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BACKGROUND: Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood. METHODS: This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period. RESULTS: We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001). CONCLUSIONS: This study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops.
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Neoplasias , Humanos , Feminino , Masculino , Neoplasias/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Adulto , Estudos Longitudinais , Incidência , Diabetes Mellitus/epidemiologia , Taiwan/epidemiologia , Fatores de Risco , Adulto Jovem , Complicações do Diabetes/epidemiologia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: To comprehend the complexities of pathophysiological mechanisms and molecular events that contribute to proliferative diabetic retinopathy (PDR) and evaluate the diagnostic value of aqueous humor (AH) in monitoring the onset of PDR. METHODS: A cohort containing 16 PDR and 10 cataract patients and another validation cohort containing 8 PDR and 4 cataract patients were studied. AH was collected and subjected to proteomics analyses. Bioinformatics analysis and a machine learning-based pipeline called inference of biomolecular combinations with minimal bias were used to explore the functional relevance, hub proteins, and biomarkers. RESULTS: Deep profiling of AH proteomes revealed several insights. First, the combination of SIAE, SEMA7A, GNS, and IGKV3D-15 and the combination of ATP6AP1, SPARCL1, and SERPINA7 could serve as surrogate protein biomarkers for monitoring PDR progression. Second, ALB, FN1, ACTB, SERPINA1, C3, and VTN acted as hub proteins in the profiling of AH proteomes. SERPINA1 was the protein with the highest correlation coefficient not only for BCVA but also for the duration of diabetes. Third, "Complement and coagulation cascades" was an important pathway for PDR development. CONCLUSIONS: AH proteomics provides stable and accurate biomarkers for early warning and diagnosis of PDR. This study provides a deep understanding of the molecular mechanisms of PDR and a rich resource for optimizing PDR management.
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Vasohibin-2 (VASH2) is confirmed to be associated with angiogenesis. To investigate the vitreous levels of VASH2 and how VASH2 induces angiogenesis in proliferative diabetic retinopathy (PDR), a total of 120 eyes were enrolled in this prospective and randomized controlled study and the vitreous level of VASH2 was quantified by Luminex liquid suspension chip. Vector systems were applied in human retinal microvascular endothelial cells (HRMECs) for VASH2 gene overexpression, along with interfering lentiviral vectors (VASH2-shRNA) for VASH2 gene silencing. Cell migration, autophagic flux, as well as the expression of α-tubulin, detyrosinated âº-tubulin, LC3 II/LC3 I, P62 were detected under normal, VASH2 overexpression, or interference conditions. The level of VASH2 in PDR patients was significantly higher (218.61 ± 30.14 pg/ml) than that in ERM/MH patients (80.78 ± 2.05 pg/ml) (P = 0.001). The migration ability of HRMECs was significantly increased in VASH2 overexpression group, while in the interfering group, the migration ability decreased. VASH2 increased the detyrosination of âº-tubulin. The high fluorescence intensity of autophagic flux showed an activation of autophagy in VASH2 overexpression group, which was also confirmed by the increase of LC3 II/LC3 I ratio and the decrease of P62. Collectively, the present study shows in PDR, vitreous level of VASH2 is higher. VASH2 promotes neovascularization by inducing autophagy, suggesting VASH2 could be a new anti-angiogenic drug target for PDR.
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Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Células Endoteliais/metabolismo , Tubulina (Proteína)/metabolismo , Estudos Prospectivos , Neovascularização Patológica/metabolismo , Diabetes Mellitus/metabolismo , Proteínas Angiogênicas/genéticaRESUMO
Diabetic retinopathy (DR) is an eye disease that causes blindness and vision loss in diabetic. Risk factors for DR include high blood glucose levels and some environmental factors. The pathogenesis is based on inflammation caused by interferon and other nuclear proteins. This review article provides an overview of DR and discusses the role of nuclear proteins in the pathogenesis of the disease. Some core proteins such as MAPK, transcription co-factors, transcription co-activators, and others are part of this review. In addition, some current advanced treatment resulting from the role of nuclear proteins will be analyzes, including epigenetic modifications, the use of methylation, acetylation, and histone modifications. Stem cell technology and the use of nanobiotechnology are proposed as promising approaches for a more effective treatment of DR.
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Retinopatia Diabética , Proteínas Nucleares , Retinopatia Diabética/metabolismo , Humanos , Proteínas Nucleares/metabolismo , Animais , Epigênese GenéticaRESUMO
PURPOSE: To explore the association between widefield swept-source optical coherence tomography angiography (WF SS-OCTA) metrics, including nonperfusion area (NPA) and neovascularization (NV), and presence of neovascular glaucoma (NVG) in patients with proliferative diabetic retinopathy (PDR). METHODS: A prospective, cross-sectional study was conducted from November 2018 to February 2020. A total of 85 eyes of 60 PDR patients without NVG and 9 eyes of 8 PDR patients with NVG were included. Retinal ischemic parameters (NPA; ischemia index [NPA/total retinal area]) and NV features (NV number; NV area; NV vessel density) were evaluated. Foveal avascular zone (FAZ), macular thickness/volume, and choroidal thickness/volume were obtained using the Zeiss ARI Network. WF SS-OCTA retinal and choroidal metrics, systemic, and ocular parameters were screened using Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression for variable selection. Firth's bias-reduced logistic regression (outcome: presence of NVG) was subsequently used to identify parameters associated with NVG. RESULTS: After LASSO variable selection, 8 variables were significantly associated with the presence of NVG: DM duration (years), insulin (yes/no), best-corrected visual acuity (BCVA) (logMAR), IOP, ischemia index, skeletonized vessel density, macular thickness (inner inferior, outer temporal regions). Firth's bias-reduced logistic regression showed ischemia index (odds ratio [OR]=13.2, 95% confidence interval [CI]:5.3-30.7, P<0.001) and BCVA (OR=5.8, 95%CI:1.2-28.8, P<0.05) were associated with the presence of NVG. NV metrics, FAZ, and choroidal parameters were not related to NVG. CONCLUSIONS: Retinal ischemia but not NV was associated with the presence of NVG in patients with PDR using WF SS-OCTA. Larger, longitudinal studies are needed to validate imaging biomarkers associated with diabetic NVG.
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Diabetes Mellitus , Retinopatia Diabética , Glaucoma Neovascular , Humanos , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Vasos Retinianos , Angiofluoresceinografia/métodos , Glaucoma Neovascular/diagnóstico , Glaucoma Neovascular/etiologia , Tomografia de Coerência Óptica/métodos , Estudos Transversais , Estudos Prospectivos , Isquemia , Neovascularização PatológicaRESUMO
PURPOSE: Comparing characteristics and outcomes of patients with bilateral proliferative diabetic retinopathy (PDR) undergoing concurrent and sequential vitrectomy. METHODS: Patients having bilateral vitrectomy were classified into concurrent (requiring bilateral surgery simultaneously) and sequential (indicating vitrectomy in one eye later) groups. Clinical characteristics and outcomes were compared, and correlation between the first and second-operated eyes was analyzed. RESULTS: One hundred eight and 126 eyes were in the concurrent and sequential groups, respectively. The sequential group was older (50 vs. 45 years, P = 0.017), had less retinal detachment (54 vs. 77%, P < 0.001), and better visual outcomes (0.79 vs. 1.30, P = 0.021), especially the second-operated eyes. The concurrent group had weaker correlations of disease severity (phi coefficient: 0.36 vs. 0.61) and post-operative visual acuity (r: 0.12 vs. 0.34) between the first- and second-operated eyes than the sequential group. Prior intravitreal injection of anti-vascular endothelial growth factor (odds ratio [OR] 0.37, 95% confidence interval [CI] 0.15-0.86, P = 0.025) predicted better outcomes, while post-operative neovascular glaucoma predicted worse outcomes (OR 6.5, 95% CI 1.7-27.9, P = 0.008). CONCLUSIONS: PDR patients requiring surgery concurrently were younger and had more severe diseases and worse outcomes. However, poor outcomes in the first eye did not predict similar outcomes in the second eye.
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Retinopatia Diabética , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Retinopatia Diabética/cirurgia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/complicações , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Retrospectivos , Resultado do Tratamento , Seguimentos , Idoso , AdultoRESUMO
PURPOSE: The purpose of this study was to assess whether diabetic NV is perfused by the arterial or the venous circulation. METHODS: This is a retrospective, consecutive case series evaluating patients with proliferative diabetic retinopathy (PDR) imaged with ultrawide-field (UWF) fluorescein angiography (FA). Areas of neovascularization elsewhere (NVE) and neovascularization of the disc (NVD) were assessed. Perfusion was defined as arterial, arteriovenous, or venous if the area of diabetic neovascularization (NV) began to hyperfluoresce either prior, during, or after laminar venous flow, respectively. RESULTS: A total of 180 eyes from 176 patients with 928 NV were identified (830 NVE, 98 NVD). Of those, 5.1% of NVE were classified as arterial and 58.2% of NVD were classified as arterial. The remaining NV were classified as arteriovenous except for a small subset (6.1%) which were indeterminate. None of the NV were classified as venous. Noteworthy examples demonstrated NV that nearly fully perfused prior to any detectable fluorescence within nearby veins as well as clear shunting of blood from a feeding artery to a draining vein. CONCLUSIONS: UWF FA images suggest that some NV is perfused by retinal arteries. This may be useful in devising strategies for early detection and treatment of NV precursors. KEY MESSAGES: What is known ⢠Diabetic retinal neovascularization has long been thought to be perfused by the retinal venous circulation. ⢠Vascular endothelial growth factor has been shown to play key roles in both angiogenesis and arteriogenesis. What is new ⢠Ultrawide-field fluorescein angiography demonstrates that at least some diabetic neovascularization is perfused by the retinal arterial circulation. ⢠This supports the hypothesis that diabetic neovascularization may arise from arterially-perfused intraretinal microvascular abnormalities in the capillary bed.
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PURPOSE: To evaluate whether sodium-glucose co-transporter 2 (SGLT2) inhibitors affect progression of non-proliferative diabetic retinopathy (NPDR) compared to standard of care. METHODS: A retrospective cohort study compared subjects enrolled in a commercial and Medicare Advantage medical claims database who filled a prescription for a SGLT2 inhibitor between 2013 and 2020 to unexposed controls, matched up to a 1:3 ratio. Patients were excluded if they were enrolled for less than 2 years in the plan, had no prior ophthalmologic exam, had no diagnosis of NPDR, had a diagnosis of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), had received treatment for vision-threatening diabetic retinopathy (VTDR), or were younger than 18 years. To balance covariates of interest between the cohorts, an inverse probability treatment weighting (IPTW) propensity score for SGLT2 inhibitor exposure was used. Multivariate Cox proportional hazard regression modeling was employed to assess the hazard ratio (HR) for VTDR, PDR, or DME relative to SGLT2 exposure. RESULTS: A total of 6065 patients who initiated an SGLT2 inhibitor were matched to 12,890 controls. There were 734 (12%), 657 (10.8%), and 72 (1.18%) cases of VTDR, DME, and PDR, respectively, in the SGLT2 inhibitor cohort. Conversely, there were 1479 (11.4%), 1331 (10.3%), and 128 (0.99%) cases of VTDR, DME, and PDR, respectively, among controls. After IPTW, Cox regression analysis showed no difference in hazard for VTDR, PDR, or DME in the SGLT2 inhibitor-exposed cohort relative to the unexposed group [HR = 1.04, 95% CI 0.94 to 1.15 for VTDR; HR = 1.03, 95% CI 0.93 to 1.14 for DME; HR = 1.22, 95% CI 0.89 to 1.67 for PDR]. CONCLUSION: Exposure to SGLT2 inhibitor therapy was not associated with progression of NPDR compared to patients receiving other diabetic therapies.
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Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Inibidores do Transportador 2 de Sódio-Glicose , Estados Unidos/epidemiologia , Humanos , Idoso , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Estudos Retrospectivos , Transportador 2 de Glucose-Sódio , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , MedicareRESUMO
PURPOSE: To investigate the changes in aqueous humor (AH) protein profiles before and after intravitreal aflibercept (IVA) treatment in patients with proliferative diabetic retinopathy (PDR). METHODS: 5 PDR patients provided 10 samples of AH before and after IVA treatment (pre-group vs. post-group). Proteins were identified using liquid chromatography-tandem mass spectrometry. Then, bioinformatics was employed to investigate the functional significance of differentially expressed proteins (DEPs) and hub proteins. RESULTS: A total of 16 DEPs were identified, consisting of 8 downregulated proteins and 8 upregulated proteins. Bioinformatics analysis indicated that the most significantly enriched biological process was "blood coagulation, intrinsic pathway." The most significantly enriched signaling pathway was "complement and coagulation cascades." HBB, HPX, VEGFA, and CA1 were identified as hub proteins for IVA treatment. CONCLUSIONS: Together with the downregulation of the intravitreal vascular endothelial growth factor level, IVA may also change the AH protein composition in PDR patients, with DEPs involved in the blood coagulation, intrinsic pathway, complement, and coagulation cascades. IVA treatment may protect against PDR by regulating HBB, HPX, VEGFA, and CA1 expression.
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Diabetes Mellitus , Retinopatia Diabética , Proteínas Recombinantes de Fusão , Humanos , Humor Aquoso , Retinopatia Diabética/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêuticoRESUMO
BACKGROUND: This study evaluated impact of anti-vascular endothelial growth factor (VEGF) treatment on proliferative diabetic retinopathy (PDR) development among patients with non-proliferative diabetic retinopathy (NPDR) in US real-world clinical practice. METHODS: This was a retrospective analysis of electronic medical records (Vestrum Health; January 2013 to June 2019) of eyes with baseline NPDR, without DME, and naïve to anti-VEGF treatment at index DR diagnosis. Eyes that received anti-VEGF and/or laser treatment over the course of study before development of PDR constituted the treated cohort while the remaining including those treated with laser constituted the anti-VEGF naïve cohort. Survival analysis via Kaplan-Meier method evaluated time to DME and PDR development by baseline NPDR severity, with anti-VEGF treatment as censoring variable. Baseline factors affecting PDR development were analyzed using Cox multivariable regression, censoring for anti-VEGF treatment. RESULTS: Among anti-VEGF-naive eyes, cumulative incidence of DME in eyes with mild (n = 70,050), moderate (n = 39,116), and severe NPDR (n = 10,692) at baseline was 27.1%, 51.2%, and 60.6%. Multivariable regression analysis identified baseline NPDR severity as the most significant predictor of PDR development over 48 months (hazard ratio [HR] [95% confidence interval {CI}] of 2.69 (2.65-2.72) for moderate vs mild NPDR and 6.51 (6.47-6.55) for severe vs mild NPDR). Cumulative incidence (95% CI) of PDR was 7.9% (7.4%-8.3%), 20.9%, (20.0%-21.7%) and 46.8% (44.4%-49.2%) over 48 months in eyes with mild, moderate, and severe NPDR at baseline, respectively. Among treated eyes with baseline severe NPDR, cumulative incidence of PDR at 48 months was 50.1% in eyes treated with laser (n = 546; HR [95% CI] vs no treatment: 0.8 [0.7-1.0]), 27.4% in eyes treated with anti-VEGF (n = 923; HR [95% CI]: 0.4 [0.4-0.5]), and 25.6% in eyes treated with anti-VEGF plus laser (n = 293; HR [95% CI]: 0.5 [0.4-0.7]) compared with 49.9% in eyes with no treatment (n = 8930). CONCLUSIONS: DME and PDR development rates increased with increasing baseline NPDR severity. Approximately half of anti-VEGFânaive eyes with severe NPDR progressed to PDR within 4 years in US clinical practice. The progression rate from severe NPDR to PDR was approximately halved with anti-VEGF versus no treatment.
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Inibidores da Angiogênese , Retinopatia Diabética , Injeções Intravítreas , Fator A de Crescimento do Endotélio Vascular , Humanos , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/diagnóstico , Estudos Retrospectivos , Feminino , Masculino , Inibidores da Angiogênese/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Pessoa de Meia-Idade , Idoso , Ranibizumab/uso terapêutico , Ranibizumab/administração & dosagem , Acuidade Visual/fisiologia , Bevacizumab/uso terapêutico , Seguimentos , Adulto , IncidênciaRESUMO
PURPOSE: To investigate the effectiveness of anti-vascular endothelial growth factor (VEGF) therapy on post-vitrectomy macular edema (PVME) and determine the risk factors for PVME recovery. METHODS: This retrospective study included 179 eyes of 179 patients who underwent pars plana vitrectomy for proliferative diabetic retinopathy and developed PVME within 3 months after surgery. Eyes were grouped according to postoperative anti-VEGF treatment. RESULTS: Central retinal thickness (CRT) decreased significantly from baseline to 3-month follow-up in groups with (509.9 ± 157.2 µm vs. 401.2 ± 172.1 µm, P < 0.001) or without (406.1 ± 96.1 µm vs. 355.1 ± 126.0 µm, P = 0.008) postoperative anti-VEGF treatment. Best-corrected visual acuity (BCVA) did not differ between the two groups during follow-up. In the group not receiving anti-VEGF therapy, BCVA was significantly improved at 1, 2, and 3 months (P = 0.007, P < 0.001, and P < 0.001, respectively), while in the anti-VEGF group, BCVA was significantly improved at 1 and 3 months (P = 0.03 and P < 0.001). A thicker baseline CRT (ß = 0.44; 95% confidence interval, 0.26-0.61; P < 0.001) was significantly associated with decreasing CRT. CONCLUSION: PVME tends to spontaneously resolve in the early postoperative period. The effect of anti-VEGF therapy in the first 3 months after diagnosis appears to be limited.
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Inibidores da Angiogênese , Retinopatia Diabética , Edema Macular , Fator A de Crescimento do Endotélio Vascular , Vitrectomia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/cirurgia , Seguimentos , Injeções Intravítreas , Edema Macular/etiologia , Edema Macular/tratamento farmacológico , Edema Macular/diagnóstico , Complicações Pós-Operatórias , Ranibizumab/administração & dosagem , Ranibizumab/uso terapêutico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual , Vitrectomia/métodosRESUMO
BACKGROUND: Clinical evidence suggests an association between phosphate concentrations in aqueous humor and the risk of intraocular lens (IOL) calcification. To test this hypothesis the influence of different phosphate concentrations on IOL calcification was evaluated in an in vitro electrophoresis model. METHODS: 20 IOLs of two hydrophilic IOL models (CT Spheris 204, Zeiss; Lentis L-313, Oculentis) and one hydrophobic control IOL model (Clareon CNA0T0, Alcon) were exposed to physiologic and elevated phosphate concentrations, similar to diabetic aqueous humor. IOL calcification was analyzed by alizarin red staining, von Kossa staining, scanning electron microscopy, energy dispersive x-ray spectroscopy and transmission electron microscopy with electron diffraction. RESULTS: Higher phosphate concentrations were associated with IOL calcification. Analyses of IOL surfaces and cross-sections documented calcification in no CT Spheris and 4 Lentis IOLs following exposure to 10 mM Na2HPO4, compared with 7 and 11 positive analyses following exposure to 14 mM Na2HPO4, respectively. Furthermore, a clear association between IOL calcification and the duration of electrophoresis was demonstrated, confirming increased phosphate concentrations and duration of exposure as risk factors of IOL calcification. CONCLUSIONS: Findings suggest that higher phosphate concentrations in aqueous humor, as seen in diabetic patients, contribute to an increased IOL calcification risk, potentially explaining clinical observations showing an increased risk of IOL calcification in patients with diabetes.
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Humor Aquoso , Calcinose , Lentes Intraoculares , Fosfatos , Humanos , Humor Aquoso/metabolismo , Calcinose/metabolismo , Fosfatos/metabolismo , Microscopia Eletrônica de Varredura , Espectrometria por Raios X , Microscopia Eletrônica de Transmissão , Fatores de RiscoRESUMO
BACKGROUND: We aimed to evaluate microaneurysms (MAs) after treatment with anti-vascular endothelial growth factor (anti-VEGF) therapy to understand causes of chronic edema and anti-VEGF resistance. METHODS: Patients with non-proliferative diabetic retinopathy, with or without macular edema were recruited. Optical coherence tomography angiography (OCTA) MAs-related parameters were observed, including the maximum diameter of overall dimensions, material presence, and flow signal within the lumen. OCTA parameters also included central macular thickness (CMT), foveal avascular zone, superficial and deep capillary plexuses, and non-flow area measurements on the superficial retinal slab. RESULTS: Overall, 48 eyes from 43 patients were evaluated. CMT differed significantly between the diabetic macular edema (DME ) and non-DME (NDME) groups at 1st, 2nd, 3rd, and 6th months of follow-up (P < 0.001; <0.001; 0.003; <0.001, respectively). A total of 55 and 59 MAs were observed in the DME (mean = 99.40 ± 3.18 µm) and NDME (mean maximum diameter = 74.70 ± 2.86 µm) groups at baseline, respectively (significant between-group difference: P < 0.001). Blood flow signal was measurable for 46 (83.6%) and 34 (59.3%) eyes in the DME and NDME groups, respectively (significant between-group difference: P < 0.001). CONCLUSIONS: Compared to the NDME group, the DME group had larger MAs and a higher blood-flow signal ratio. Following anti-VEGF therapy, changes in the diameter of MAs were observed before changes in CMT thickness.
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Inibidores da Angiogênese , Retinopatia Diabética , Angiofluoresceinografia , Injeções Intravítreas , Edema Macular , Microaneurisma , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Humanos , Tomografia de Coerência Óptica/métodos , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Edema Macular/diagnóstico por imagem , Edema Macular/diagnóstico , Masculino , Microaneurisma/diagnóstico , Feminino , Pessoa de Meia-Idade , Inibidores da Angiogênese/uso terapêutico , Angiofluoresceinografia/métodos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Ranibizumab/uso terapêutico , Ranibizumab/administração & dosagem , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Fundo de Olho , SeguimentosRESUMO
BACKGROUND: In severe Proliferative Diabetic Retinopathy (PDR), fibrovascular membrane (FVM) causes macular tractional retinal detachment (MTRD) which threatens vision and eventually leads to blindness. Here we present a case of separation between the inner and outer retina in tractional retinoschisis, induced during intraoperative FVM delamination. CASE PRESENTATION: A 68-year-old woman presented with PDR in the right eye, characterized by a combined FVM and retinal detachment, for which a vitrectomy was performed. Multiple holes, large retinal detachment extending to all quadrants, and white-lined blood vessels with FVM were found during the procedure. When membrane delamination was performed, it strayed into the space between the inner and outer retinal layers without being noticed due to retinoschisis and multiple retinal holes. After removing the FVM and detaching the separated inner retina, fluid-gas and photocoagulation were performed. Retinal reattachment was successfully achieved after surgery, and the postoperative visual acuity was improved and maintained for 26 months postoperatively. CONCLUSIONS: When tractional retinoschisis due to FVM is combined with retinal holes in tractional retinal detachment (TRD), care must be taken to prevent delamination from straying into retinoschisis during separation.
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Retinopatia Diabética , Descolamento Retiniano , Retinosquise , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia , Humanos , Feminino , Idoso , Retinosquise/cirurgia , Retinosquise/etiologia , Retinosquise/diagnóstico , Retinopatia Diabética/cirurgia , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Vitrectomia/métodos , Acuidade Visual/fisiologia , Descolamento Retiniano/cirurgia , Descolamento Retiniano/etiologia , Descolamento Retiniano/diagnóstico , Perfurações Retinianas/cirurgia , Perfurações Retinianas/etiologia , Perfurações Retinianas/diagnóstico , Complicações IntraoperatóriasRESUMO
BACKGROUND: This research investigates the correlation between the severity of internal carotid artery (ICA) stenosis and retinal parameters in patients with proliferative diabetic retinopathy (PDR), aiming to uncover potential risk factors. METHODS: A retrospective analysis of 68 patients (136 eyes) diagnosed with bilateral PDR from January 1, 2017, to December 31, 2021, was conducted. Carotid artery stenosis (CAS) was assessed using neck computed tomography angiography (CTA) and carotid duplex ultrasound (CDUS), with stenosis classified into two groups: normal (group 1) and mild or above (group 2), based on the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Optical coherence tomography (OCT) and OCT angiography (OCTA) measured several retinal parameters, including sub foveal choroidal thickness (SFCT), retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, vessel density (VD), and foveal avascular zone (FAZ) area. Statistical analyses determined correlations between ICA degrees and retinal parameters. RESULTS: This study showed significant differences between groups in total VD, FAZ area, total RNFL thickness, and temporal RNFL thickness, indicating that patients with more severe ICA stenosis had noticeable retinal changes. Other parameters such as hyperlipidemia, total cholesterol levels, and intraocular pressure (IOP) also differed significantly, while no notable differences were observed in SFCT, central VD, average GCIPL, and superior, nasal, and inferior RNFL thickness. CONCLUSION: The study findings highlight retinal changes, such as an increased FAZ area, decreased total VD, and a total and thinner temporal RNFL, which suggest the need for carotid artery evaluation in patients. These findings have important clinical implications for the need for carotid work up in patients with PDR.
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Estenose das Carótidas , Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Constrição Patológica , Angiografia , Fatores de Risco , Vasos Retinianos , Angiofluoresceinografia/métodosRESUMO
PURPOSE: The objective was to predict proliferative diabetic retinopathy (PDR) in non-Hispanic Black (NHB) and Latino (LA) patients by applying machine learning algorithms to routinely collected blood and urine laboratory results. METHODS: Electronic medical records of 1124 type 2 diabetes patients treated at the Bronxcare Hospital eye clinic between January and December 2019 were analysed. Data collected included demographic information (ethnicity, age and sex), blood (fasting glucose, haemoglobin A1C [HbA1c] high-density lipoprotein [HDL], low-density lipoprotein [LDL], serum creatinine and estimated glomerular filtration rate [eGFR]) and urine (albumin-to-creatinine ratio [ACR]) test results and the outcome measure of retinopathy status. The efficacy of different machine learning models was assessed and compared. SHapley Additive exPlanations (SHAP) analysis was employed to evaluate the contribution of each feature to the model's predictions. RESULTS: The balanced random forest model surpassed other models in predicting PDR for both NHB and LA cohorts, achieving an AUC (area under the curve) of 83%. Regarding sex, the model exhibited remarkable performance for the female LA demographic, with an AUC of 87%. The SHAP analysis revealed that PDR-related factors influenced NHB and LA patients differently, with more pronounced disparity between sexes. Furthermore, the optimal cut-off values for these factors showed variations based on sex and ethnicity. CONCLUSIONS: This study demonstrates the potential of machine learning in identifying individuals at higher risk for PDR by leveraging routine blood and urine test results. It allows clinicians to prioritise at-risk individuals for timely evaluations. Furthermore, the findings emphasise the importance of accounting for both ethnicity and sex when analysing risk factors for PDR in type 2 diabetes individuals.
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Proliferative diabetic retinopathy (PDR), the most common type of diabetic retinopathy, is a main cause of visual and impairment blindness. Abnormal neovascularization, endothelial dysfunction, and vascular inflammation are important mechanisms for the development of PDR. Ets2 regulates angiogenesis-related genes and inflammation, however, the effect of Ets2 in PDR procession has not been clarified. Thus, this study is performed to investigate whether Ets2 exerts key functions in PDR. In this study, 10-week-old mice were used for establishing STZ-induced diabetic mice, and Ets2 expression was analyzed in retina tissues. Besides, newborn mice were applied to construct oxygen-induced retinopathy (OIR) models. The Ets2 expression, oxidative stress, and inflammation were detected in retina tissues. We found that Ets2 was highly expressed in retina tissues both in diabetic mice and OIR mice. Oxidative stress and inflammatory processes are two factors contributing to the pathogenesis of PDR. In retinal tissues of OIR mice, Ets2 knockdown inhibited expression of inflammatory mediators VEGFA, IL-6, and IL-8, and biomarkers of oxidative stress MCP-1, VCAM-1, and iNOS. ROS production was also inhibited by silencing Ets2. Ets2 deficiency inhibited endothelial cell proliferation in the retina. Furthermore, Ets2 knockdown contributed to suppressing the expression of angiogenesis-related genes VEGFA, JUNB, MMP-9, Tie2, Ang-2, and EphB4. Our study highlights that Ets2 accelerates PDR procession by promoting the proliferation of endothelial cells, oxidative stress, and inflammation, which provides a novel target against PDR.
RESUMO
Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes mellitus (DM). Anterior chamber (AC) flare and intraocular cytokines are potent biomarkers reflecting the intraocular immune status in PDR. This study aimed to elucidate the complex interrelationship between AC flare and intraocular cytokines in PDR eyes. A retrospective observational study was conducted on 19 PDR eyes of 19 patients with type 2 DM, and on 19 eyes of 19 patients with idiopathic macular hole or epiretinal membrane as controls. AC flare was measured before pars plana vitrectomy (PPV). Aqueous humor (AH) and vitreous fluid (VF) samples were collected at the time of PPV, and the quantities of 27 cytokines in both intraocular fluids were analyzed. In the PDR and control groups, Spearman's rank correlation analysis revealed a positive correlation between AC flare and IL-8 level in both AH and VF. Additionally, IL-8 levels in AH correlated positively with IL-8 levels in VF. In the PDR group, receiver operating characteristic curve analysis identified IL-8 level in AH as a significant predictor for both diabetic macular edema (DME) and vitreous hemorrhage (VH) complications. The cut-off values of IL-8 were established at ≥26.6 pg/mL for DME and ≥7.96 pg/mL for VH. Given the positive correlation between AC flare and AH IL-8 level, the present findings suggest that AC flare value may potentially be a non-invasive biomarker for predicting DME.
Assuntos
Câmara Anterior , Humor Aquoso , Retinopatia Diabética , Corpo Vítreo , Humanos , Retinopatia Diabética/imunologia , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Retinopatia Diabética/etiologia , Masculino , Feminino , Câmara Anterior/patologia , Câmara Anterior/metabolismo , Câmara Anterior/imunologia , Pessoa de Meia-Idade , Idoso , Humor Aquoso/metabolismo , Humor Aquoso/imunologia , Estudos Retrospectivos , Corpo Vítreo/metabolismo , Corpo Vítreo/patologia , Edema Macular/etiologia , Edema Macular/metabolismo , Edema Macular/imunologia , Edema Macular/patologia , Vitrectomia , Biomarcadores , Citocinas/metabolismo , Interleucina-8/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/imunologia , Curva ROCRESUMO
Fatty acid-binding proteins (FABPs), a family of lipid chaperone molecules that are involved in intracellular lipid transportation to specific cellular compartments, stimulate lipid-associated responses such as biological signaling, membrane synthesis, transcriptional regulation, and lipid synthesis. Previous studies have shown that FABP4, a member of this family of proteins that are expressed in adipocytes and macrophages, plays pivotal roles in the pathogenesis of various cardiovascular and metabolic diseases, including diabetes mellitus (DM) and hypertension (HT). Since significant increases in the serum levels of FABP4 were detected in those patients, FABP4 has been identified as a crucial biomarker for these systemic diseases. In addition, in the field of ophthalmology, our group found that intraocular levels of FABP4 (ioFABP4) and free fatty acids (ioFFA) were substantially elevated in patients with retinal vascular diseases (RVDs) including proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO), for which DM and HT are also recognized as significant risk factors. Recent studies have also revealed that ioFABP4 plays important roles in both retinal physiology and pathogenesis, and the results of these studies have suggested potential molecular targets for retinal diseases that might lead to future new therapeutic strategies.
Assuntos
Proteínas de Ligação a Ácido Graxo , Humanos , Proteínas de Ligação a Ácido Graxo/metabolismo , Proteínas de Ligação a Ácido Graxo/genética , Animais , Doenças Retinianas/metabolismo , Retina/metabolismo , Retinopatia Diabética/metabolismoRESUMO
PURPOSE: To evaluate the effect of adjuvant Mitomycin C (MMC) use on the anatomical and functional success of vitreoretinal surgery (VRS) in severe diabetic tractional retinal detachment (dTRD) patients. METHODS: A retrospective analysis of consecutive patients undergoing VRS due to severe dTRD was conducted. Patients were categorized into those who received 20 µg/0.1 mL MMC via MMC sandwich method (Group 1) and those who did not (Group 2). Demographics, surgical characteristics, visual outcomes, and complications that may related to MMC were analyzed. RESULTS: A total of 25 eyes were included, 13 in Group 1 and 12 in Group 2. No statistical difference was observed in baseline characteristics between the groups. The mean best-corrected visual acuity was 1.90 ± 0.43 logMAR and 1.93 ± 0.41 logMAR preoperatively and 1.60 ± 0.78 logMAR and 1.56 ± 0.78 logMAR postoperatively in Groups 1 and 2, respectively (p = 0.154). The postoperative mean intraocular pressure was 16.23 ± 2.55 mmHg and 13.08 ± 4.94 mmHg in Groups 1 and 2, respectively (p = 0.225). The rate of re-surgery was significantly lower in Group 1 (0% vs. 41.7% in Group 2, p = 0.015). Retina was attached in all patients at the last visit. No MMC-related complication was recorded. CONCLUSION: Intraoperative adjuvant MMC application for severe dTRD significantly reduces re-surgery rates with good anatomical and functional outcomes safely.