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BACKGROUND: Diabetic retinopathy (DR), a chronic and progressive microvascular complication of diabetes mellitus, substantially threatens vision and is a leading cause of blindness among working-age individuals worldwide. Traditional diagnostic methods, such as ophthalmoscopy and fluorescein angiography are nonquantitative, invasive, and time consuming. Analysis of protein biomarkers in tear fluid offers noninvasive insights into ocular and systemic health, aiding in early DR detection. This study introduces a surface acoustic wave (SAW) microchip that rapidly enhances fluorescence in bead-based immunoassays for the sensitive and noninvasive DR detection from human tear samples. RESULTS: The device facilitated particle mixing for immunoassay formation and particle concentration in the droplet, resulting in an enhanced immunofluorescence signal. This detachable SAW microchip allows the disposal of the cover glass after every use, thereby improving the reusability of the interdigital transducer and minimizing potential cross-contamination. A preliminary clinical test was conducted on a cohort of 10 volunteers, including DR patients and healthy individuals. The results demonstrated strong agreement with ELISA studies, validating the high accuracy rate of the SAW microchip. SIGNIFICANCE: This comprehensive study offers significant insights into the potential application of a novel SAW microchip for the early detection of DR in individuals with diabetes. By utilizing protein biomarkers found in tear fluid, the device facilitates noninvasive, rapid, and sensitive detection, potentially revolutionizing DR diagnostics and improving patient outcomes through timely intervention and management of this vision-threatening condition.
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Retinopatía Diabética , Lágrimas , Humanos , Lágrimas/química , Retinopatía Diabética/diagnóstico , Inmunoensayo/métodos , Sonido , Técnicas Biosensibles/instrumentación , Biomarcadores/análisis , Propiedades de SuperficieRESUMEN
OBJECTIVES: Anti-vascular endothelial growth factor (VEGF) therapy restores retinal architecture and enhances vision in diabetic macular edema (DME). Bevacizumab is an off-label anti-VEGF drug that effectively treats DME. The safety and efficacy of bevacizumab biosimilars, which are more affordable than the original medication, still need to be established. This study aimed to assess the cost-effectiveness, efficacy, and safety of biosimilars for treating patients with naïve DME across various price ranges that are accessible in the Indian market. MATERIALS AND METHODS: Two biosimilars, BevaciRelTM (Reliance Life Sciences Pvt. Ltd.) and ZyBev (Cadila Healthcare Limited), were compared to their original, Avastin (Roche Products [India] Pvt. Ltd.), in a randomized, control study. Three end-notes were used to assess safety and efficacy: persistence, improvement, and adverse events. Cost-effective analysis was carried out using a decision-tree analysis model. RESULTS: This study included 69 (59%) men and 54 (41%) women with naïve DME. The cohort had an average log MAR visual acuity of 0.87 ± 0.22, and the central retinal thickness at baseline on OCT was 398.5 ± 37.61 µm. The visual acuity showed a similar improvement, and there was a decrease in central retinal thickness as observed on OCT across the groups. The incremental cost-effectiveness ratio was 10.8. CONCLUSIONS: The biosimilars of bevacizumab are safe and efficacious in treating DME in a cost-effective manner.
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Inhibidores de la Angiogénesis , Bevacizumab , Biosimilares Farmacéuticos , Análisis Costo-Beneficio , Retinopatía Diabética , Edema Macular , Humanos , Bevacizumab/uso terapéutico , Bevacizumab/economía , Edema Macular/tratamiento farmacológico , Biosimilares Farmacéuticos/economía , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Masculino , Femenino , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/economía , Inhibidores de la Angiogénesis/economía , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/administración & dosificación , Persona de Mediana Edad , Resultado del Tratamiento , Anciano , Agudeza Visual , India , AdultoRESUMEN
Early detection of diabetic retinopathy (DR) is an urgent ophthalmological problem in Russia and globally. PURPOSE: This study assesses the prevalence of asymptomatic retinopathy and attempts to identify risk groups for its development in patients with type 1 and 2 diabetes mellitus (T1DM and T2DM). MATERIAL AND METHODS: The study involved clinics from 5 cities in the Russian Federation and it included 367 patients with DM, 34.88% men and 65.12% women, aged 50.88±20.55 years. 34.88% of patients suffered from T1DM, 65.12% suffered from T2DM, the average duration of the disease was 9.02±7.22 years. 58.31% of patients had a history of arterial hypertension, 13.08% had a history of smoking. The primary endpoint was the frequency of detection of diabetic changes in the eye fundus of patients with T1DM and T2DM in general; the secondary endpoint - same but separately, and for T2DM patients depending on the duration of the disease. The exploratory endpoint was the assessment of the influence of various factors on the development of DR. The patients underwent visometry (modified ETDRS table), biomicroscopy, mydriatic fundus photography according to the «2 fields¼ protocol. RESULTS: The average detection rate of DR was 12.26%, primarily observed in patients with T2DM (13.81%), women (9.26%), in both eyes (8.17%). Among patients with DR, 26 (19.55%) had glycated hemoglobin (HbA1c) level exceeding 7.5% (p=0.002), indicating a direct relationship between this indicator and the incidence of DR. Logistic regression analysis showed that the duration of diabetes of more than 10 years has a statistically significant effect on the development of DR. In the modified model for odds estimation, the likelihood of developing DR is increased by the duration of DM for more than 10 years; increased blood pressure; HbA1c level >7.5%. CONCLUSION: The obtained results, some of which will be presented in subsequent publications, highlight the effectiveness of using two-field mydriatic fundus photography as a screening for DR.
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Fondo de Ojo , Fotograbar , Humanos , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Federación de Rusia/epidemiología , Prevalencia , Fotograbar/métodos , Adulto , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Anciano , Factores de Riesgo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/diagnóstico , Diagnóstico PrecozRESUMEN
Importance: Safe integration of artificial intelligence (AI) into clinical settings often requires randomized clinical trials (RCT) to compare AI efficacy with conventional care. Diabetic retinopathy (DR) screening is at the forefront of clinical AI applications, marked by the first US Food and Drug Administration (FDA) De Novo authorization for an autonomous AI for such use. Objective: To determine the generalizability of the 7 ethical research principles for clinical trials endorsed by the National Institute of Health (NIH), and identify ethical concerns unique to clinical trials of AI. Design, Setting, and Participants: This qualitative study included semistructured interviews conducted with 11 investigators engaged in the design and implementation of clinical trials of AI for DR screening from November 11, 2022, to February 20, 2023. The study was a collaboration with the ACCESS (AI for Children's Diabetic Eye Exams) trial, the first clinical trial of autonomous AI in pediatrics. Participant recruitment initially utilized purposeful sampling, and later expanded with snowball sampling. Study methodology for analysis combined a deductive approach to explore investigators' perspectives of the 7 ethical principles for clinical research endorsed by the NIH and an inductive approach to uncover the broader ethical considerations implementing clinical trials of AI within care delivery. Results: A total of 11 participants (mean [SD] age, 47.5 [12.0] years; 7 male [64%], 4 female [36%]; 3 Asian [27%], 8 White [73%]) were included, with diverse expertise in ethics, ophthalmology, translational medicine, biostatistics, and AI development. Key themes revealed several ethical challenges unique to clinical trials of AI. These themes included difficulties in measuring social value, establishing scientific validity, ensuring fair participant selection, evaluating risk-benefit ratios across various patient subgroups, and addressing the complexities inherent in the data use terms of informed consent. Conclusions and Relevance: This qualitative study identified practical ethical challenges that investigators need to consider and negotiate when conducting AI clinical trials, exemplified by the DR screening use-case. These considerations call for further guidance on where to focus empirical and normative ethical efforts to best support conduct clinical trials of AI and minimize unintended harm to trial participants.
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Inteligencia Artificial , Ensayos Clínicos como Asunto , Retinopatía Diabética , Humanos , Inteligencia Artificial/ética , Retinopatía Diabética/diagnóstico , Ensayos Clínicos como Asunto/ética , Femenino , Investigación Cualitativa , Proyectos de Investigación , Masculino , Estados UnidosRESUMEN
PURPOSE: To evaluate the findings and the correlation of optical coherence tomography angiography and pattern and flash electroretinography in diabetes mellitus without retinopathy. METHODS: Seventy-six eyes of 38 diabetic patients and age- and gender-matched control subjects were included in the study. The foveal avascular zone (FAZ), whole, foveal, parafoveal and perifoveal vascular densities of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillary plexus (CCP) layers were analyzed using optical coherence tomography angiography (OCTA). The amplitudes and implicit times of P50 and N95 waves of the pattern ERG (pERG) and the amplitudes and implicit times of the scotopic and photopic b-waves and oscillatory potentials (OP) of the flash ERG (fERG) tests were evaluated using the Metrovision brand monpack model device. RESULTS: The mean age of the patients was 59.7 ± 7.9 [range 43-79] years. Eighteen (47%) of the patients were female and 20 (53%) were male. The mean duration of diabetes was 7.45 ± 6.2 [range 1-20] years. No significant difference in FAZ area was found between study subjects and controls. Vascular density (VD) values of the superficial capillary plexus (SCP) layer were significantly lower (whole VD, 44.7 ± 3.3 vs. 46.6 ± 3.2%, p = 0.01, foveal VD 16.8 ± 6.4 vs. 24.9 ± 6.1%, p < 0.01, parafoveal VD 45.6 ± 4.5 vs. 47.1 ± 4.4%, p = 0.27 and perifoveal VD 45.5 ± 3.3 vs. 47.3 ± 3.1%, p = 0.01, respectively) in the diabetic group except the parafoveal area. VD measurements in deep and choriocapillary plexuses did not significantly differ between the groups (p > 0.05). ERG tests revealed significantly lower scotopic b-wave amplitudes (130.2 ± 39.3 µV vs.163.3 ± 47.8 µV, p < 0.01) and photopic b-wave amplitudes (83.2 ± 20.7 µV vs. 99.6 ± 29.4 µV, p < 0.01) in the diabetic patients. The implicit time of the photopic responses was significantly prolonged (28.9 ± 1.3 ms vs. 27.8 ± 2.1 ms, p = 0.01) in the patients. Oscillatory potentials in all components consisting of O1 to O4 and the sum of the OP potentials were lower in the diabetic group than the control subjects (p < 0.001). The P50 and N95 amplitudes and implicit times were comparable between the groups (p > 0.05). Correlation analysis showed a positive correlation between N95 amplitudes in pERG and the superficial vessel densities in OCTA (r = 0.26, p = 0.04). A negative correlation was found between photopic implicit times in fERG and the choriocapillary vessel densities (r=-0.27, p = 0.03). CONCLUSION: OCTA revealed decreased superficial vascular densities with the onset of the metabolic process of diabetes mellitus. As a result of these structural changes, lower scotopic and photopic amplitudes, decreased OP amplitudes, and prolonged implicit times in flash ERG were obtained.
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Electrorretinografía , Tomografía de Coherencia Óptica , Humanos , Electrorretinografía/métodos , Masculino , Tomografía de Coherencia Óptica/métodos , Femenino , Persona de Mediana Edad , Anciano , Adulto , Angiografía con Fluoresceína/métodos , Retinopatía Diabética/fisiopatología , Retinopatía Diabética/diagnóstico por imagen , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/fisiopatología , Estudios de Casos y Controles , Fóvea Central/diagnóstico por imagen , Fóvea Central/irrigación sanguínea , Fóvea Central/fisiopatología , Diabetes Mellitus/fisiopatología , Diabetes Mellitus/diagnóstico por imagen , Retina/diagnóstico por imagen , Retina/fisiopatologíaRESUMEN
Purpose: Long-term ramifications of the coronavirus disease 2019 pandemic on various care-seeking characteristics of patients with diabetic retinopathy remain unclear. This study aimed to identify risk factors for dropout from regular fundus examinations (RFEs) in patients with diabetic retinopathy in Japan. Methods: We extracted demographic and health checkup data (April 2018 to March 2021) from the JMDC database. Patients with diabetes identified using diagnosis-related and medication codes were included. The dropout and continuation groups included patients who discontinued and continued to undergo RFEs during the coronavirus disease 2019 pandemic, respectively. Results: The number of RFEs was significantly lower during the mild lockdown period (April and May 2020) than during the prepandemic period. Of the 14,845 patients with diabetes, 2333 (15.7%) dropped out of RFEs during the pandemic, whereas before the pandemic, of the 11,536 patients with diabetes, 1666 (14.4%) dropped out of RFEs (P = 0.004). Factors associated with dropout in the multivariate logistic regression analysis included younger age, male sex, high triglyceride levels, high γ-glutamyl transpeptidase levels, smoking habit, alcohol consumption, weight gain of more than 10 kg since the age of 20 years, and certain stages of lifestyle improvement. Factors associated with continuation included low body mass index and high glycosylated hemoglobin levels. Conclusions: Our findings can assist in identifying patients with diabetes at risk of dropout. Translational Relevance: These results have implications for public health and identifying patients with diabetes at risk of dropout. Education and tailored monitoring regimens could be pivotal role in fostering adherence.
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COVID-19 , Retinopatía Diabética , Humanos , COVID-19/epidemiología , Masculino , Retinopatía Diabética/epidemiología , Femenino , Japón/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , SARS-CoV-2 , Adulto , Factores de Riesgo , Pandemias , Atención Ambulatoria/estadística & datos numéricosRESUMEN
Introduction: Oxidative stress has been identified as a major contributor to the pathogenesis of DR, and many diagnostic and therapeutic strategies have been developed to target oxidative stress. Our aim was to understand the contribution of the country of origin of the publication, the institution, the authors, and the collaborative relationship between them. Methods: We performed a bibliometric analysis to summarize and explore the research hotspots and trends of oxidative stress in the DR. Results: We observe an upward trend in the number of posts on related topics from year to year. Expanding on this, Queens University Belfast is the most influential research institution. Current research hotspots and trends focus on the mechanism of autophagy and NLRP3 inflammasome's role in oxidative stress in DR. Discussion: We conducted a multi-dimensional analysis of the research status of oxidative stress in diabetic retinopathy through bibliometric analysis, and proposed possible future research trends and hotspots.
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Retinopatía Diabética , Estrés Oxidativo , Estrés Oxidativo/fisiología , Humanos , Retinopatía Diabética/metabolismo , Retinopatía Diabética/epidemiología , Bibliometría , Investigación Biomédica/tendenciasAsunto(s)
Retinopatía Diabética , Hipertensión , Presión Intraocular , Análisis de la Aleatorización Mendeliana , Humanos , Retinopatía Diabética/genética , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología , Hipertensión/genética , Hipertensión/epidemiología , Presión Intraocular/fisiologíaRESUMEN
Diabetic retinopathy is a common yet severe complication of diabetes mellitus and is the leading cause of blindness in middle-aged adults. After years of poorly managed hyperglycemia, complications begin as non-proliferative diabetic retinopathy but can then progress into the proliferative stage marked by neovascularization of the retina. Multiple pathologic mechanisms caused by chronic hyperglycemia damage the retinal vasculature leading to pericyte drop out and the progression of the disease. This review outlines the major pathways of pathogenesis in diabetic retinopathy, highlighting the protective role pericytes play in preserving the blood-retinal barrier. Given the loss of this cell line is a defining feature of the disease, ways in which to prevent pericyte dropout within retinal vasculature is discussed, targeting various pathogenesis pathways of diabetic retinopathy.
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Barrera Hematorretinal , Retinopatía Diabética , Pericitos , Retinopatía Diabética/patología , Retinopatía Diabética/metabolismo , Pericitos/metabolismo , Pericitos/patología , Humanos , Barrera Hematorretinal/metabolismo , Animales , Vasos Retinianos/patología , Vasos Retinianos/metabolismoRESUMEN
Secretogranin III (Scg3) is a diabetic retinopathy (DR)-restricted angiogenic factor identified in preclinical studies as a target for DR therapy. Previously, our group generated and characterized ML49.3, an anti-Scg3 monoclonal antibody (mAb) which we then converted into an EBP2 humanized antibody Fab fragment (hFab) with potential for clinical application. We also generated anti-Scg3 mT4 mAb and related EBP3 hFab. In this study, to identify the preferred hFab for DR therapy, we compared all four antibodies for binding, neutralizing and therapeutic activities in vitro and in vivo. Octet binding kinetics analyses revealed that ML49.3 mAb, EBP2 hFab, mT4 mAb and EBP3 hFab have Scg3-binding affinities of 35, 8.7, 0.859 and 0.116 nM, respectively. Both anti-Scg3 EBP2 and EBP3 hFabs significantly inhibited Scg3-induced proliferation and migration of human umbilical vein endothelial cells in vitro, and alleviated DR vascular leakage and choroidal neovascularization with high efficacy. Paired assays in DR mice revealed that intravitreally injected EBP3 hFab is 26.4% and 10.3% more effective than EBP2 hFab and aflibercept, respectively, for ameliorating DR leakage. In conclusion, this study confirms the markedly improved binding affinities of hFabs compared to mAbs and further identifies EBP3 hFab as the preferred antibody to develop for anti-Scg3 therapy.
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Inhibidores de la Angiogénesis , Anticuerpos Neutralizantes , Retinopatía Diabética , Células Endoteliales de la Vena Umbilical Humana , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/metabolismo , Retinopatía Diabética/inmunología , Retinopatía Diabética/patología , Humanos , Animales , Ratones , Anticuerpos Neutralizantes/farmacología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Ratones Endogámicos C57BL , Proteínas de Unión al ARN , Proteínas Adaptadoras Transductoras de SeñalesRESUMEN
Diabetic retinopathy is one of the leading causes of blindness around the world. This makes early diagnosis and treatment important in preventing vision loss in a large number of patients. Microaneurysms are the key hallmark of the early stage of the disease, non-proliferative diabetic retinopathy, and can be detected using OCT angiography quickly and non-invasively. Screening tools for non-proliferative diabetic retinopathy using OCT angiography thus have the potential to lead to improved outcomes in patients. We compared different configurations of ensembled U-nets to automatically segment microaneurysms from OCT angiography fundus projections. For this purpose, we created a new database to train and evaluate the U-nets, created by two expert graders in two stages of grading. We present the first U-net neural networks using ensembling for the detection of microaneurysms from OCT angiography en face images from the superficial and deep capillary plexuses in patients with non-proliferative diabetic retinopathy trained on a database labeled by two experts with repeats.
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Retinopatía Diabética , Microaneurisma , Tomografía de Coherencia Óptica , Retinopatía Diabética/diagnóstico por imagen , Humanos , Microaneurisma/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Redes Neurales de la Computación , Angiografía/métodos , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Angiografía con Fluoresceína/métodosRESUMEN
Background: Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes, and understanding its molecular mechanisms is crucial. Endoplasmic reticulum (ER) stress has been implicated in various diseases, including diabetic complications. This study aims to elucidate ER stress-related biomarkers in PDR, providing insights into the underlying molecular pathways. Methods: We analyzed two independent PDR datasets, GSE102485 and GSE60436. The GSE102485 dataset (22 PDR and 3 normal samples) was the primary dataset for comprehensive analyses, including differential expression, functional enrichment, PPI network construction, immune cell infiltration, and drug prediction. The GSE60436 dataset (6 PDR and 3 normal samples) was used for validation. In vitro experiments using human umbilical vein endothelial cells (HUVECs) in a high-glucose environment were conducted to validate key bioinformatics outcomes. Western blotting assessed protein levels of ER stress markers (TRAM1 and TXNIP). Results: Differential expression analysis identified 2451 genes, including 328 ER stress-related genes. Functional analysis revealed enrichment in ER stress-related processes and pathways. Hub genes (BCL2, CCL2, IL-1ß, TLR4, TNF, TP53) were identified, and immune infiltration analysis showed altered immune cell proportions. Validation in GSE60436 and in vitro confirmed ER stress gene dysregulation. Drug prediction suggested potential small molecules targeting ER stress markers. Conclusion: This study provides a comprehensive molecular characterization of ER stress in PDR, highlighting altered biological processes, immune changes, and potential therapeutic targets. The identified hub genes and small molecules offer avenues for further investigation and therapy development, enhancing understanding of PDR pathogenesis and aiding targeted intervention creation.
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Biología Computacional , Retinopatía Diabética , Estrés del Retículo Endoplásmico , Humanos , Estrés del Retículo Endoplásmico/genética , Retinopatía Diabética/genética , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Retinopatía Diabética/inmunología , Biología Computacional/métodos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Masculino , Femenino , Perfilación de la Expresión Génica , Biomarcadores/metabolismo , Persona de Mediana Edad , Mapas de Interacción de ProteínasRESUMEN
PURPOSE: To investigate the risk of visual impairment (VI) based on the presence or absence of four diseases: hypertension (HTN), diabetes mellitus (DM), glaucoma, and diabetic retinopathy (DR). METHODS: This retrospective population-based study included 1,000,000 randomly selected participants from the National Health Checkup Program database between 2015 and 2016. VI was defined as a presenting visual acuity ≤ 0.5 in the better eye. The participants were divided into 12 groups according to the presence or absence of disease. Adjusting for age and sex, the risk of VI in each disease group was analyzed and compared with the others. RESULTS: Among the 1,000,000 participants, 88,931 (8.89%) had VI. The odds ratios (ORs) of age, male sex, HTN, DM, glaucoma, and DR for VI were 1.06 (95% CI, 1.05-1.06), 0.52 (95% CI, 0.52-0.53), 1.11 (95% CI, 1.09-1.13), 1.07 (95% CI, 1.05-1.09), 0.92 (95% CI, 0.90-0.74), and 1.29 (95% CI, 1.25-1.34), respectively (all P < 0.001). The group with HTN, DM, glaucoma, and DR had the highest OR of 1.98 (P < 0.001) compared to the healthy group. HTN, DM, and DR were positively correlated with VI in all groups. Glaucoma was positively correlated in the group with DM and DR and in the group with HTN, DM, and DR (ORs 1.18, 1.11, all P < 0.05); however, it demonstrated a negative correlation in the other groups (ORs 0.85-0.93, all P < 0.05). CONCLUSION: HTN, DM, and DR, either alone or in combination, increase the risk of VI. Glaucoma also increases the risk when combined with DR; however, it has a negative correlation with VI in the absence of DR. Periodic ophthalmologic examinations for glaucoma, which primarily affects the peripheral visual field and not central visual acuity, might help prevent VI caused by other diseases.
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Comorbilidad , Retinopatía Diabética , Glaucoma , Hipertensión , Trastornos de la Visión , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Glaucoma/epidemiología , Glaucoma/complicaciones , Retinopatía Diabética/epidemiología , Trastornos de la Visión/epidemiología , Hipertensión/epidemiología , Hipertensión/complicaciones , Factores de Riesgo , Anciano , Adulto , Diabetes Mellitus/epidemiología , Agudeza VisualRESUMEN
BACKGROUND: To analyse and compare the grading of diabetic retinopathy (DR) severity level using standard 35° ETDRS 7-fields photography and CLARUS™ 500 ultra-widefield imaging system. METHODS: A cross-sectional analysis of retinal images of patients with type 2 diabetes (n = 160 eyes) was performed for this study. All patients underwent 7-fields colour fundus photography (CFP) at 35° on a standard Topcon TRC-50DX® camera, and ultra-widefield (UWF) imaging at 200° on a CLARUS™ 500 (ZEISS, Dublin, CA, USA) by an automatic montage of two 133° images (nasal and temporal). 35° 7-fields photographs were graded by two graders, according to the Early Treatment Diabetic Retinopathy Study (ETDRS). For CLARUS UWF images, a prototype 7-fields grid was applied using the CLARUS review software, and the same ETDRS grading procedures were performed inside that area only. Grading of DR severity level was compared between these two methods to evaluate the agreement between both imaging techniques. RESULTS: Images of 160 eyes from 83 diabetic patients were considered for analysis. According to the 35° ETDRS 7-fields images, 22 eyes were evaluated as DR severity level 10-20, 64 eyes were evaluated as DR level 35, 41 eyes level 43, 21 eyes level 47, 7 eyes level 53, and 5 eyes level 61. The same DR severity level was achieved with CLARUS 500 UWF images in 92 eyes (57%), showing a perfect agreement (k > 0.80) with the 7-fields 35° technique. Fifty-seven eyes (36%) showed a higher DR level with CLARUS UWF images, mostly due to a better visualization of haemorrhages and a higher detection rate of intraretinal microvascular abnormalities (IRMA). Only 11 eyes (7%) showed a lower severity level with the CLARUS UWF system, due to the presence of artifacts or media opacities that precluded the correct evaluation of DR lesions. CONCLUSIONS: UWF CLARUS 500 device showed nearly perfect agreement with standard 35° 7-fields images in all ETDRS severity levels. Moreover, CLARUS images showed an increased ability to detect haemorrhages and IRMA helping with finer evaluation of lesions, thus demonstrating that a UWF photograph can be used to grade ETDRS severity level with a better visualization than the standard 7-fields images. TRIAL REGISTRATION: Approved by the AIBILI - Association for Innovation and Biomedical Research on Light and Image Ethics Committee for Health with number CEC/009/17- EYEMARKER.
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Fotograbar , Índice de Severidad de la Enfermedad , Humanos , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/diagnóstico por imagen , Estudios Transversales , Femenino , Masculino , Persona de Mediana Edad , Fotograbar/métodos , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Fondo de Ojo , Técnicas de Diagnóstico Oftalmológico , Adulto , Reproducibilidad de los ResultadosRESUMEN
This study was intended to investigate the macular vascular and photoreceptor changes for diabetic macular edema (DME) at the early stage. A total of 255 eyes of 134 diabetes mellitus patients were enrolled and underwent an ophthalmological and systemic evaluation in this cross-sectional study. Early DME was characterized by central subfoveal thickness (CST) value between 250 and 325 µm, intact ellipsoid zone, and an external limiting membrane. While non-DME was characterized by CST < 250 µm with normal retinal morphology and structure. Foveal avascular zone (FAZ) area ≤ 0.3 mm2 (P < 0.001, OR = 0.41, 95% CI 0.26-0.67 in the multivariate analysis) and HbA1c level ≤ 8% (P = 0.005, OR = 0.37, 95% CI 0.19-0.74 in multivariate analysis) were significantly associated with a higher risk of early DME. Meanwhile, no significant differences exist in cone parameters between non-DME and early DME eyes. Compared with non-DME eyes, vessel diameter, vessel wall thickness, wall-to-lumen ratio, the cross-sectional area of the vascular wall in the upper side were significantly decreased in the early DME eyes (P = 0.001, P < 0.001, P = 0.005, P = 0.003 respectively). This study suggested a vasospasm or vasoconstriction with limited further photoreceptor impairment at the early stage of DME formation. CST ≥ 250 µm and FAZ ≤ 0.3 mm2 may be the indicator for early DME detection.
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Retinopatía Diabética , Edema Macular , Vasos Retinianos , Humanos , Edema Macular/patología , Edema Macular/etiología , Edema Macular/diagnóstico por imagen , Masculino , Femenino , Retinopatía Diabética/patología , Retinopatía Diabética/diagnóstico por imagen , Persona de Mediana Edad , Estudios Transversales , Anciano , Vasos Retinianos/patología , Vasos Retinianos/diagnóstico por imagen , Mácula Lútea/patología , Mácula Lútea/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Fóvea Central/patología , Fóvea Central/diagnóstico por imagenRESUMEN
Diabetic retinopathy (DR) is a specific microvascular problem of diabetes, which is mainly caused by hyperglycemia and may lead to rapid vision loss. Dietary polyphenols have been reported to decrease the risk of DR. Apocynum venetum L. leaves are rich in polyphenolic compounds and are popular worldwide for their health benefits as a national tea drink. Building on previous findings of antioxidant activity and aldose reductase inhibition of A. venetum, this study investigated the chemical composition of polyphenol-rich extract of A. venetum leaves (AVL) and its protective mechanism on ARPE-19 cells in hyperglycemia. Ninety-three compounds were identified from AVL by LC-MS/MS, including sixty-eight flavonoids, twenty-one organic acids, and four coumarins. AVL regulated the polyol pathway by decreasing the expression of aldose reductase and the content of sorbitol, enhancing the Na+K+-ATPase activity, and weakening intracellular oxidative stress effectively; it also could regulate the expression of autophagy-related proteins via the AMPK/mTOR/ULK1 signaling pathway to maintain intracellular homeostasis. AVL could restore the polyol pathway, inhibit oxidative stress, and maintain intracellular autophagy to protect cellular morphology and improve DR. The study reveals the phytochemical composition and protective mechanisms of AVL against DR, which could be developed as a functional food and/or candidate pharmaceutical, aiming for retina protection in diabetic retinopathy.
Asunto(s)
Apocynum , Autofagia , Glucosa , Estrés Oxidativo , Extractos Vegetales , Hojas de la Planta , Polifenoles , Epitelio Pigmentado de la Retina , Humanos , Extractos Vegetales/farmacología , Polifenoles/farmacología , Polifenoles/análisis , Hojas de la Planta/química , Autofagia/efectos de los fármacos , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/metabolismo , Glucosa/metabolismo , Glucosa/efectos adversos , Apocynum/química , Estrés Oxidativo/efectos de los fármacos , Polímeros , Línea Celular , Retinopatía Diabética/prevención & control , Retinopatía Diabética/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Transducción de Señal/efectos de los fármacos , Antioxidantes/farmacología , Aldehído Reductasa/metabolismoRESUMEN
Diabetic retinopathy (DR), a leading cause of blindness in diabetic patients, necessitates the precise segmentation of lesions for the effective grading of lesions. DR multi-lesion segmentation faces the main concerns as follows. On the one hand, retinal lesions vary in location, shape, and size. On the other hand, the currently available multi-lesion region segmentation models are insufficient in their extraction of minute features and are prone to overlooking microaneurysms. To solve the above problems, we propose a novel deep learning method: the Multi-Scale Spatial Attention Gate (MSAG) mechanism network. The model inputs images of varying scales in order to extract a range of semantic information. Our innovative Spatial Attention Gate merges low-level spatial details with high-level semantic content, assigning hierarchical attention weights for accurate segmentation. The incorporation of the modified spatial attention gate in the inference stage enhances precision by combining prediction scales hierarchically, thereby improving segmentation accuracy without increasing the associated training costs. We conduct the experiments on the public datasets IDRiD and DDR, and the experimental results show that the proposed method achieves better performance than other methods.
Asunto(s)
Aprendizaje Profundo , Retinopatía Diabética , Retinopatía Diabética/patología , Humanos , Retina/patología , Procesamiento de Imagen Asistido por Computador/métodos , Atención/fisiología , AlgoritmosRESUMEN
PURPOSE: To determine the association of gut microbiome diversity and sight-threatening diabetic retinopathy (STDR) amongst patients with pre-existing diabetes. METHODS: A cross-sectional study was performed, wherein 54 participants selected in total were placed into cases cohort if diagnosed with STDR and those without STDR but had a diagnosis of diabetes mellitus of at least 10-year duration were taken as controls. Statistical analysis comparing the gut microbial alpha diversity between cases and control groups as well as patients differentiated based on previously hypothesized Bacteroidetes/Firmicutes(B/F) ratio with an optimal cut-off 1.05 to identify patients with STDR were performed. RESULTS: Comparing gut microbial alpha diversity did not show any difference between cases and control groups. However, statistically significant difference was noted amongst patients with B/F ratio ≥1.05 when compared to B/F ratio < 1.05; ACE index [Cut-off < 1.05:773.83 ± 362.73; Cut-off > 1.05:728.03 ± 227.37; p-0.016]; Chao1index [Cut-off < 1.05:773.63 ± 361.88; Cut-off > 1.05:728.13 ± 227.58; p-0.016]; Simpson index [Cut-off < 1.05:0.998 ± 0.001; Cut-off > 1.05:0.997 ± 0.001; p-0.006]; Shannon index [Cut-off < 1.05:6.37 ± 0.49; Cut-off > 1.05:6.10 ± 0.43; p-0.003]. Sub-group analysis showed that cases with B/F ratio ≥ 1.05, divided into proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME), showed decreased diversity compared to controls (B/F ratio < 1.05). For PDR, all four diversity indices significantly decreased (p < 0.05). However, for CSME, only Shannon and Simpson indices showed significant decrease in diversity (p < 0.05). CONCLUSIONS: Based on clinical diagnosis, decreasing gut microbial diversity was observed among patients with STDR, although not statistically significant. When utilizing B/F ratio, the decreasing gut microbial diversity in STDR patients seems to be associated due to species richness and evenness in PDR when compared to decreasing species richness in CSME.
Asunto(s)
Retinopatía Diabética , Microbioma Gastrointestinal , Humanos , Retinopatía Diabética/microbiología , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Adulto , Bacteroidetes/aislamiento & purificación , Bacteroidetes/genética , Bacteroidetes/clasificación , Anciano , Estudios de Casos y Controles , Biodiversidad , Firmicutes/aislamiento & purificación , Firmicutes/clasificación , Firmicutes/genéticaRESUMEN
BACKGROUND: Diabetes mellitus has emerged as a pressing global concern, with a notable increase in recent years. Despite advancements in treatment, existing medications struggle to halt the progression of diabetes and its associated complications. Increasing evidence underscores inflammation as a significant driver in the onset of diabetes mellitus. Therefore, perspectives on new therapies must consider shifting focus from metabolic stress to inflammation. High mobility group box (HMGB-1), a nuclear protein regulating gene expression, gained attention as an endogenous danger signal capable of sparking inflammatory responses upon release into the extracellular environment in the late 1990s. PURPOSE: Given the parallels between inflammatory responses and type 2 diabetes (T2D) development, this review paper explores HMGB-1's potential involvement in onset and progression of diabetes complications. Specifically, we will review and update the understanding of HMGB-1 and its inflammatory pathways in insulin resistance, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy. CONCLUSIONS: HMGB-1 and its receptors i.e. receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) present promising targets for antidiabetic interventions. Ongoing and future projects in this realm hold promise for innovative approaches targeting HMGB-1-mediated inflammation to ameliorate diabetes and its complications.
Asunto(s)
Proteína HMGB1 , Hipoglucemiantes , Receptor para Productos Finales de Glicación Avanzada , Transducción de Señal , Humanos , Proteína HMGB1/metabolismo , Proteína HMGB1/antagonistas & inhibidores , Animales , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Receptor para Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Hipoglucemiantes/uso terapéutico , Mediadores de Inflamación/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Antiinflamatorios/uso terapéutico , Terapia Molecular Dirigida , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Resistencia a la Insulina , Receptores Toll-Like/metabolismo , Retinopatía Diabética/metabolismo , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/etiología , Retinopatía Diabética/prevención & control , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/tratamiento farmacológico , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/tratamiento farmacológicoRESUMEN
OBJECTIVE: This study seeks to explain the relationship between systemic conditions and hard exudate formations in diabetic macular edema patients. Besides, the study aimed to quantitatively examine changes in the area, location, and impact on visual function of hard exudates following intravitreal dexamethasone implant injections. METHODS: A retrospective analysis was conducted, including 40 patients (40 eyes) diagnosed with non-proliferative diabetic retinopathy and concurrent macular edema between January 1, 2022, and January 1, 2024. Preoperative evaluations included glycated hemoglobin, lipid profile, and renal function examinations. Based on the location of HE, patients were divided into two groups: Group A, with HE in 1 mm of the central fovea, and Group B, with HE outside 1 mm of the central fovea. Selected eyes were subject to pre- and postoperative examinations, including best-corrected visual acuity (BCVA), intraocular pressure, slit-lamp biomicroscopy, scanning laser ophthalmoscopy (SLO), optical coherence tomography, and multifocal electroretinography. Following screening and examination, patients received an immediate intravitreal injection of the DEX implant, with an injection administered at the four-month mark. Hard exudate (HE) areas were measured utilizing SLO fundus imaging. RESULTS: Total cholesterol, low-density lipoprotein, and triglyceride levels were found to be positively correlated with the presence of HE. Following surgical intervention, all patients demonstrated an improvement in BCVA. The mean BCVA increased from a preoperative measurement of 0.79 ± 0.04 to 0.39 ± 0.02 at the 6 month follow-up, indicating a statistically significant difference (p < 0.001). The baseline HE area for the entire patient cohort was 2.28 ± 0.22. One month post-operation, the HE area exhibited a slight increase to 2.27 ± 0.22. However, by the 6 month follow-up, the HE area had significantly decreased to 0.8 ± 0.87, representing a 35.09% reduction from the baseline measurement (p < 0.001). It is worth noting that Patient P1 did not exhibit a statistically significant difference between preoperative and six-month postoperative HE area (p = 0.032). Preoperative BCVA measurements for Group A and Group B were 0.81 ± 0.03 and 0.77 ± 0.03, respectively, with no statistically significant intergroup difference (p = 0.333). The baseline HE area for Group A was 2.61 ± 0.16, which decreased to 0.38 ± 0.20 at the six-month follow-up, representing a 14.60% reduction from the baseline total area. For Group B, the baseline HE area was measured at 1.95 ± 0.09, then decreasing to 1.21 ± 0.13 at the six-month follow-up, indicating a 62.05% reduction from the baseline total area. A statistically significant difference in the postoperative 6 month HE area was observed between Group A and Group B (p < 0.001). In Group A, the reduction in HE area (initial HE area-final HE area) was positively correlated with the improvement in P1 (initial P1-final P1) (r = 0.610, p = 0.004). In Group B, a similar positive correlation was found (initial HE area-final HE area with initial P1-final P1) (r = 0.488, p = 0.029). In Group B, the reduction in HE area (initial HE area-final HE area) correlated positively with the improvement in BCVA (initial BCVA-final BCVA) (r = 0.615, p = 0.004). Additionally, in Group B, the reduction in HE area (initial HE area-final HE area) was positively correlated with the improvement in CMT (initial CMT-final CMT) (r = -0.725, p< 0.001). Aggravated cataracts were observed in thirteen eyes during a follow-up examination 6 months later. CONCLUSION: HE formation is associated with lipid levels. Dexamethasone implants demonstrate effectiveness in reducing HE areas in the short term, reducing macular edema, improving retinal structure, and enhancing visual function. The incidence of postoperative complications such as cataracts and glaucoma remains low.