RESUMO
BACKGROUND: To elucidate the relationship between inherited retinal disease, visual acuity and refractive error development in Asian patients. SUBJECTS: Five hundred phakic eyes with refractive data were analysed in this retrospective cohort. Diseases were categorized by clinical phenotypes, and the prevalent genotypes identified in the Taiwan Inherited Retinal Degeneration Project were analysed. Consecutive surveys in Taiwan have provided the rates of myopia in the general population. RESULTS: No differences were observed among the disease phenotypes with respect to myopia (P = 0.098) and high myopia rates (P = 0.037). The comparison of refractive error between retinitis pigmentosa and diseases mainly affecting the central retina showed no difference, and the refraction analyses in diseases of different onset ages yielded no significance. Moreover, there was no difference in the myopia rate between the diseases and general population. Among the genotypes, a higher spherical equivalent was seen in RPGR and PROM1-related patients and emmetropic trends were observed in patients with CRB1 and PRPF31 mutations. Furthermore, significantly poorer visual acuity was found in ABCA4, CRB1 and PROM1-related patients, and more preserved visual acuity was seen in patients with EYS, USH2A, and RDH12 mutations. CONCLUSIONS: No significant differences were observed in visual acuity, refractive state and myopia rate between patients with inherited retinal disease and the general population, and different subtypes of inherited retinal disease shared similar refractive state, except for higher cylindrical dioptres found in patients with Leber's congenital amaurosis. The heterogeneity of disease-causing genes in Asian patients may lead to variable refractive state.
RESUMO
Numerous evidence suggests coronavirus disease 2019 (COVID-19) potentially triggers demyelinating diseases, inclusive of multiple sclerosis (MS), and acute disseminated encephalomyelitis (ADEM), and various mechanisms have been proposed. We report a 42-year-old male presented with bilateral optic neuritis and encephalopathy, 2 weeks following COVID-19 infection. He denied any history or family history of neurological and ocular diseases. Severe bilateral visual impairment (only light perception) and pain with eye movement were reported. Fundoscopy revealed bilateral optic disc swelling. Magnetic resonance imaging showed tortuous bilateral optic nerves with optic nerve and nerve sheath enhancement. Multiple hyperintense nodules in bilateral cerebral white matter were noted on fluid-attenuated inversion recovery T2-weighted imaging without diffusion restriction or gadolinium contrast enhancement. Hypointense nodules in cerebral white matter were also noted on T1-weighted imaging, which implied some old lesions. Dissemination in space and time and cerebrospinal fluid-specific oligoclonal bands confirmed the diagnosis of MS. Both serum aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies were negative. He received pulse steroid therapy for 5 days, followed by slowly tapering oral prednisolone. His vision, ocular motion pain, and encephalopathy improved gradually. However, the visual outcome was still poor (bilateral 20/400), and optic atrophy was noticed during 1-year follow-up. To our knowledge, this is the first case of MS following severe acute respiratory syndrome coronavirus 2 infection presented with bilateral optic neuritis and encephalopathy. Since these manifestations are exceedingly rare in MS, we suspect acute immune reactions induced by COVID-19 could bring about the atypical ADEM-like presentations of MS.
RESUMO
BACKGROUND: Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous studies. This study provided a deeper understanding of the detailed clinical features using multimodal imaging, genetic spectrum, and genotype-phenotype correlations of USH2A-related retinal dystrophies in Taiwan. RESULTS: In our cohort, the mean age at first visit was 47.66 ± 13.54 years, and the mean age at symptom onset, which was referred to the onset of nyctalopia and/or visual field constriction, was 31.21 ± 15.24 years. Among the variants identified, 23 (50%) were missense, 10 (22%) were splicing variants, 8 (17%) were nonsense, and 5 (11%) were frameshift mutations. The most predominant variant was c.2802T>G, which accounted for 21% of patients, and was located in exon 13. Patients with truncated alleles had significantly earlier symptom onset and seemly poorer disease progression regarding visual acuity, ellipsoid zone line length, and hypofluorescent lesions in the macula than those who had the complete gene. However, the clinical presentation revealed similar progression between patients with and without the c.2802T>G variant. During long-term follow-up, the patients had different ellipsoid zone line progression rates and were almost evenly distributed in the fast, moderate, and slow progression subgroups. Although a younger onset age and a smaller baseline intact macular area was observed in the fast progression subgroup, the results showed no significant difference. CONCLUSIONS: This is the first cohort study to provide detailed genetic and longitudinal clinical analyses of patients with USH2A-related retinal dystrophies in Taiwan. The mutated allele frequency in exon 13 was high in Taiwan due to the predominant c.2802T>G variant. Moreover, truncated variants greatly impacted disease progression and determined the length of therapeutic windows. These findings provide insight into the characteristics of candidates for future gene therapies.
Assuntos
Éxons , Proteínas da Matriz Extracelular , Distrofias Retinianas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Éxons/genética , Proteínas da Matriz Extracelular/genética , Prevalência , Distrofias Retinianas/genética , Distrofias Retinianas/patologia , Taiwan , Síndromes de Usher/genéticaRESUMO
BACKGROUND: To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response. METHODS: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. RESULTS: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). CONCLUSIONS: Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.
Assuntos
Inibidores da Angiogênese , Estudo de Associação Genômica Ampla , Injeções Intravítreas , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Degeneração Macular Exsudativa , Humanos , Masculino , Feminino , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genética , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Idoso , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/genética , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologia , Ranibizumab/administração & dosagem , Tomografia de Coerência Óptica , Genótipo , Seguimentos , Angiofluoresceinografia , Resultado do Tratamento , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Pessoa de Meia-Idade , Predisposição Genética para Doença , Serina Peptidase 1 de Requerimento de Alta Temperatura ARESUMO
The diagnosis of inherited retinal degeneration (IRD) is challenging owing to its phenotypic and genotypic complexity. Clinical information is important before a genetic diagnosis is made. Metabolomics studies the entire picture of bioproducts, which are determined using genetic codes and biological reactions. We demonstrated that the common diagnoses of IRD, including retinitis pigmentosa (RP), cone-rod dystrophy (CRD), Stargardt disease (STGD), and Bietti's crystalline dystrophy (BCD), could be differentiated based on their metabolite heatmaps. Hundreds of metabolites were identified in the volcano plot compared with that of the control group in every IRD except BCD, considered as potential diagnosing markers. The phenotypes of CRD and STGD overlapped but could be differentiated by their metabolomic features with the assistance of a machine learning model with 100% accuracy. Moreover, EYS-, USH2A-associated, and other RP, sharing considerable similar characteristics in clinical findings, could also be diagnosed using the machine learning model with 85.7% accuracy. Further study would be needed to validate the results in an external dataset. By incorporating mass spectrometry and machine learning, a metabolomics-based diagnostic workflow for the clinical and molecular diagnoses of IRD was proposed in our study.
Assuntos
Aprendizado de Máquina , Metabolômica , Degeneração Retiniana , Retinose Pigmentar , Doença de Stargardt , Humanos , Metabolômica/métodos , Diagnóstico Diferencial , Degeneração Retiniana/diagnóstico , Degeneração Retiniana/sangue , Degeneração Retiniana/genética , Degeneração Retiniana/metabolismo , Masculino , Feminino , Retinose Pigmentar/diagnóstico , Retinose Pigmentar/genética , Retinose Pigmentar/sangue , Retinose Pigmentar/metabolismo , Doença de Stargardt/genética , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Biomarcadores/sangue , Metaboloma , Criança , Distrofias de Cones e Bastonetes/diagnóstico , Distrofias de Cones e Bastonetes/genética , Distrofias de Cones e Bastonetes/sangue , Distrofias de Cones e Bastonetes/metabolismo , Espectrometria de Massas , Degeneração Macular/sangue , Degeneração Macular/diagnóstico , Degeneração Macular/genéticaRESUMO
INTRODUCTION: To evaluate the efficacy and safety of myopia control using a multifocal soft contact lens designed with high peripheral add power in schoolchildren. METHODS: This 1-year multi-center, prospective, randomized, double-blind, controlled study enrolled myopic schoolchildren aged 6-15 years with refractive errors between - 1.0 D and - 10.0 D. Each participant was randomly allocated to wear a daily disposable multifocal soft contact lens as the treatment in one eye and a single-vision soft contact lens as the control in the other eye. The primary endpoints were changes in the cycloplegic spherical equivalent (SE) and axial length at 1 year. RESULTS: Fifty-two of the 59 participants (88.1%) completed the study protocol. The mean change in SE was - 0.73 ± 0.40 D in the treatment group. and - 0.85 ± 0.51 D in the control group (mean difference: - 0.12 ± 0.34 D, p = 0.012). The mean change in axial length was 0.25 ± 0.14 mm in the treatment group, and 0.33 ± 0.17 mm in the control group (mean difference: 0.08 ± 0.10 mm, p < 0.001). The treatment was well tolerated, and no serious adverse events were observed. CONCLUSIONS: Treatment with multifocal soft contact lenses with high peripheral add power was effective in controlling the progression of myopia and axial length elongation in myopic schoolchildren.
RESUMO
Angelman syndrome, a severe neurodevelopmental disorder, is primarily caused by mutations or deletions of maternally inherited ubiquitin protein ligase E3A (UBE3A). Activation of the silenced paternal copy of UBE3A can occur with pharmacological perturbation; however, an environmental approach has not been examined. Here, we found Ube3a is highly expressed in embryonic and early neonatal mouse retina and is maternally-, but not paternally-, expressed in ganglion cells, amacrine cells, and horizontal cells. Moreover, we analyzed UBE3A expression in the retina and visual cortex of postnatal day 28 mice (P28) following exposure to light emissions from white compact-fluorescent bulbs or blue light-emitting diodes from postnatal day 0 (P0) to 28 (P28), encompassing a crucial phase of visual system development. We found higher levels of Ube3a RNA and protein in the retina, but not visual cortex compared with tissues from P28 mice exposure to typical lighting (controls). Levels of both paternal- and maternal-UBE3A protein in mouse retina were higher than controls in P28 mice exposed to white or blue light. Moreover, levels of open and repressive chromatin structures, indicated by histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3), respectively, were increased in the Ube3a promoter from mouse retina exposed to white or blue light. Our findings strongly suggest that extended exposure to white or blue light constitutes a substantial environmental factor that can effectively promote UBE3A expression within the central nervous system.
Assuntos
Síndrome de Angelman , Camundongos , Animais , Síndrome de Angelman/genética , Síndrome de Angelman/metabolismo , Histonas , Cromatina , Lisina , Retina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
The cause of trigger fingers remains uncertain. High lipid levels in the blood may reduce blood supply to the distal fingers and promote inflammation. We aimed to explore the association between hyperlipidemia and trigger finger. A nationwide population-based cohort study using longitudinal data from 2000 to 2013, 41,421 patients were included in the hyperlipidemia cohort and 82,842 age- and sex-matched patients were included in the control cohort. The mean age was 49.90 ± 14.73 years in the hyperlipidemia cohort and 49.79 ± 14.71 years in the control cohort. After adjusting for possible comorbidities, the hazard ratio of trigger finger in the hyperlipidemia cohort was 4.03 (95% confidence interval [CI], 3.57-4.55), with values of 4.59 (95% CI, 3.67-5.73) and 3.77 (95% CI, 3.26-4.36) among male and female patients, respectively. This large-scale population-based study demonstrated that hyperlipidemia is correlated to trigger finger.
Assuntos
Hiperlipidemias , Dedo em Gatilho , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Hiperlipidemias/complicações , Hiperlipidemias/epidemiologia , Estudos de Coortes , Comorbidade , Inflamação , Taiwan , Estudos Retrospectivos , Fatores de Risco , IncidênciaRESUMO
Drought, as a widespread environmental factor in nature, has become one of the most critical factors restricting the yield of forage grass. Sudangrass (Sorghum sudanense (Piper) Stapf.), as a tall and large grass, has a large biomass and is widely used as forage and biofuel. However, its growth and development are limited by drought stress. To obtain novel insight into the molecular mechanisms underlying the drought response and excavate drought tolerance genes in sudangrass, the first full-length transcriptome database of sudangrass under drought stress at different time points was constructed by combining single-molecule real-time sequencing (SMRT) and next-generation transcriptome sequencing (NGS). A total of 32.3 Gb of raw data was obtained, including 20,199 full-length transcripts with an average length of 1628 bp after assembly and correction. In total, 11,921 and 8559 up- and down-regulated differentially expressed genes were identified between the control group and plants subjected to drought stress. Additionally, 951 transcription factors belonging to 50 families and 358 alternative splicing events were found. A KEGG analysis of 158 core genes exhibiting continuous changes over time revealed that 'galactose metabolism' is a hub pathway and raffinose synthase 2 and ß-fructofuranosidase are key genes in the response to drought stress. This study revealed the molecular mechanism underlying drought tolerance in sudangrass. Furthermore, the genes identified in this study provide valuable resources for further research into the response to drought stress.
RESUMO
Straw return in rice (Oryza sativa L.) paddy has been heavily criticized for its potential to influence ammonia (NH3) volatilization loss due to irrational fertilizer N application. Therefore, improving the N fertilization strategies within residue straw systems is necessary to reduce N loss from NH3 volatilization. This study investigated how the incorporation of oilseed rape straw and the urease inhibitor affected NH3 volatilization, fertilizer N use efficiency (FNUE), and rice yields over two growing seasons (2018-2019) in the purple soil region. This study arranged eight treatments combined straw (2, 5, 8 ton ha-1, named 2S, 5S, 8S, respectively), with urea or urease inhibitor (UI, 1% NBPT) with three replicates, which included control (CK), UR (Urea, 150 kg N ha-1), UR + 2S, UR + 5S, UR + 8S, UR + 2S + UI, UR + 5S + UI, UR + 8S + UI, based on the randomized complete block method. Our results indicated that incorporating oilseed rape straw increased NH3 losses by 3.2-30.4% in 2018 and 4.3-17.6% in 2019 than the UR treatment, attributing to the higher NH4+-N content and pH value within floodwater. However, the UR + 2S + UI, UR + 5S + UI and UR + 8S + UI treatments reduced NH3 losses by 3.8%, 30.3%, and 8.1% in 2018 and 19.9%, 39.5%, and 35.8% in 2019, separately compared to their corresponding UR plus straw treatments. According to the findings, adding 1% NBPT significantly decreased NH3 losses while incorporating 5 ton ha-1 oilseed rape straw. Furthermore, adding straw, either alone or in conjunction with 1% NBPT, increased rice yield and FNUE by 0.6-18.8% and 0.6-18.8%, respectively. Otherwise, NH3 losses scaled by yield in the UR + 5S + UI treatment decreased significantly between all treatments in 2018 and 2019. These results suggest that optimizing the oilseed rape straw rate combined with 1% NBPT applied with urea efficiently increased rice yield and reduced NH3 emissions in the purple soil region of Sichuan Province, China.
RESUMO
BACKGROUND: Optic neuritis (ON) is an inflammatory disease of optic nerve. The distinct etiologies of ON significantly influence its clinical manifestation, neuroimaging findings, and visual outcomes. However, the clinical characteristics might be influenced by the racial differences. The purpose of this study is to investigate the clinical characteristics of various types of ON at a Taiwanese tertiary center. METHODS: This cohort study analyzed 163 patients who received treatment and continued following-up for ON between 2015 and 2022. We selected patients who had been tested for anti-aquaporin-4 antibody (AQP4-Ab) and anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab). The participants were classified into four groups on the basis of their etiologies, specifically (1) multiple sclerosis (MS)-related, (2) AQP4-Ab-positive, (3) MOG-Ab-positive, or (4) idiopathic ON. The researchers recorded the patients' clinical characteristics, treatment course, magnetic resonance imaging and optical coherence tomography (OCT) findings, and visual outcomes. RESULTS: MOG-Ab-positive group had higher percentages of disk swelling and pain with eye movement. Long optic nerve and perineural enhancement are the hallmarks of MOG-Ab-related ON. The ON relapse rate was higher in AQP4-Ab-positive group. Although members of AQP4-Ab-positive group received immediate steroid pulse therapy, these patients experienced the worst visual outcomes. Moreover, a thinner retinal nerve fiber layer (RNFL) was noted in AQP4-Ab-positive group. MS group had a higher incidence of extra-optic nerve lesions. Multivariate regression identified pretreatment visual acuity and RNFL thickness as the important factors affecting visual outcomes. CONCLUSIONS: This cohort study identified the clinical features of different types of ON. Patients with AQP4-Ab-positive ON had poorer visual outcomes, which may be attributed to multiple relapses and profound nerve damage, as revealed by OCT findings. Patients with MOG-Ab-positive ON displayed long optic nerve enhancement but had more favorable prognoses. Thus, antibody-based classification facilitates treatment and prognosis in ON.
Assuntos
Autoanticorpos , Neurite Óptica , Humanos , Estudos de Coortes , Taiwan/epidemiologia , Aquaporina 4 , Glicoproteína Mielina-Oligodendrócito , Neurite Óptica/diagnóstico por imagem , Neurite Óptica/epidemiologia , Neurite Óptica/tratamento farmacológico , PrognósticoRESUMO
Precise genome manipulation in specific cell types and subtypes in vivo is crucial for neurobiological research because of the cellular heterogeneity of the brain. Site-specific recombinase systems in the mouse, such as Cre-loxP, improve cell type-specific genome manipulation; however, undesirable expression of cell type-specific Cre can occur. This could be due to transient expression during early development, natural expression in more than one cell type, kinetics of recombinases, sensitivity of the Cre reporter, and disruption in cis-regulatory elements by transgene insertion. Moreover, cell subtypes cannot be distinguished in cell type-specific Cre mice. To address these issues, we applied an intersectional genetic approach in mouse using triple recombination systems (Cre-loxP, Flp-FRT and Dre-rox). As a proof of principle, we labelled heterogeneous cell subtypes and deleted target genes within given cell subtypes by labelling neuropeptide Y (NPY)-, calretinin (calbindin 2) (CR)- and cholecystokinin (CCK)-expressing GABAergic neurons in the brain followed by deletion of RNA-binding Fox-1 homolog 3 (Rbfox3) in our engineered mice. Together, our study applies an intersectional genetic approach in vivo to generate engineered mice serving dual purposes of simultaneous cell subtype-specific labelling and gene knockout.
Assuntos
Integrases , Recombinases , Camundongos , Animais , Técnicas de Inativação de Genes , Integrases/metabolismo , Recombinases/genética , Recombinases/metabolismo , Transgenes , Encéfalo/metabolismo , Camundongos TransgênicosRESUMO
In recent years, the excessive application of nitrogen and phosphorus fertilizers has caused serious pollution and eutrophication, especially in paddy fields. Accordingly, a two-year (2018-2019) study was conducted at a rice paddy field under different fertilizer application rates and straw mulching in Chengdu Plain. N and P losses through the rainfall and surface runoff in the paddy field were measured under natural rainfall conditions. The results showed that nitrogen mainly existed in the form of ammonium nitrogen, and phosphorus mainly existed in the form of soluble phosphorus in the wet deposition. The wet deposition of nitrogen and phosphorus mainly occurred in June, July, and August. Surface runoff was positively correlated with rainfall, whereas surface runoff nitrogen concentration was inversely correlated with rainfall. The highest runoff losses of TN (4.75 kg·hm-2 in 2018 and 2.68 kg·hm-2 in 2019) were produced by TR3 practice and were 26.73% and 43.32% higher than that of the conventional practice. TN runoff loss was significantly decreased by reducing the rate of N fertilizer (P<0.05). Compared with that in the conventional practice TR1, TR4 reduced the N loss by 36.33% in 2018 and 26.74% in 2019, respectively. Optimized fertilizer TR2 and nitrogen reduction practice TR4 decreased P loss from surface runoff, and high intensity rainfall could reduce the content of granular phosphorus in surface runoff. The surface runoff occurring in July, August, and September contributed mostly to the total N loss, whereas the loss of total P mainly occurred before July. Consequently, the use of balanced fertilizer and decreased nitrogen fertilization amount might be effective strategies to attenuate non-point source pollution in the Chengdu Plain in the paddy fields.
Assuntos
Oryza , Fósforo , Fósforo/análise , Agricultura/métodos , Nitrogênio/análise , Fertilizantes , Fertilização , Movimentos da Água , Solo , ChinaRESUMO
A 29-year-old female with treated acute lymphoblastic leukemia in remission presented with blurred vision and pain on movement of the right eye. On examination, visual acuity was 20/25 in the right eye and 20/20 in the left eye. Direct ophthalmoscopy revealed that the optic disc was swollen with peripapillary hemorrhage in the right eye. The rest of the clinical examination was within normal limits. Magnetic resonance imaging demonstrated enhancement of her right optic nerve. Lumbar puncture and bone marrow examination revealed no malignant cells. Only vitreous fluid cytology showed blast cells. Intravitreal injection of methotrexate was given, and repeated vitreous tapping was normal. The vision of her right eye remained 20/20 until 1 year later when optic disc and retinal vascular occlusion was noted. Her vision deteriorated to no light perception within 2 weeks, and optociliary shunt vessels occurred. Isolated disc swelling with positive vitreous cytology can be the first and only presentation of relapsed hematologic disorders. Infiltrative optic neuropathy should be considered in the differential diagnosis of optic disc edema. Vitreous tapping could be considered as the diagnostic procedure even if the results of lumbar puncture were negative.
RESUMO
This study investigated the impact of retinal fluid tolerance on retinal thickness and visual acuity in patients with neovascular age-related macular degeneration after 18 months of treatment using intravitreal aflibercept. This retrospective study was based on the medical records of 90 eyes presenting persistent or recurrent retinal fluid retention after 3 months of aflibercept loading injections. We defined the fluid tolerance ratio as the sum of fluid-tolerance duration divided by the total duration of retinal fluid observed throughout the follow-up period. Eyes were categorized into strict, intermediate, and relaxed group based on their fluid tolerance ratio (= 0, <30%, > = 30%, respectively). The mean total follow-up time was 556 days. The relaxed group required fewer injections than the strict group (4.92 vs 7.50 injections, P < 0.01) and presented a similar reduction in retinal thickness (-57.50 vs -71.65 µm, P = 0.83). Nonetheless, the two groups were similar in terms of final visual acuity (logarithm of the minimum angle of resolution 0.72 vs 0.70, P = 0.95) and visual gains (4.21 vs -1.12 letters, P = 0.56). These results indicate that in the setting of limited medical resources, a fluid-tolerant approach provides comparable gains in visual acuity. Reducing the number of injections may also improve adherence to therapy.
Assuntos
Degeneração Macular , Receptores de Fatores de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/uso terapêutico , Seguimentos , Humanos , Lactente , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in NOTCH3, is the most common cause of hereditary cerebral small vessel disease. Whether it will involve systemic vasculopathy such as retinal vessel remains unknown. Optical coherence tomography angiography (OCT-A) is a noninvasive technique for visualising retinal blood flow. We analysed vessel density and retinal thickness in patients with CADASIL and investigated their correlations with disease severity. METHODS: This prospective study enrolled 35 patients with CADASIL (59 eyes) and 35 healthy controls (54 eyes). OCT-A was used to measure the vessel density of the macular region and the thickness of retinal layers. Patients with CADASIL were divided into stroke (n = 20) and nonstroke (n = 15) subgroups and underwent cognition and gait speed evaluation. Neuroimaging markers of cortical thickness, white matter hyperintensity, lacunae, and cerebral microbleeds were examined through brain magnetic resonance imaging. RESULTS: The OCT-A parameters, including vessel density, were comparable between the patients with CADASIL and the controls. In patients with CADASIL, vessel density in the superficial retinal plexus in the macula as was inner retinal thickness was significantly lower in the stroke than the nonstroke subgroup. Macular vessel density and inner retinal thickness were positively correlated with gait speed, while negatively correlated with number of lacunae. CONCLUSIONS: OCT-A is potentially a useful tool for evaluating disease severity, ischaemic burden, and neurodegeneration in patients with advanced CADASIL.
Assuntos
CADASIL , Leucoencefalopatias , Acidente Vascular Cerebral , Humanos , CADASIL/patologia , Infarto Cerebral , Imageamento por Ressonância Magnética , Estudos Prospectivos , Receptor Notch3/genéticaRESUMO
The pathognomonic hallmark of Parkinson's disease (PD), α-synuclein, has been observed in the retina of PD patients. We investigated whether biomarkers in the tears and retinal microvascular changes associate with PD risk and progression. This prospective study enrolled 49 PD patients and 45 age-matched healthy controls. The α-synuclein and neurofilament light chain (NfL) levels were measured using an electrochemiluminescence immunoassay. Retinal vessel density was assessed using optical coherence tomography angiography (OCT-A). The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Mini-Mental State Examination score were used to assess motor and cognitive progression. The α-synuclein and NfL levels in the tears were higher in PD patients than in controls (α-synuclein: 55.49 ± 8.12 pg/mL vs. 31.71 ± 3.25 pg/mL, P = 0.009; NfL: 2.89 ± 0.52 pg/mL vs. 1.47 ± 0.23 pg/mL, P = 0.02). The vessel densities in the deep plexus of central macula and the radial peripapillary capillary layer of disc region were lower in PD patients with moderate-stage compared with early-stage PD (P < 0.05). The accuracy of predicting PD occurrence using age and sex alone (area under the curve [AUC] 0.612) was significantly improved by adding α-synuclein and NfL levels and retinal vascular densities (AUC 0.752, P = 0.001). After a mean follow-up of 1.5 ± 0.3 years, the accuracy of predicting motor or cognitive progression using age, sex, and baseline motor severity as a basic model was increased by incorporating retinal microvascular and biofluid markers as a full model (P = 0.001). Our results showed that retinal microvascular densities combined with α-synuclein and NfL levels in tears are associated with risk and progression of PD.
Assuntos
Densidade Microvascular , Proteínas de Neurofilamentos , Doença de Parkinson , Vasos Retinianos , alfa-Sinucleína , Biomarcadores , Humanos , Proteínas de Neurofilamentos/metabolismo , Doença de Parkinson/fisiopatologia , Estudos Prospectivos , Retina , Vasos Retinianos/fisiopatologia , Lágrimas , alfa-Sinucleína/metabolismoRESUMO
Purpose: To demonstrate the changes in the retinal nerve fiber layer (RNFL) after orbital decompression for thyroid eye disease (TED). Methods: We retrospectively enrolled 52 surgical TED patients, 30 nonsurgical TED patients, and 30 control subjects. Five surgical TED eyes with disc edema were excluded. The surgical TED patients were classified into the "dysthyroid optic neuropathy (DON)" group (16 eyes) and the "non-DON" group (83 eyes). Optical coherence tomography (OCT) and visual field (VF) examinations were performed preoperatively and 6 months later. The control subjects and nonsurgical TED patients received two OCT examinations at 6-month intervals. The postoperative changes in the RNFL thickness were compared between groups. Three cases with severe postoperative vision loss were presented additionally. Results: The changes in the RNFL thickness of the controls (0.5 ± 3.4 µm) and the nonsurgical TED patients (0.3 ± 2.8 µm) were significantly smaller than the surgical TED patients (P < 0.001). The DON group (-9.2 ± 9.2 µm) had greater RNFL thickness reduction than the non-DON group (-3.9 ± 5.4 µm) (P = 0.002). Bone removal decompression was associated with decreased RNFL in the non-DON (P = 0.025; ß = -2.49) and DON (P = 0.042; ß = -9.43) groups. Three cases who were hard to operate due to extensive fibrosis experienced severe vision loss postoperatively due to anterior ischemic optic neuropathy, posterior ischemic optic neuropathy, and posterior ciliary artery occlusion, respectively. Conclusions: TED patients experienced subclinical optic nerve injury and significant RNFL loss after the orbital decompression surgery. Aggressive manipulation during decompression surgery may lead to dreadful vision loss. Tailored surgical plans and delicate manipulation are warranted.
Assuntos
Oftalmopatia de Graves , Doenças do Nervo Óptico , Neuropatia Óptica Isquêmica , Descompressão/efeitos adversos , Oftalmopatia de Graves/cirurgia , Humanos , Nervo Óptico/diagnóstico por imagem , Nervo Óptico/cirurgia , Doenças do Nervo Óptico/complicações , Doenças do Nervo Óptico/cirurgia , Neuropatia Óptica Isquêmica/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Transtornos da VisãoRESUMO
Superior segmental optic nerve hypoplasia (SSONH) is a congenital condition characterized by developmental abnormalities of the superior optic disc and an underappreciated differential diagnosis for glaucoma. The reported prevalence is less than 1%, although likely underestimated due to the difficulties with diagnosis. The exact pathophysiology of SSONH remains elusive, but a mechanism involving developmental attrition of retinal ganglion cells has been proposed, and maternal diabetes is recognized as a major risk factor. SSONH often is observed incidentally, and the patients typically are then evaluated for an acquired optic atrophy, often glaucoma because of the presence of inferior visual field defects. There are 4 characteristic signs of SSONH: superior entrance of the central retinal artery, superior disc pallor, superior peripapillary halo, and thinning of the superior peripapillary nerve fiber layer; however, the presence of these signs is variable. Optical coherence tomography can be helpful in distinguishing SSONH by demonstrating superonasal retinal nerve fiber layer thinning, as compared to the inferotemporal thinning seen in glaucoma, and an aberrant extension of retinal pigment epithelium over Bruch membrane. Overall, the prognosis of SSONH is favorable, with a non-progressive course. It is essential that ophthalmologists recognize and differentiate SSONH from glaucoma to avoid misdiagnosis and unnecessary treatment.