs (age, 44 ± 13 years). One-way multivariate analysis of covariance showed a statistically significant difference in VD among the three groups when combining the layers after controlling for scan quality (P < 0.001). The VD was lowest in the BU group and highest in the HV group in all layers. The FAZ area was also statistically significant different among the groups (P < 0.005), with the largest FAZ areas in BU patients and smallest FAZ areas in the HV group. However, no statistically significant difference was found for the acircularity index. Conclusions: The parafoveal microvasculature is affected not only in BU patients but also in NOBD patients. Most deviations in the retinal microcirculation in BehÒ«et patients were found in the deeper layers of the retina by using the quantitative VD measurement.

Cerebrovascular reactivity in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations.

Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S) is a small vessel disease caused by TREX1 mutations. RVCL-S is characterized by retinal vasculopathy and brain white matter lesions with and without contrast enhancement. We aimed to investigate cerebrovascular reactivity (CVR) in RVCL-S. In this cross-sectional observational study, 21 RVCL-S patients, 23 mutation-negative family members, and 31 healthy unrelated controls were included. CVR to a hypercapnic challenge was measured using dual-echo arterial spin labeling magnetic resonance imaging. Stratified analyses based on age were performed. We found that CVR was decreased in gray and white matter of RVCL-S patients compared with family members and healthy controls (ANCOVA; P < 0.05 for all comparisons). This was most noticeable in RVCL-S patients aged ≥40 years (ANCOVA, P < 0.05 for all comparisons). In RVCL-S patients aged < 40 years, only CVR in white matter was lower when compared to healthy controls (P < 0.05). Gray matter CVR was associated with white matter lesion volume in RVCL-S patients (r = -0.527, P = 0.01). In conclusion, impaired cerebrovascular reactivity may play an important role in the pathophysiology of RVCL-S and may be an useful early biomarker of cerebrovascular disease severity.

Multimodal Imaging Characteristics and Functional Test Findings in a Case of Acute Macular Neuroretinopathy Accompanied by Behçet Disease.

Purpose: To report a case of acute macular neuroretinopathy (AMN) in Behçet Disease.Case: A 23-year-old male presented with a complaint for central scotoma in his right eye. He had been diagnosed with Behçet Disease 3 years ago. Best-corrected visual acuity (BCVA) was 20/20. Anterior chamber and fundus examinations were unremarkable. Optical coherence tomography revealed a paracentral area of outer nuclear layer thinning. Infrared reflectance showed a well-defined, circular, hyporeflective area. Optical coherence tomography angiography revealed an area of capillary dropout in deep retinal capillary plexus corresponding to that hyporeflective lesion. Microperimetry test showed decreased macular sensitivity on the lesion area and the loss of the macular integrity. In multifocal electroretinogram, diminished amplitudes of the central cone responses were detected nasal to fixation.Conclusion: Behçet disease is a cause of occlusive retinal vasculitis. Accompanied retinal microvascular disease may be a possible risk factor of AMN suggesting ischemic etiopathogenesis for AMN.

EVALUATION OF SEGMENTAL RETINAL ARTERITIS WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe the vascular anatomy and intraluminal flow characteristics of segmental retinal arteritis (SRA) using structural and angiographic optical coherence tomography (OCT). METHODS: Retrospective case series of consecutive patients presenting with SRA. All patients were evaluated at presentation with fundus photography, spectral domain OCT, and OCT angiography. One patient was imaged with dense B-scan OCT angiography. RESULTS: Three eyes of three male patients were evaluated. All examinations were consistent with reactivation of ocular toxoplasmosis with an area of active retinochoroiditis adjacent to a focal chorioretinal scar. Spectral domain OCT through areas of SRA noted on clinical examination demonstrated areas of hyperreflectivity circumscribing the affected vessel with a normoreflective lumen. Optical coherence tomography angiography and dense B-scan OCT angiography demonstrated narrowing of the intraluminal flow signal that correlated with areas of segmental hyperreflectivity on spectral domain OCT. Vascular sections proximal and distal to areas of SRA showed normal flow signal. CONCLUSION: Vessels with SRA demonstrated hyperreflectivity highlighting the vessel wall on spectral domain OCT. Optical coherence tomography angiography showed narrowing of the flow signal within these segments suggesting reduced lumen diameter. Coupling these finding with previous indocyanine green imaging findings in SRA, the collective data suggest the plaques are localized within the vessel wall to either the endothelium or the muscular tunica media without occlusion of the vessel lumen.

SLE presenting as DAH and relapsing as refractory retinitis.

Dear Editor, A 17-year-old boy, diagnosed with Systemic Lupus Erythematosus (SLE), presented to ophthalmology department with gradual painless diminution of vision in both eyes (right more than left). He had already received 6 pulses of cyclophosphamide and steroids at monthly intervals one year back for diffuse alveolar hemorrhage (DAH) and was on maintenance oral 40 mg prednisolone and 3 grams mycophenolate mofetil (MMF). There was no history of oliguria, skin rash, joint pain, oral ulcers, photosensitivity or any neurological deficit in this presentation. There was no proteinuria, hematuria or worsening of renal function.

High-Resolution Imaging of Retinal Vasculitis by Flood Illumination Adaptive Optics Ophthalmoscopy: A Follow-up Study.

Purpose: To monitor perivascular sheathing during the course of retinal vasculitis by flood illumination adaptive optics ophthalmoscopy (AOO). Methods: Perivenous sheathing and venous diameters were quantitatively analyzed by semi-automatic segmentation of AOO images in 12 eyes of treatment-naive patients with retinal vasculitis. Results: The width of venous sheathing ranged from 45 to 225 µm (mean 101.0 µm ± 54.3). In 10 cases, the underlying vein showed focal narrowing (mean ± SD 14% ± 10). Focal narrowing of arteries was also present in one eye. At presentation, width of sheathing and vessel diameters were not correlated with fluorescein leakage. During follow-up, 5 eyes showed an increase in vein diameter or resolution of narrowing and in 10 eyes a thinning of vascular sheathing was observed (p= .003). Conclusions: Perivenous sheathing may be quantitatively analyzed and monitored by AOO. AOO may therefore contribute to monitor vascular sheathing during posterior uveitis.

Retinal Vasculitis Associated with Ipilimumab.

PURPOSE: To describe a case of retinal vasculitis associated with ipilimumab. METHODS: Case report. RESULTS: A 49-year-old Caucasian man presented with anterior uveitis of the left eye. He had a history of chronic myeloid leukemia undergoing ipilimumab therapy. He was treated with topical corticosteroids and achieved inactive inflammation. Ipilimumab was stopped by his oncologist since he manifested other immune-related adverse events (irAEs). Five months later, his visual acuity decreased in his left eye and optical coherence tomography demonstrated new cystoid macular edema. Fluorescein angiography revealed diffuse capillary leakage of the left eye. He received oral prednisone with improvement of both macular edema and vascular leakage, however, both remained persistent. He received an intravitreal injection of a 0.7 mg dexamethasone implant in the left eye with subsequent resolution of macular edema and vasculitis. CONCLUSIONS: The occurrence of retinal vasculitis with ipilimumab expands the spectrum of ocular irAEs related to immune checkpoint inhibitors.

Wide-field angiography for diagnosis and follow-up of Eales disease: a case series / Angiografia de amplo campo para diagnóstico e monitoramento da doença de Eales: série de casos

ABSTRACT Wide-field angiography enables assessing peripheral areas with better quality and gives greater deep focus, which improves the image periphery. Some studies have proposed the usefulness of these angiographic systems in inflammatory diseases of the retina. However, few studies have evaluated this technique in Eales disease. We present a case series in which 5 eyes of 3 patients with Eales disease were evaluated by using retinal fluorescein angiography with 30º, 50º, and 150º lenses in a laser-scanning ophthalmoscope. These cases highlight the usefulness of wide-field fluorescein angiography in the diagnosis and follow-up of peripheral ischemic retinal areas in Eales disease, which enables better follow-up than possible with conventional fluorescein angiography images.

RESUMO A angiografia de campo amplo permite avaliar áreas periféricas com melhor qualidade e proporciona maior foco profundo, melhorando a imagem da periferia. Alguns estudos têm proposto a utilidade desses sistemas angiográficos nas doenças inflamatórias da retina. No entanto, poucos estudos avaliaram esta técnica na doença de Eales. Apresentamos uma série de casos em que 5 olhos de 3 pacientes com doença de Eales foram avaliados usando angiografia de fluoresceína da retina com lentes de 30º, 50º e 150º em um oftalmoscópio de varredura a laser. Esses casos destacam a utilidade da angiografia com fluoresceína de campo amplo no diagnóstico e no acompanhamento das áreas isquêmicas periféricas da retina na doença de Eales, permitindo um melhor acompanhamento do o possível com imagens por angiofluoresceinografia convencional.

Wide-field angiography for diagnosis and follow-up of Eales disease: a case series.

Wide-field angiography enables assessing peripheral areas with better quality and gives greater deep focus, which improves the image periphery. Some studies have proposed the usefulness of these angiographic systems in inflammatory diseases of the retina. However, few studies have evaluated this technique in Eales disease. We present a case series in which 5 eyes of 3 patients with Eales disease were evaluated by using retinal fluorescein angiography with 30º, 50º, and 150º lenses in a laser-scanning ophthalmoscope. These cases highlight the usefulness of wide-field fluorescein angiography in the diagnosis and follow-up of peripheral ischemic retinal areas in Eales disease, which enables better follow-up than possible with conventional fluorescein angiography images.

Vasculitis retiniana y del disco óptico en el síndrome de Susac / Retinal and optic disc vasculitis in Susac's syndrome

Mujer de 42 años, sin antecedentes de interés que acude con cefalea severa, náuseas, vómitos, pérdida de la audición y alteraciones mentales con desorientación y confusión. El examen oftalmológico reveló la presencia de hiperemia del disco óptico derecho y de áreas focales de oclusión arteriolar en ambos ojos. La audiometría puso de manifiesto una hipoacusia bilateral neurosensorial. En la resonancia magnética cerebral se detectaron múltiples lesiones de pequeño tamaño hiperintensas localizadas en el esplenio, cuerpo calloso, ganglios basales y sustancia blanca

The case is presented of 42 year-old woman with no significant medical history, with severe headaches, nausea and vomiting, hearing loss, and alteration of mental status with disorientation and confusion. Ophthalmic examination showed optic disc hyperaemia in right eye, and focal areas of arteriolar occlusion in both eyes. Audiometry demonstrated bilateral neurosensory hypoacusis. Magnetic Resonance Imaging showed multiple small round hyperintense lesions located in the splenium, corpus callosum, basal ganglia, and white matter

Spectral domain optical coherence tomography evaluation of macular changes in Eales disease.

PURPOSE: The purpose of the study was to describe macular changes in treatment-naïve eyes with Eales disease using spectral domain optical coherence tomography (SD-OCT). METHODS: A cross-sectional study was done on 79 eyes of 66 patients with Eales disease. Best-corrected visual acuity (BCVA), slit-lamp biomicroscopy (SLB), indirect ophthalmoscopy, fundus fluorescein angiography (FFA), and quantitative (central macular thickness [CMT]) and qualitative analysis on SD-OCT were performed. RESULTS: Forty-six (58.2%) eyes had macular involvement as assessed with SD-OCT, while in 33 (41.8%) eyes, macula was not affected. Macular edema was the most common feature when macula was affected followed by epiretinal membrane. Mean CMT was higher (315.3 ± 102.3 µm) in eyes with macular involvement than those without it (243.8 ± 19.3 µm). Eyes with active vasculitis involving larger vessels and neovascularization had greater chance of macular involvement. SLB and FFA alone missed 28.3% and 50% eyes with macular abnormalities on SD-OCT, respectively. CONCLUSION: While the clinical description of Eales disease points mainly to a peripheral location, macular involvement can be commonly picked up when SD-OCT is used. Macular involvement when present is associated with a poorer BCVA.

Multimodal imaging questions etiology of idiopathic retinal vasculitis, aneurysms and neuroretinitis syndrome (IRVAN syndrome).

Idiopathic retinal vasculitis, aneurysms and neuroretinitis (IRVAN) syndrome is a rare entity of unknown etiology for which many hypotheses have been proposed with inflammation being the most commonly accepted hypothesis. We report cases of a 9 year old girl and a 22 year old male patient with diagnosis of IRVAN syndrome. The conclusions drawn from the clinical examination and multimodal imaging including optical coherence tomography angiography of the patients are discussed. Our conclusions and interpretation point towards IRVAN being a developmental vascular anomaly rather than a consequence of inflammation. It is thus proposed to be renamed as Idiopathic retinal arteriolar aneurysm syndrome (IRAA).

Non-invasive method of monitoring retinal vasculitis in patients with birdshot chorioretinopathy using optical coherence tomography.

BACKGROUND/AIMS: To investigate the utility of using montaged optical coherence tomography (OCT) thickness maps to monitor perivascular thickness as a marker of vasculitic activity in patients with large-vessel retinal vasculitis. METHODS: This is a retrospective cohort study of 22 eyes of 11 patients with a history of retinal vasculitis associated with birdshot chorioretinopathy (BCR). Patients had serial spectral domain 6×6 mm cube OCT scans centred on the fovea, optic nerve and proximal branches of the superior and inferior retinal vessels. OCT thickness change maps for each respective region were analysed. Changes in perivascular thickness were confirmed by assessing vasculitic activity on fluorescein angiography (FA), when clinically indicated. RESULTS: In three patients, montaged OCT scans were acquired at diagnosis and serially through initial treatment. In all three patients, montaged OCT demonstrated reduced perivascular thickening with oral prednisone treatment, which was confirmed by FA showing reduced vascular leakage in both eyes. Eight patients had serial montaged OCT scans after diagnosis and initial treatment of BCR. Four of these patients showed fluctuations in perivascular thickness during flares and treatment that were confirmed by either increased or decreased vascular leakage on FA. The other four patients remained quiet on their immunosuppressive treatment regimens, and no changes in perivascular thickness were detected. CONCLUSIONS: Evaluating large-vessel perivascular thickness on OCT scans may be a useful method for non-invasively monitoring posterior pole large-vessel retinal vasculitis.