Characteristics and risk factors of retinal vasculopathy in antiphospholipid syndrome.

BACKGROUND: Retinal vasculopathy including retinal artery occlusion (RAO) or retinal vein occlusion (RVO) was recently found to occur more frequently in antiphospholipid syndrome (APS) patients than non-APS patients. This study aims to investigate the clinical manifestation and risk factors of retinal vasculopathy among APS patients. METHODS: In this single-center prospective cohort study, we evaluated APS patients with or without retinal vasculopathy during 2018-2020 at Peking Union Medical College Hospital. Clinical variables were compared, and a logistical regression model was built to explore risk factors. Hierarchical cluster analysis using Euclidean distances was applied to identify clusters of variables. RESULTS: A total of 310 APS patients (67.4% female, mean age 38.1 years) were included, of whom 18 (5.8%) were diagnosed with retinal vasculopathy (9 with RVO and 9 with RAO). No significant differences were found among most demographic characteristics, clinical manifestations, or antibody profiles. APS-related heart valve disease (odds ratio OR 13.66, 95% confidence interval CI 4.55-40.98), APS nephropathy (OR 12.77, 95% CI 4.04-40.35), and thrombocytopenia (OR 2.63, 95% CI 1.01-6.89) were predictive of retinal vasculopathy. APS-related heart valve disease and nephropathy were also found to be statistically significant predictors in multivariate logistical regression analysis. Non-criteria manifestations were aggregated with retinal vasculopathy from a cluster analysis of variables. CONCLUSION: Patients with APS-related heart valve disease and nephropathy suffered a higher risk of retinal vasculopathy. The underlying mechanisms of aPL-associated retinal vasculopathy may involve thrombotic microangiopathy, leading to poor prognosis and therapeutic changes.

Serial magnetic resonance imaging changes of pseudotumor lesions in retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a case report.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an adult-onset rare monogenic microvasculopathy. Its typical neuroimaging features are punctate white matter lesions or pseudotumor alterations. RVCL-S is often under-recognized and misdiagnosed because of its rarity and similar imaging manifestations to multiple sclerosis or brain malignant mass. CASE PRESENTATION: Here we report a case of a 36-year-old Chinese man who developed multiple tumefactive brain lesions spanning over two years leading to motor aphasia, cognitive decline, and limb weakness. He also presented with slight vision loss, and fundus fluorescein angiography indicated retinal vasculopathy. He underwent brain biopsies twice and showed no evidence of malignancy. Given the family history that his father died of a brain mass of unclear etiology, RVCL-S was suspected, and genetic analysis confirmed the diagnosis with a heterozygous insertion mutation in the three-prime repair exonuclease 1 gene. He was given courses of corticosteroids and cyclophosphamide but received little response. CONCLUSIONS: The present case is one of the few published reports of RVCL-S with two-year detailed imaging data. Serial magnetic resonance images showed the progression pattern of the lesions. Our experience emphasizes that a better understanding of RVCL-S and considering it as a differential diagnosis in patients with tumefactive brain lesions may help avoid unnecessary invasive examinations and make an earlier diagnosis.

Multimodal imaging of bilateral ischemic retinal vasculopathy associated with Berger's IgA nephropathy: case report.

BACKGROUND: Berger's IgA nephropathy (IgAN) is the most common primary glomerulonephritis. However, some rare cases of retinal manifestations have been described, with only two cases of retinal vasculopathy reported in the literature. Here we report an uncommon case of bilateral ischemic retinal vasculopathy associated with Berger IgAN, evaluated with complete multimodal imaging including ultra-wide field (UWF) imaging and swept source optical coherence tomography angiography (SS-OCTA). CASE PRESENTATION: A 51-year-old woman with a history of Berger's IgA nephropathy complained of visual impairment in both eyes. Fundus examination showed bilateral peripapillary arterial attenuation and perivascular sheathing, associated to perifoveal telangiectatic lesions. There was a central scotoma in the perimetry of the right eye and peripheral visual field defect in the left eye. Full-field electroretinogram revealed significantly reduced oscillatory potentials. Spectral domain optical coherence tomography showed multiple focal areas of thinning of the inner retina, indicating long-lasting vascular occlusion lesions. UWF fluorescein angiography showed the presence of bilateral vasculitis, diffuse capillary leakage, macular ischemia and telangiectasia. SS-OCTA better highlighted the macular ischemia and vascular anomalies layer-by-layer. CONCLUSIONS: Retinal vasculopathy is a very rare condition observed in IgA nephropathy. To our knowledge, this is the first report of complete multimodal functional and structural imaging. UWF imaging was very useful for accurate and comprehensive disease assessment, and OCTA was able to assess posterior pole vascular lesions.

Occlusive retinal vasculopathy with macular branch retinal artery occlusion as a leading sign of atypical hemolytic uremic syndrome - a case report.

BACKGROUND: Hemolytic Uremic Syndrome (HUS) is a rare disorder characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure, considered within the group of thrombocytic microangiopathies. Ocular complications in HUS are very rare. Here, we report an adult patient who suffered from acute onset of paracentral scotoma, caused by branch retinal artery occlusion (BRAO), as a leading symptom of atypical HUS. CASE PRESENTATION: A 39-year-old healthy male was lately diagnosed with essential hypertension and mild renal impairment. He complained about acute onset of central scotoma in his left eye. Fundus examination revealed marked narrowing of retinal vessels, cotton wool spots and few retinal hemorrhages in both eyes. The patient was diagnosed with bilateral ischemic retinal vasculopathy and acute macular BRAO in his left eye. Workup revealed thrombocytopenia, worsening renal failure. Renal biopsy showed signs of chronic thrombotic microangiopathy. The patient was diagnosed with atypical HUS (aHUS) and started on plasmapheresis, together with eculizumab. As his condition continued to worsen, he was put on renal replacement therapy. Due to a persistent monoclone of IgG1, the patient underwent bone marrow biopsy which revealed Monoclonal Gammopathy of renal significance, triggering a HUS and treatment was initiated accordingly. Two months after initial presentation, the patient developed neovascularization of the optic disc (NVD) in his left eye, and was treated with 3 monthly intravitreal bevacizumab injections with complete regression of the NVD. The patient suffered from myocardial infarction in the later course and was lost for follow-up. He returned 11 months after the last bevacizumab injection because of sudden loss of vision in his left eye caused by a dense vitreous hemorrhage. Biomicroscopy revealed a new NVD in his right eye. The patient underwent panretinal photocoagulation in both eyes with regression of neovascularization. Vision improved and remained 20/20 in both eyes. CONCLUSION: We present a case report showing retinal ischemia can be linked with aHUS. As clinal diagnosis might be challenging, physicians should be aware of the rare ocular manifestations of this devastating multi-organ disease. In case of retinal ischemia, panretinal photocoagulation should be initiated soon to avoid blinding complications.

Retinal vasculopathy in children with systemic lupus erythematosus: report of two cases.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune, multisystem disease associated with a variable clinical course. SLE is more severe and is associated with higher mortality in children compared to adults. Eye involvement may be seen in up to a third of patients. Retinal vasculopathy is rare in children with SLE. We report two such cases. Both patients in this series had cotton-wool spots on fundus examination, and fundus fluorescein angiography revealed findings of occlusive micro-angiopathy. These findings are characteristic of lupus retinal vasculopathy. Fundus examination is crucial in diagnosing retinal vasculopathy. All children with SLE must be evaluated in detail to detect any retinal abnormalities and should be managed with aggressive immunosuppression to save their vision.

Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology.

BACKGROUND AND PURPOSE: Guidelines on monogenic cerebral small-vessel disease (cSVD) diagnosis and management are lacking. Endorsed by the Stroke and Neurogenetics Panels of the European Academy of Neurology, a group of experts has provided recommendations on selected monogenic cSVDs, i.e. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), autosomal dominant High Temperature Requirement A Serine Peptidase 1 (HTRA1), cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), Fabry disease, mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and type IV collagen (COL4)A1/2. METHODS: We followed the Delphi methodology to provide recommendations on several unanswered questions related to monogenic cSVD, including genetic testing, clinical and neuroradiological diagnosis, and management. RESULTS: We have proposed 'red-flag' features suggestive of a monogenic disease. General principles applying to the management of all cSVDs and specific recommendations for the individual forms of monogenic cSVD were agreed by consensus. CONCLUSIONS: The results provide a framework for clinicians involved in the diagnosis and management of monogenic cSVD. Further multicentre observational and treatment studies are still needed to increase the level of evidence supporting our recommendations.

Phenotypic Variability in a Mexican Mestizo Family with Retinal Vasculopathy with Cerebral Leukodystrophy and TREX1 Mutation p.V235Gfs*6.

BACKGROUND: Retinal vasculopathy with cerebral leukodystrophy (RVCL) is an adult-onset, autosomal dominant disease involving microvessels of the brain and eye resulting in central nervous system degeneration with visual disturbances, stroke, motor impairment, and cognitive decline. Frameshift mutations at the C-terminus of TREX1 gene are the molecular cause of this disorder. OBJECTIVES: The objective of this study is to present the different clinical manifestations of RVCL in three-related patients and to investigate the presence of TREX1 mutation in the extended genealogy. METHODS: Multidisciplinary testing was performed in three related patients. Based on their family history, the study was extended to 34 relatives from the same small community. Neurological evaluation, sequencing of TREX1, and presymptomatic diagnosis were offered to all participants. RESULTS: The patients exhibited the heterozygous TREX1 mutation p.V235Gfs*6, but with phenotypic variability. In addition, 15 relatives were identified as pre-manifest mutation carriers. The remaining participants did not carry the mutation. CONCLUSIONS: This is the figrst report of a large Mexican genealogy with RVCL, where the same TREX1 mutation causes a variation in organ involvement and clinical progression. The early identification and follow-up of individuals at risk may help provide insights into the basis for this variability in presentation.

Retinal vasculopathy in patients with systemic lupus erythematosus.

A retrospective case control study was conducted in the Peking Union Medical College Hospital. Medical records were reviewed for demographic data, clinical features, laboratory results, systemic lupus erythematosus (SLE) disease activity evaluations, and ophthalmic examinations to investigate the clinical characteristics and significance of retinal vasculopathy (RV) in Chinese patients with systemic lupus erythematosus. The prevalence of RV was approximately 0.66% (35/5298) in SLE patients. A total of 60 eyes were involved. The ocular presentations included decrease of visual acuity (48/60, 80%), visual field loss (7/60, 11.7%), and diplopia (3/60, 5%). Ophthalmic fundoscopic examination revealed cotton-wool spots (30/60, 50%), retinal vascular attenuation (31/60, 51.6%), and hemorrhages (41/60, 68.3%). Retinal angiogram showed that 72.7% (16/22) eyes had vaso-occlusion. The ophthalmic episodes could occur at any stage of SLE duration, with a median of 12 months (0-168 months) following SLE onset. Twenty-one (35%) eyes did not recover, or even worsened, during hospital stay. RV was found to be significantly associated with neuropsychiatric lesions (51.4% vs. 21.3%, p = .005) and hematological disturbance (62.9% vs. 34.3%, p = .005). SLE patients with RV had significantly higher SLE disease activity index scores than controls (19.9 ± 0.9 vs. 10.2 ± 0.7, p < .001). An inverse association of anti-SSA antibody with RV was detected (34.3% vs. 67.1%, p = .001). Nervous system disturbance (odds ratio (OR) = 4.340, 95% confidence interval (CI) 1.438, 13.094, p = .009) and leukocytopenia (OR = 6.385, 95% CI 1.916, 21.278, p = .003) were independent risk factors, while anti-SSA antibody positivity (OR = 0.249, 95% CI 0.087, 0.710, p = .009) was a protective factor for RV in SLE patients. In certain cases, RV is a threatening condition for SLE patients presenting with clinical ocular manifestations. Ophthalmo-fundoscopic detection is recommended as soon as SLE is diagnosed.

Multimodal Structural and Functional Characterization of Retinal Vasculopathy with Cerebral Leukoencephalopathy.

OBJECTIVE: To describe and quantify the structural and functional consequences of retinal vasculopathy with cerebral leukoencephalopathy (RVCL) on the neurosensory retina. DESIGN: Cross sectional descriptive study from December 2021 to December 2022. PARTICIPANTS: Retinal vasculopathy with cerebral leukoencephalopathy patients (n = 9, 18 eyes) recruited from the RVCL Research Center at Washington University in St. Louis. METHODS: Retinal vasculopathy with cerebral leukoencephalopathy patients underwent comprehensive ophthalmological evaluation including OCT, OCT angiography (OCTA), ultrawidefield fundus imaging, retinal autofluorescence, dark adaptation, electroretinography (ERG), Goldmann kinetic perimetry, and fluorescein angiography (FA). MAIN OUTCOME MEASURES: Comprehensive characterization from various modalities including best-corrected visual acuity, central subfield thickness (µm) from OCT, foveal avascular zone (mm2) from OCTA, dark adaptation rod intercept (seconds), cone response in ERG, and presence or absence of vascular abnormalities, leakage, neovascularization, and nonperfusion on FA. RESULTS: A total of 18 eyes from 9 individuals were included in this study. The best-corrected visual acuity ranged from 20/15 to 20/70. The mean central subfield thickness from OCT was 275.8 µm (range, 217-488 µm). The mean foveal avascular zone (FAZ) from OCTA was 0.65 (range, 0.18-1.76) mm2. On dark adaptometry, the mean time was 5.02 (range, 2.9-6.5) minutes, and 1 individual had impaired dark adaptation. Electroretinography demonstrated mild cone response impairment in 4 eyes. On FA, there was evidence of macular and peripheral capillary nonperfusion in 16 of 18 eyes and notable areas of vascular leakage and retinal edema in 5 of the 18 eyes. CONCLUSIONS: This study illustrates the phenotypic spectrum of disease and may be clinically valuable for aiding diagnosis, monitoring disease progression, and further elucidating the pathophysiology of RVCL to aid in the development of therapies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Imbalance of the von Willebrand Factor - ADAMTS-13 axis in patients with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S).

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an ultra-rare, autosomal-dominant small vessel disease caused by loss-of-function variants in the gene TREX1. Recently, elevated serum levels of von Willebrand Factor Antigen (vWF-Ag) pointed to an underlying endotheliopathy, and microvascular ischemia was suggested to contribute to the neurodegeneration in RVCL-S. Aim of this study was to further elucidate the endotheliopathy in RVCL-S. METHODS: vWF-Ag and ADAMTS-13 activity were repeatedly measured in two patients with genetically confirmed RVCL-S. Renal biopsy of both RVCL-S patients and autoptic brain, renal, hepatic, and pulmonary specimen of one patient with RVCL-S were examined immunohistochemically in comparison to matched controls. In addition, cerebral methylome analysis was performed in the autoptic brain specimen calculating differentially methylated positions compared to controls. RESULTS: While vWF-Ag and activity was strongly elevated, ADAMTS-13 activity was low in RVCL-S and further decreased over the course of the disease. Autoptic brain specimen showed signs of thromboinflammation in cerebral small vessels, and vWF-Ag staining was strongly positive in cerebral and renal small vessels in RVCL-S, while only a light to moderate vWF-Ag staining was found in controls. Cerebral methylome analysis yielded 115 differentially methylated CpGs (p < 0.05) in the deceased RVCL-S patient compared to the eight controls without brain pathology. One of the hypomethylated genes coded for ADAMTS-13 (p = 0.00056). CONCLUSIONS: These findings point to an imbalance of the vWF - ADAMTS-13 axis in patients with RVCL-S, that may finally lead to an accumulation of vWF-Ag in renal and cerebral small vessels. Elevated vWF-Ag levels may serve as an early serum marker reflecting disease activity. If confirmed, therapeutic approaches might aim at an inhibition of vWF-Ag or increase of ADAMTS-13 activity in the future.

NFL and GFAP in (pre)symptomatic RVCL-S carriers: a monogenic cerebral small vessel disease.

BACKGROUND: Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as biomarkers for cerebral small vessel disease (SVD). We investigated their role in a hereditary SVD model, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S). METHODS: NfL and GFAP levels of 17 pre-symptomatic, 22 symptomatic RVCL-S mutation carriers and 69 controls were measured using a Simoa assay. We assessed the association of serum and cerebrospinal fluid (CSF) levels of NfL and GFAP with RVCL-S symptomatology and neuropsychological functioning. RESULTS: Serum and CSF NfL levels were higher in symptomatic RVCL-S compared to controls ≥ 45 years (33.5 pg/mL vs. 9.2 pg/mL, p < 0.01; 8.5*102 pg/mL vs. 3.9*102 pg/mL, p < 0.01, respectively). Serum NfL levels were higher in symptomatic RVCL-S than pre-symptomatic carriers (33.5 pg/mL vs. 5.9 pg/mL, p = 0.02). Pre-symptomatic RVCL-S carriers had increased CSF NfL levels compared to controls < 45 years (5.2*102 pg/mL vs. 1.9*102 pg/mL, p < 0.01). No differences were found in GFAP levels across groups, but in RVCL-S carriers higher serum levels of both NfL and GFAP were linked to poorer global cognitive functioning (ß[95%CI] = - 2.86 [- 5.58 to - 0.13], p = 0.04 and ß[95%CI] = - 6.85 [- 11.54 to - 2.15], p = 0.01, respectively) and prolonged psychomotor test times (ß[95%CI] = 6.71 [0.78-12.65], p = 0.03 and ß[95%CI] = 13.84 [3.09-24.60], p = 0.01). DISCUSSION: Higher levels of serum NfL and GFAP are associated with worse cognitive functioning in RVCL-S carriers and may serve as marker for disease progression. CSF NfL levels may serve as early marker as pre-symptomatic RVCL-S patients already show differences compared to young controls.

Bilateral Retinal Artery Occlusions and Uveitis as the First Manifestation of Crohn's Disease.

PURPOSE: To present a case of newly diagnosed Crohn's disease, in which retinal artery occlusion (RAO) with uveitis was the first clinical manifestation. CASE DESCRIPTION: A 55-year-old man presented with bilateral blurred vision, with decreased best corrected visual acuity (BCVA) to light perception (right eye, RE) and 20/40 (left eye, LE). Ophthalmological examination revealed bilateral iritis, vitritis, disc edema, and retinal vascular occlusions. Because of concurrent fever and leukocytosis, a systemic infection was highly suspected. However, whole-body imaging was unrevealing. Subsequently, the patient presented with massive bloody stool. Histopathological specimen from emergent hemicolectomy confirmed transmural granulomatous inflammation. Crohn's disease was finally diagnosed. Following treatment, the BCVA recovered to 20/40 (RE) and 20/22 (LE). The systemic condition remained stable after a 3-year follow-up. CONCLUSION: RAO with uveitis is a possible manifestation of Crohn's disease. In complex uveitis cases, clinicians should be aware of inflammatory bowel diseases as an important differential diagnosis.

Progressive macular ischemia in retinal vasculopathy with cerebral leukodystrophy.

PURPOSE: We present a case of retinal vasculopathy with cerebral leukodystrophy and review the usefulness of optical coherence tomography angiography (OCT-A) in the assessment of long-term outcomes. CASE DESCRIPTION: A 31-year-old woman developed sudden-onset scotoma in her right eye. Fundus examination and fluorescein angiography showed a patch of soft exudate and capillary nonperfusion in the posterior pole and outside the vascular arcades. OCT-A revealed that the initial vessel density (VD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the right eye were 32% and 49.2%, respectively. Interestingly, over time, the VD of the SCP and DCP gradually decreased to 23.1% and 26.2%, respectively. In contrast, the initial VD of the SCP and DCP of the left eye were both stable at 44.3% and 56.2%, respectively, and only decreased slightly to 39.3% and 45.7%, respectively, over time. The average VD loss of the SCP and DCP, assessed over 1 year, was 8% and 13%, respectively, in the right eye, and 3% and 6%, respectively, in the left eye. CONCLUSION: Based on this case report, in which we demonstrated a long-term decline in VD of the macula in a young woman with mild retinal vasculopathy with cerebral leukodystrophy, we suggest that there is a potential and valuable role for OCT-A in this rare disease.

Adult-onset Coats disease.

Coats disease is an idiopathic retinal vasculopathy characterized by telangiectasia and aneurysm of retinal vessels along with intra and subretinal exudation and fluid. While Coats disease is classically described in young male population, there is an adult variant of Coats disease presenting in adulthood. Adult onset Coats disease have a similar presentation but a slower progression, localised lipid deposition, both peripheral and juxta-macular involvement. In this review article, we have attempted to describe in detail the characteristic clinical features, pathogenesis, investigation modalities and treatment in adult-onset Coats disease.

Genetic evaluation in phenotypically discordant monozygotic twins with Coats Disease.

PURPOSE: To report the unique case of a pair of phenotypically discordant monozygotic twins, with one of them affected by unilateral Coats disease. CASE REPORT: Both patients underwent a complete ophthalmologic evaluation and were genetically tested with whole-exome sequencing (WES). Any known or unknown potential genetic determinant of Coats disease wasn't found. CONCLUSION: It may suggest a non-genetic etiology for this disorder. This represents, to the best of our knowledge, the first case of genetic analysis of monozygotic twins, one of whom is affected by Coats disease. Further studies are warranted, including performing genetic analysis directly on retinal biopsy tissue.

TREX1 p.A129fs and p.Y305C variants in a large multi-ethnic cohort of CADASIL-like unrelated patients.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) are the most common forms of rare monogenic early-onset cerebral small vessel disease and share clinical, and, to different extents, neuroradiological and neuropathological features. However, whether CADASIL and RVCL-S overlapping phenotype may be explained by shared genetic risk or causative factors such as TREX1 coding variants remains poorly understood. To investigate this intriguing hypothesis, we used exome sequencing to screen TREX1 protein-coding variability in a large multi-ethnic cohort of 180 early-onset independent familial and apparently sporadic CADASIL-like Caucasian patients from the USA, Portugal, Finland, Serbia and Turkey. We report 2 very rare and likely pathogenic TREX1 mutations: a loss of function mutation (p.Ala129fs) clustering in the catalytic domain, in an apparently sporadic 46-year-old patient from the USA and a missense mutation (p.Tyr305Cys) in the well conserved C-terminal region, in a 57-year-old patient with positive family history from Serbia. In concert with recent findings, our study expands the clinical spectrum of diseases associated with TREX1 mutations.

Artificial Intelligence for Evaluation of Retinal Vasculopathy in Facioscapulohumeral Dystrophy Using OCT Angiography: A Case Series.

Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy with a wide range of manifestations including retinal vasculopathy. This study aimed to analyse retinal vascular involvement in FSHD patients using fundus photographs and optical coherence tomography-angiography (OCT-A) scans, evaluated through artificial intelligence (AI). Thirty-three patients with a diagnosis of FSHD (mean age 50.4 ± 17.4 years) were retrospectively evaluated and neurological and ophthalmological data were collected. Increased tortuosity of the retinal arteries was qualitatively observed in 77% of the included eyes. The tortuosity index (TI), vessel density (VD), and foveal avascular zone (FAZ) area were calculated by processing OCT-A images through AI. The TI of the superficial capillary plexus (SCP) was increased (p < 0.001), while the TI of the deep capillary plexus (DCP) was decreased in FSHD patients in comparison to controls (p = 0.05). VD scores for both the SCP and the DCP results increased in FSHD patients (p = 0.0001 and p = 0.0004, respectively). With increasing age, VD and the total number of vascular branches showed a decrease (p = 0.008 and p < 0.001, respectively) in the SCP. A moderate correlation between VD and EcoRI fragment length was identified as well (r = 0.35, p = 0.048). For the DCP, a decreased FAZ area was found in FSHD patients in comparison to controls (t (53) = -6.89, p = 0.01). A better understanding of retinal vasculopathy through OCT-A can support some hypotheses on the disease pathogenesis and provide quantitative parameters potentially useful as disease biomarkers. In addition, our study validated the application of a complex toolchain of AI using both ImageJ and Matlab to OCT-A angiograms.

Retinal Vasculopathy With Cerebral Leukoencephalopathy and Systemic Manifestations: Critical Role of Retina Specialists.

Purpose: To describe a case of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) to enhance early recognition of this often-missed diagnosis. Methods: A case report is presented. Results: A 50-year-old woman with a history of Raynaud phenomenon, memory difficulties, and a family history of strokes was referred for evaluation of a bilateral, small-vessel, occlusive disease refractory to immunosuppressive therapy. An extensive workup for treatable causes was unrevealing. Fifteen months after presentation, brain imaging showed white-matter lesions and dystrophic calcification, which led to the discovery of a pathogenic variant in TREX1 and the diagnosis of RVCL-S. Conclusions: Retina specialists play a critical role in the timely diagnosis of RVCL-S. Although the findings in this condition can mimic those in other common retinal vascular disorders, there are key characteristics that increase the suspicion for RVCL-S. Early recognition might decrease unnecessary therapies and procedures.

Eales' disease: epidemiology, diagnostic and therapeutic concepts.

BACKGROUND: To describe the epidemiological traits, clinical characteristics, diagnostic procedures, therapeutic interventions and evolution in a large series of patients with diagnosis of Eales' disease. METHODS: A clinical retrospective review of patients with Eales' disease, evaluated and treated between April 2009 and April 2018, with a 1-year minimum follow-up. Thirty patients (59 eyes), were included. Age, sex, laboratory results (CBC, glycemia, protein electrophoresis, ACE levels) immunological profile and a Quantiferon-TB Gold Plus test were recorded. The patients were divided into groups according to their evolution, medical or surgical treatment, and visual outcomes. RESULTS: Seventeen male patients and 13 female patients were included, and their ages ranged from 14 to 35 years. The Quantiferon-TB Gold Plus test was positive in 25 patients. Twenty-eight patients had unilateral vitreous hemorrhage, 10 of whom presented with vasculitis and non-perfusion areas in the contralateral eye, 9 presented contralateral peripheral neovascularization and 9 had contralateral fibrovascular proliferation. The remaining 2 patients presented with a rhegmatogenous retinal detachment. In 6 patients, conservative treatment with intravitreal anti-VEGF injections and photocoagulation was performed after the hemorrhage cleared. Twenty-two patients, required vitrectomy, with good visual outcomes. Macular edema was found in 16 eyes, which responded to periocular and/or systemic corticosteroid therapy, except for 9 eyes that required intravitreal bevacizumab, with complete resolution in 7 eyes and partial resolution in 2 eyes. CONCLUSIONS: Eales' disease is a pathology of significant prevalence in our country. The distribution according to sex, tends to be equivalent. The etiology, even when it is not specifically determined, according to laboratory tests, confirms the probable immunologic response in the presence of Mycobacterium tuberculosis antigens. This is still a diagnosis of exclusion, and therefore, it is advisable to perform a complete laboratory work-up in each case. Timely application of laser and other medical treatments, help to avoid progression to more advanced stages and their complications. The surgical treatment of vitrectomy for vitreous hemorrhage, and/or tractional vitreous detachment yields good primary anatomical and functional outcomes. Secondary macular edema responds to periocular and intravitreal corticosteroids, and in refractory cases, the use of anti-VEGF therapy leads to an effective resolution.

Two-step widefield fundus fluorescein angiography-assisted laser photocoagulation in pediatric retinal vasculopathy: A pilot study.

Purpose: To introduce the procedures of two-step fundus fluorescein angiography (FFA) and evaluate its utility in the management of pediatric retinal vasculopathy. Materials and methods: In this retrospective study, medical records of 12 patients who received two-step FFA were studied. The two-step FFA consisted of step 1 [low-dose (LD)] FFA at an intravenous dose of 1.5 mg/kg fluorescein, followed by step 2 [reduced dose (RD)] FFA at a dose of 6.2 mg/kg fluorescein. Demographic data, including age, gender, diagnosis, weight, gestational age, birth weight, and weight on the examination day were taken, were collected. The results of two-step FFA and treatment were recorded. Results: A total of 20 eyes were studied. The top 5 common FFA changes in RD-FFA included peripheral avascular zone (15 eyes), fluorescein leakage (10 eyes), supernumerous vascular branching (10 eyes), neovascularization (NV) (8 eyes), and absence of the foveal avascular zone (6 eyes). LD-FFA was efficient to show all the NV without severe vitreous dye in 8/8 (100.0%) eyes with NV, partial peripheral avascular zone in 11/15 (73.3%) eyes, while RD-FFA always offered more information in all the eyes. Thirteen eyes had laser photocoagulation under the guidance of LD-FFA. In 4 (30.8%) eyes, RD-FFA revealed more lesions and an immediate relaser was performed. Laser photocoagulation was successfully performed in all the 13 eyes in one session without being rearranged. After a median follow-up of 28.1 months, all the eyes were in a stable status. Conclusion: Step-one LD-FFA acted as a pre-FFA to show the NV, and step-two RD-FFA acted as a double-check. The modified strategy may be a helpful clinical adjuvant in the laser photocoagulation of pediatric retinal disorders, especially for young ophthalmologists.