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PURPOSE: To test the hypothesis that optical coherence tomography (OCT) choroidal hypertransmission width (CHW) is a prognostic biomarker in idiopathic macular hole (MH) surgery METHODS: Retrospective cohort study of consecutive patients undergoing successful pars plana vitrectomy for idiopathic MH. We collected demographic, clinical, and OCT variables at the preoperative and last available visits. Two investigators assessed the following OCT parameters: MH minimum diameter, base diameter, CHW, ellipsoid zone, and external limiting membrane status (absent vs. present). Delta CHW was calculated as the difference between CHW and MH minimum diameter. Linear models were used to investigate factors associated with postoperative best-corrected visual acuity (BCVA) and BCVA change. RESULTS: Thirty-six eyes (36 patients) with a median (interquartile range (IQR)) follow-up of 9 (8-11) months were included. The median BCVA (IQR) improved from 0.75 (1-0.6) logMAR preoperatively to 0.2 (0.6-0.1) logMAR at the last visit (p < 0.001). Preoperative MH minimum diameter (for a 10-µm increase, estimate (standard error (SE)): 0.009 (0.003) logMAR, p = 0.003), base diameter (for a 10-µm increase, 0.003 (0.001) logMAR, p = 0.032), CHW (for a 10-µm increase, 0.008 (0.002) logMAR, p < 0.001), and delta CHW (for a 10-µm increase, 0.013 (0.005) logMAR, p = 0.009) were significantly associated with postoperative BCVA. The proportion of variance explained was the highest for MH CHW (R2 0.35), followed by minimum MH diameter (R2 0.24), delta CHW (R2 0.19), and MH base diameter (R2 0.14). None of the study variables was associated with delta BCVA. CONCLUSION: Preoperative CHW is associated with postoperative visual acuity in patients undergoing successful idiopathic MH surgery and may be a useful OCT prognostic biomarker.
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Coroides , Perforaciones de la Retina , Tomografía de Coherencia Óptica , Agudeza Visual , Vitrectomía , Humanos , Tomografía de Coherencia Óptica/métodos , Perforaciones de la Retina/cirugía , Perforaciones de la Retina/diagnóstico , Perforaciones de la Retina/fisiopatología , Estudios Retrospectivos , Masculino , Femenino , Vitrectomía/métodos , Agudeza Visual/fisiología , Coroides/diagnóstico por imagen , Pronóstico , Anciano , Estudios de Seguimiento , Persona de Mediana Edad , Periodo Posoperatorio , BiomarcadoresRESUMEN
INTRODUCTION: Intravitreal dexamethasone (DEX) implant is indicated for the treatment of macular oedema due to diabetic retinopathy, retinal vein occlusion and uveitis. The most common complications are cataract and elevated intraocular pressure (IOP). Accidental injection of DEX implant into the lens is a rare complication and only few papers presented it. CASE PRESENTATION: A 40-year-old man was treated with DEX implant for diabetic macular oedema in both eyes. At 1 week follow-up visit, slit lamp examination showed the DEX implant was located in the crystalline lens of the right eye (RE) without any sign of inflammation, cataract or elevated IOP, so we decided to plan a normal follow-up schedule. Macular oedema relapsed 5 months after the injection in the left eye (LE), whereas the RE did not show any sing of intraretinal or subretinal fluid. Six months after DEX implantation an uneventful phacoemulsification and intraocular lens placement were performed in the RE because of IOP elevation. CONCLUSIONS: The therapeutic effect of DEX implant can be maintained for a longer period of time than intravitreal implant, determining complete reabsorption of macular oedema. Intralenticular implant can be maintained inside the lens until either IOP increases, cataract progresses, or other complications occur.
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Catarata , Retinopatía Diabética , Edema Macular , Masculino , Humanos , Adulto , Dexametasona , Glucocorticoides , Edema Macular/diagnóstico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Estudios de Seguimiento , Inyecciones Intravítreas , Catarata/inducido químicamente , Catarata/complicaciones , Retinopatía Diabética/complicaciones , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/tratamiento farmacológico , Implantes de Medicamentos/efectos adversos , Resultado del TratamientoRESUMEN
Optical coherence tomography angiography (OCTA) is an innovative and reliable technique detecting the early preclinical retinal vascular change in patients with diabetes. We have designed our study to evaluate whether an independent relationship exists between continuous glucose monitoring (CGM)-derived glucose metrics and OCTA parameters in young adult patients with type 1 diabetes without diabetic retinopathy (DR). Inclusion criteria were age ≥ 18 years, diagnosis of type 1 diabetes from ≥ 1 year, stable insulin treatment in the last three months, use of real-time CGM, and CGM wear time ≥ 70%. Each patient underwent dilated slit lamp fundus biomicroscopy to exclude the presence of DR. A skilled operator performed OCTA scans in the morning to avoid possible diurnal variation. CGM-derived glucose metrics from the last 2 weeks were collected through the dedicated software during OCTA. Forty-nine patients with type 1 diabetes (age 29 [18; 39] years, HbA1c 7.7 ± 1.0%) and 34 control subjects participated in the study. Vessel density (VD) of the whole image and parafoveal retina in the superficial (SCP) and deep capillary plexus (DCP) was significantly lower in patients with type 1 diabetes compared to controls. The coefficient of variation of average daily glucose, evaluated by CGM, significantly correlated with foveal and parafoveal VD in SCP and with foveal VD in DCP. High glucose variability might be responsible for the early increase of VD in these areas. Prospective studies may help understand if this pattern precedes DR. The difference we detected between patients with and without diabetes confirms that OCTA is a reliable tool for detecting early retinal abnormalities.
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Diabetes Mellitus Tipo 1 , Retinopatía Diabética , Adulto Joven , Humanos , Adolescente , Adulto , Diabetes Mellitus Tipo 1/diagnóstico , Retinopatía Diabética/diagnóstico , Angiografía con Fluoresceína/métodos , Vasos Retinianos , Estudios Prospectivos , Benchmarking , Automonitorización de la Glucosa Sanguínea , Glucemia , Tomografía de Coherencia Óptica/métodosRESUMEN
Introduction: Respiratory insufficiency is one of the main causes of death in myotonic dystrophy type 1 (DM1). Although there is general consensus that these patients have a restrictive ventilatory pattern, hypoventilation, chronic hypercapnia, and sleep disturbances, the prevalence of respiratory disease and indication for the effects of noninvasive ventilation (NIV) need to be further explored. Objectives: To describe respiratory function and need for NIV at baseline and over time in a cohort of adult patients with DM1. Methods: A total of 151 adult patients with DM1 were subjected to arterial blood gas analysis, sitting and supine forced vital capacity (FVC), peak cough expiratory flow (PCEF), nocturnal oximetry, and maximal inspiratory pressure and expiratory pressure (MIP/PEP). Results: On first assessment, 84 of 151 had normal respiratory function (median age: 38 years, median BMI: 23.9, and median disease duration: 11 years); 67 received an indication to use NIV (median age: 49 years, median BMI: 25,8, and median disease duration: 14 years). After a median time of 3.85 years, 43 patients were lost to follow-up; 9 of 84 required NIV; only 17 of 67 with the new NIV prescription were adherent. Conclusions: We provide additional data on the natural history of respiratory function decline and treatment adherence in a relatively large cohort of well-characterized patients with DM1. A high proportion (28%) was lost to follow-up. A minority (11%) required NIV, and only 25% were treatment adherent, irrespective of specific demographics and respiratory features. Our results also confirm previous findings, showing that age, disease duration, and higher BMIs are predisposing factors for respiratory impairment.
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Distrofia Miotónica , Ventilación no Invasiva , Insuficiencia Respiratoria , Adulto , Humanos , Hipercapnia/etiología , Hipercapnia/terapia , Persona de Mediana Edad , Distrofia Miotónica/complicaciones , Distrofia Miotónica/terapia , Respiración , Insuficiencia Respiratoria/terapiaRESUMEN
INTRODUCTION: To compare the functional and anatomic outcomes between eyes in patients with diabetic macular edema (DME) who underwent a complete anti-vascular endothelial growth factor (VEGF) loading dose with aflibercept and those who were switched to dexamethasone intravitreal (DEX) implant after an incomplete anti-VEGF treatment regimen during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This was a retrospective and comparative study conducted on patients with DME. Main outcome measures were mean change in best corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 4. RESULTS: Forty-three eyes (23 eyes in the anti-VEGF group and 20 eyes in the DEX group) were included. Mean BCVA significantly improved from 37.7 ± 25.3 and 35.7 ± 22.0 letters at baseline to 45.4 (23.9) (mean adjusted BCVA improvement 7.6 ± 20.8 letters, p = 0.033) and 46.1 ± 26.0 (mean adjusted BCVA improvement 10.6 ± 15.9 letters, p = 0.049) at month 4 in the anti-VEGF and DEX groups, respectively, with no significant differences between study groups (mean adjusted BCVA difference 2.8 letters, 95% CI - 9.4 to 14.9 letters, p = 0.648). There were no statistically significant differences in the proportion of eyes that achieved a BCVA improvement of ≥ 5, ≥ 10, and ≥ 15 letters between groups. CRT was significantly reduced from baseline to month 4 in both DEX (mean adjusted CRT reduction 167.3 ± 148.2 µm, p = 0.012) and anti-VEGF groups (mean adjusted CRT reduction 109.9 ± 181.9 µm, p < 0.001), with no differences between them (mean adjusted CRT difference 56.1 µm, 95% CI - 46.0 to 158.2 µm, p = 0.273). Of 20 eyes in the DEX group, 16 (80.0%) and 9 (45.0%) eyes achieved a CRT reduction of ≥ 20% from baseline at 2 months and at 4 months, respectively. CONCLUSIONS: Our results seem to suggest that DEX implant can significantly improve both functional and anatomic clinical outcomes in patients who were unable to complete anti-VEGF loading dose during the COVID-19 pandemic.
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BACKGROUND: To report the first Italian case of hypotrichosis with juvenile macular dystrophy complicated by macular neovascularization diagnosed through multimodal imaging. CASE PRESENTATION: An 11-year-old boy was referred to our Institution for bilateral maculopathy of unknown origin. Multimodal imaging helps the diagnosis of Juvenile Macular Dystrophy with Hypotrichosis (HJMD). Fundus examination showed several alterations of the retinal pigment epithelium and circular pigmented area of chorioretinal atrophy. Structural spectral domain optical coherence tomography (OCT) showed some backscattering phenomenon with several alterations of retinal pigment epithelium and photoreceptor layer in both eyes. Moreover, OCT showed hyperreflective lesion beneath the neuroepithelium in left eye. OCT angiography (OCT-A) revealed a pathologic neovascular network in choriocapillaris plexus, probably the result of a fibrovascular membrane. Multifocal electroretinograms (MfERGs) showed functional alterations in 12.22° of the central retina. In order to confirm the suspicion of HJMD, the child and both parents underwent genetic testing. Both parents resulted to be heterozygous healthy carriers of a single variation. CONCLUSION: Multimodal imaging, in particular OCT-A, is a useful aid, along to clinical findings and genetics, for the diagnosis of inherited retinal dystrophies.
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Hipotricosis , Degeneración Macular , Distrofias Retinianas , Niño , Angiografía con Fluoresceína , Humanos , Masculino , Imagen Multimodal , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/genética , Epitelio Pigmentado de la Retina , Tomografía de Coherencia ÓpticaRESUMEN
OBJECTIVES: To investigate subclinical and clinical abnormalities in retinal and choroidal vascular plexuses in patients with SSc by means of optical coherence tomography angiography (OCT-A). METHODS: A total of 20 consecutive SSc patients were recruited and compared with 20 healthy subjects. Quantitative analysis of vessel density (VD), choriocapillaris plexus flow index (CCP-FI) and choroidal vascularity index were performed on OCT-A images in the superficial capillary plexus (SCP), deep capillary plexus (DCP) and CCP for all patients. Images were further reviewed by two independent readers for the assessment of qualitative abnormalities, including tortuosity, rarefaction areas, megacapillaries and macular-foveal capillaries. RESULTS: The DCP-VD in the whole scan and in the perifoveal, superior, inferior, nasal and temporal regions was significantly lower in the SSc group. The CCP-FI was significantly higher in SSc patients. When comparing SSc patients with and without digital ulcers, significantly decreased SCP-VD was demonstrated in the whole, perifoveal, superior, inferior, temporal and nasal regions. No difference in any of the OCT-A parameters was observed when comparing patients with and without interstitial lung disease. Qualitative analysis of OCT-A revealed at least one abnormality in 95% of patients. CONCLUSION: We showed the ability of OCT-A to disclose early ocular vascular abnormalities in patients with SSc. Our results may represent a hypothesis-generating basis for exploring the potential role of OCT-A in diagnosis, monitoring and prognosis stratification in SSc.
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Angiografía con Fluoresceína/métodos , Microcirculación/fisiología , Retina/diagnóstico por imagen , Enfermedades de la Retina/diagnóstico , Vasos Retinianos/fisiopatología , Esclerodermia Sistémica/complicaciones , Capilares/diagnóstico por imagen , Capilares/fisiopatología , Fondo de Ojo , Humanos , Pronóstico , Retina/fisiopatología , Enfermedades de la Retina/etiología , Enfermedades de la Retina/fisiopatología , Vasos Retinianos/diagnóstico por imagen , Esclerodermia Sistémica/diagnóstico , Tomografía de Coherencia Óptica/métodosRESUMEN
In chronic hemodialysis (HD) patients, intradialytic hypotension (IDH) is a complication that increases mortality risk. We run a pilot study to analyzing possible relationships between optical coherence tomography angiography (OCT-A) metrics and IDH with the aim of evaluating if OCT-A could represent a useful tool to stratify the hypotensive risk in dialysis patients. A total of 35 eyes (35 patients) were analyzed. OCT-A was performed before and after a single dialysis session. We performed OCT-A 3 × 3 mm and 6 × 6 mm scanning area focused on the fovea centralis. Patients were then followed up to 30 days (10 HD sessions) and a total of 73 IDHs were recorded, with 12 patients (60%) experiencing at least one IDH. Different OCT-A parameters were reduced after dialysis: central choroid thickness (CCT), 6 × 6 mm foveal whole vessel density (VD) of superficial capillary plexus (SPC) and 6 × 6 mm foveal VD of deep capillary plexus (DCP). At logistic regression analysis, IDH was positively associated with baseline foveal VD of SCP and DCP, while an inverse association was found with the choroid. In Kaplan-Meier analyses of patients categorized according to the ROC-derived optimal thresholds, CCT, the 3 × 3 foveal VD of SCP, the 3 × 3 mm and 6 × 6 mm foveal VD of DCP and the 6 × 6 mm foveal VD of SCP were strongly associated with a higher risk of IDH over the 30-days follow-up. In HD patients, a single OCT-A measurement may represent a non-invasive, rapid tool to evaluate the compliance of vascular bed to HD stress and to stratify the risk of IDH in the short term.
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Hipotensión/diagnóstico por imagen , Diálisis Renal , Tomografía de Coherencia Óptica , Anciano , Femenino , Fóvea Central/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Diálisis Renal/efectos adversos , Tomografía de Coherencia Óptica/métodosRESUMEN
We report our experience during COVID-19 outbreak for intravitreal injections in patients with maculopathy. We proposed a treatment priority levels and timings; the "High" priority level includes all monocular patients; the "Moderate" is assigned to all patients with an active macular neovascularization; the patients affected by diabetic macular edema or retinal vein occlusion belong to the "Low" class. This organization allowed us to treat the most urgent patients although the injections performed had a 91.7% drop compared to the same period of 2019.
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COVID-19/epidemiología , Brotes de Enfermedades , Prioridades en Salud/organización & administración , Preparaciones Farmacéuticas/administración & dosificación , Enfermedades de la Retina/clasificación , SARS-CoV-2 , Centros de Atención Terciaria/organización & administración , Coriorretinopatía Serosa Central/clasificación , Coriorretinopatía Serosa Central/tratamiento farmacológico , Retinopatía Diabética/clasificación , Retinopatía Diabética/tratamiento farmacológico , Humanos , Inyecciones Intravítreas , Italia/epidemiología , Degeneración Macular/clasificación , Degeneración Macular/tratamiento farmacológico , Edema Macular/clasificación , Edema Macular/tratamiento farmacológico , Cuarentena , Enfermedades de la Retina/tratamiento farmacológico , Oclusión de la Vena Retiniana/clasificación , Oclusión de la Vena Retiniana/tratamiento farmacológicoRESUMEN
PURPOSE: To assess changes on optical coherence tomography (OCT) angiography in diabetic macular edema (DME) treated with subthreshold micropulse yellow laser (SMPL) over a period of 6 months. METHODS: Thirty-five eyes (35 consecutive patients) with treatment-naive DME prospectively underwent (at baseline, 3 and 6 months) best-corrected visual acuity, swept-source OCT angiography/OCT, and fundus autofluorescence. Following parameters were evaluated on OCT angiography in the superficial capillary plexus (SCP) and deep capillary plexus (DCP): the area of foveal avascular zone, number of microaneurysms (MA), area of cysts, and presence of capillary network alterations. Microaneurysm change was also evaluated in 15 fellow eyes, not needing treatment over 6 months. Vessel and perfusion densities were evaluated in the SCP, DCP, and choriocapillaris, with image J. Retina thickness, number of hyperreflective retinal spots, and external limiting membrane integrity were evaluated on OCT. All measurements were performed by two masked graders, independently. RESULTS: All patients had diabetes mellitus Type 2 (mean age, 69.4 ± 10.9 years; duration of diabetes mellitus, 15.7 ± 8.7 years; and HbA1c 7.7 ± 1.2%). Mean best-corrected visual acuity at baseline was 69.7 ± 12.0 letters ETDRS, 72.7 ± 10.7 at 3 months (gain 3.1 ± 4.3, P = 0.0049) and 74.3 ± 9.5 at 6 months (gain 4.6 ± 7.2, P < 0.0001). Foveal avascular zone area decreased in the DCP at 6 months (P = 0.01). Area of cysts decreased in the SCP at 3 months and 6 months (P = 0.038; P = 0.049), and in the DCP at 6 months (P = 0.0071). Number of MA decreased at 6 months in the SCP (P = 0.0007) and at 3 months and 6 months in the DCP (P = 0.048; P < 0.0001) in treated eyes. No significant change in number of MA was found in nontreated eyes. There was no statistically significant change in any other OCT angiography/OCT parameter. CONCLUSION: Subthreshold micropulse yellow laser induces more pronounced changes in the DCP than in the SCP in DME. These changes occurred as early as 3 months after treatment. The evaluation of specific parameters in the DCP may help in determining treatment response.
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Retinopatía Diabética/diagnóstico , Angiografía con Fluoresceína/métodos , Terapia por Láser/métodos , Mácula Lútea/patología , Edema Macular/diagnóstico , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Anciano , Retinopatía Diabética/complicaciones , Retinopatía Diabética/cirugía , Femenino , Estudios de Seguimiento , Fondo de Ojo , Humanos , Edema Macular/etiología , Edema Macular/cirugía , Masculino , Estudios ProspectivosRESUMEN
Optical coherence tomography angiography (OCT-A) has recently improved the ability to detect subclinical and early clinically visible microvascular changes occurring in patients with diabetes mellitus (DM). The aim of the present study is to evaluate and compare early quantitative changes of macular perfusion parameters in patients with DM without DR and with mild nonproliferative DR (NPDR) evaluated by two different swept-source (SS) OCT-A instruments using two scan protocols (3 × 3 mm and 6 × 6 mm). One hundred eleven subjects/eyes were prospectively evaluated: 18 healthy controls (control group), 73 eyes with DM but no DR (no-DR group), and 20 eyes with mild NPDR (DR group). All quantitative analyses were performed using ImageJ and included vessel and perfusion density, area and circularity index of the FAZ, and vascular complexity parameters. The agreement between methods was assessed according to the method of Bland-Altman. A significant decrease in the majority of the considered parameters was found in the DR group versus the controls with both instruments. The results of Bland-Altman analysis showed the presence of a systemic bias between the two instruments with PLEX Elite providing higher values for the majority of the tested parameters when considering 6 × 6 mm angiocubes and a less definite difference in 3 × 3 mm angiocubes. In conclusion, this study documents early microvascular changes occurring in the macular region of patients at initial stages of DR, confirmed with both SS OCT-A instruments. The fact that early microvascular alterations could not be detected with one instrument does not necessarily mean that these alterations are not actually present, but this could be an intrinsic limitation of the device itself. Further, larger longitudinal studies are needed to better understand microvascular damage at very early stages of diabetic retinal disease and to define the strengths and weaknesses of different OCT-A devices.
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Diabetes Mellitus/fisiopatología , Retinopatía Diabética/diagnóstico por imagen , Microcirculación , Tomografía de Coherencia Óptica/instrumentación , Tomografía de Coherencia Óptica/métodos , Adulto , Anciano , Estudios de Casos y Controles , Proliferación Celular , Humanos , Mácula Lútea/diagnóstico por imagen , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Purpose: To evaluate peripapillary vessel density and morphology in patients with diabetes mellitus (DM) without clinical signs of diabetic retinopathy (DR) and with mild, nonproliferative DR and to correlate with peripapillary nerve fiber layer (NFL) thickness. Methods: One hundred seventeen eyes (34 healthy controls, 54 patients with DM without DR [noDR group] and 24 patients with mild DR [DR group]) were prospectively evaluated. All subjects underwent peripapillary and macular optical coherence tomography angiography (OCT-A). Peripapillary NFL thickness was also recorded. OCT-A slab of radial peripapillary plexus (RPC) and macular superficial capillary plexus (SCP) were analysed in order to calculate perfusion density (PD) and vessel density (VD). Further an image analysis of RPC slab was performed to identify number of branches (NoB) and total branches length (tBL). Results: In peripapillary area there was a significant decrease in VD (P = 0.003), NoB (P < 0.001), and tBL (P < 0.001) in noDR group versus controls; PD values were not different among groups (P = 0.126); there was a significant decrease in average NFL thickness in DR versus controls (P = 0.008) and in the inferior quadrant in noDR group versus controls (P = 0.03); there was a significant correlation between OCT-A and NFL thickness values (ρ ranging from 0.19-0.57). In macular region PD and VD were decreased only in DR group (P < 0.05). Conclusions: There are early changes in the peripapillary vessel morphology and VD of the RPC in patients with DM without DR that correlate to NFL thinning. Earlier changes in superficial vessel density are documented in the peripapillary than in the macular region. These data may confirm a coexistence of an early neuronal and microvascular damage in patients with DM without clinical signs of DR.
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Diabetes Mellitus/patología , Retinopatía Diabética/patología , Fibras Nerviosas/patología , Disco Óptico/irrigación sanguínea , Células Ganglionares de la Retina/patología , Vasos Retinianos/patología , Adulto , Anciano , Presión Sanguínea/fisiología , Estudios de Casos y Controles , Estudios Transversales , Diabetes Mellitus/diagnóstico por imagen , Retinopatía Diabética/diagnóstico por imagen , Femenino , Angiografía con Fluoresceína , Hemoglobina Glucada/metabolismo , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía de Coherencia Óptica , Campos VisualesRESUMEN
BACKGROUND/AIMS: the anti-vascular endothelial growth factors (VEGF), Aflibercept and Ranibizumab, are used for the treatment of macular degeneration. Here we examined the involvement of nitric oxide (NO), mitochondria function and of apoptosis/autophagy in their antioxidant effects in human retinal pigment epithelium cells (RPE). METHODS: RPE were exposed to Ranibizumab/Aflibercept in the absence or presence of NO synthase (NOS) inhibitor and of autophagy activator/blocker, rapamicyn/3-methyladenine. Specific kits were used for cell viability, NO and reactive oxygen species detection and mitochondrial membrane potential measurement, whereas Western Blot was performed for apoptosis/ autophagy markers and other kinases detection. RESULTS: In RPE cultured in physiological conditions, Aflibercept/Ranibizumab increased NO release in a dose and time-dependent way. Opposite results were obtained in RPE pretreated with hydrogen peroxide. Moreover, both the anti-VEGF agents were able to prevent the fall of cell viability and of mitochondrial membrane potential. Those effects were reduced by the NOS inhibitor and 3-methyladenine and were potentiated by rapamycin. Finally, Aflibercept and Ranibizumab counteracted the changes of apoptosis/autophagy markers, NOS, Phosphatidylinositol-3-Kinase/Protein Kinase B and Extracellular signal-regulated kinases 1/2 caused by peroxidation. CONCLUSION: Aflibercept and Ranibizumab protect RPE against peroxidation through the modulation of NO release, apoptosis and autophagy.
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Inhibidores de la Angiogénesis/farmacología , Autofagia/efectos de los fármacos , Óxido Nítrico/metabolismo , Ranibizumab/farmacología , Proteínas Recombinantes de Fusión/farmacología , Adenina/análogos & derivados , Adenina/toxicidad , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Peróxido de Hidrógeno/toxicidad , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular , Epitelio Pigmentado de la Retina/citología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/metabolismo , Sirolimus/toxicidad , PorcinosRESUMEN
The objective of our study was to perform a randomized controlled trial (RCT) aimed to evaluate the effects of three strictly monitored exercise programs(SMEP) compared to "usual care" (UCP) in a cohort of ALS patients. We included patients with definite and probable ALS and disease duration ≤24 months. Patients were randomized to receive a SMEPs or a UCP. SMEPs included three subgroups of treatment: active exercises associated with cycloergometer activity (1A), only active (1B) and passive (1C) exercises, respectively. Moreover, SMEP patients and their caregivers were trained to a daily home-based passive exercise program. The UCP group was treated with passive and stretching exercises twice weekly. The treatment period for both groups was 6 months (T180), and patients were assessed by revised ALS Functional Rating Scale (ALSFRS-R), % Forced Vital Capacity (FVC %), and McGill Quality of Life (MGQoL) questionnaire. ALSFRS-R score was also evaluated at 6 months after the treatment period (T360). Sixty ALS patients were randomly assigned to one of two arms: SMEP Group included 30 patients, ten subjects for each subgroup (1A, 1B, and 1C); 30 patients were included in the UCP Group.At T180 and T360, SMEPs group had significantly higher ALSFRS-R score compared to the UCP group (32.8 ± 6.5 vs 28.7 ± 7.5, p = 0.0298; 27.5 ± 7.6 vs 23.3 ± 7.6, p = 0.0338, respectively). No effects of SMEPs on survival, respiratory decline and MGQol were found. In conclusion, although no effect on survival was demonstrated,our data suggest that a strictly monitored exercise program may significantly reduce motor deterioration in ALS patients.
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Esclerosis Amiotrófica Lateral/rehabilitación , Progresión de la Enfermedad , Terapia por Ejercicio/métodos , Evaluación de Resultado en la Atención de Salud , Índice de Severidad de la Enfermedad , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Método Simple CiegoRESUMEN
BACKGROUND: Nephrotic syndrome is a condition that is clinically associated with poor outcome. In this study, we compared different techniques of urine sample preparation in order to develop a robust analytical protocol to define the differential urinary proteome of urinary abnormalities compared to nephrotic proteinuria. METHODS: We recruited 5 normal control subjects, 16 patients with urinary abnormalities and 16 patients with nephrotic syndrome. Proteins from normal urine were processed using three different protocols [acetone, ultrafiltration and trichloroacetic acid (TCA) precipitation], depletion of albumin and IgGs and then analysed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) gels and mass spectrometry. RESULTS: Comparing the three extraction methods by visual inspection of gels after 2D gel electrophoresis, the acetone precipitation and TCA methods yielded the best quality of protein extraction, while the acetone precipitation method was the most efficient. Furthermore, we tested three commercial kits for albumin and IgG depletion. We applied the optimized acetone extraction protocol to compare urinary samples from nephrotic patients (NP) to urinary samples obtained from patients presenting with urinary abnormalities (UAP). We observed a proteolytic activity directed against albumin. This observation was more prevalent in urinary samples from NP than from UAP. Within both groups, there was some inter-individual variability in the observed proteolytic activity. An increased concentration of alpha1 antitrypsin was also observed in urine of NP. We analysed albumin fragmentation by 1D and 2D western blots in the same samples skipping the albumin and IgG depletion steps to avoid the possible confound of albumin fragment removal. The analysis confirmed a stronger proteolytic activity in the nephrotic group. CONCLUSIONS: The proteolytic activity against albumin and the anti-proteolytic activity of alpha1 antitrypsin are likely linked and could play an important role in the nephrotic process. If replicated in larger samples, this methodology may lead to a better understanding of the underlying pathophysiological process of nephrotic syndrome.
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Albúminas/metabolismo , Síndrome Nefrótico/orina , Péptido Hidrolasas/orina , Proteinuria/orina , Proteómica , Adulto , Anciano , Estudios de Casos y Controles , Electroforesis en Gel Bidimensional , Femenino , Humanos , Inmunoglobulina G/orina , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Síndrome Nefrótico/fisiopatología , Variaciones Dependientes del Observador , Proteinuria/fisiopatología , alfa 1-Antitripsina/orinaRESUMEN
An increased free-radical production has been documented during hemodialysis (HD) particularly when bio-incompatible membranes are utilized. These highly reactive free radicals can cause damage through several pathways, one of the best known being lipid peroxidation. Malondialdehyde (MDA) is a product of lipid peroxidation, which can partly be removed by HD due to its low molecular weight and water solubility. Hydroperoxides are predominantly found in lipid substances, and therefore their removal by HD could be difficult. We evaluated the behavior of these two by-products of lipid peroxidation during HD, comparing their behavior in three different membranes, in order to study their reliability as markers of acute oxidative injury. Fifteen stable HD patients were dialyzed with each of the following membranes: cuprophan, polyamide, and polysulfone, three sessions for every membrane. MDA and hydroperoxides were measured pre-HD and then both from the arterial and venous line at 8, 15, 30, and 240 min. During HD with cuprophan membrane MDA decreased significantly in the venous line compared with the arterial line at 8, 15, and 30 min (P < 0.05). At the end of HD, MDA was significantly reduced compared with MDA pre-HD (P < 0.05). Plasma hydroperoxides increased significantly in the venous line compared with the arterial line at 8, 15, 30, and 240 min (P < 0.05). At the end of HD, hydroperoxides had increased significantly as compared with pre-HD (P < 0.05). When the polyamide and polysulfone membranes were used, the behavior of MDA was similar to that found with cuprophan. Hydroperoxides were unchanged during HD using both membranes. MDA is not a reliable marker of acute oxidative injury during HD as it is removed during HD. Hydroperoxide measurement is a better marker of acute oxidative injury during HD.
Asunto(s)
Peróxidos Lipídicos/sangre , Malondialdehído/sangre , Estrés Oxidativo , Diálisis Renal/efectos adversos , Anciano , Materiales Biocompatibles , Biomarcadores/sangre , Celulosa/análogos & derivados , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Masculino , Membranas Artificiales , Nylons , Polímeros , SulfonasRESUMEN
An increase in conjugated linoleic acid (CLA), a natural fatty acid present in our diet, which possesses anticarcinogenic and antiatherogenic activities in experimental models, has been found in both the plasma and adipose tissue of end-stage chronic renal failure (ESCRF) patients. Increased levels of retinol have also been found in those patients, due to a reduced excretion of the retinol-binding protein. Since retinol is known to influence lipid metabolism, we evaluated whether changes in retinol, CLA, and other fatty acids are correlated in the plasma of CRF patients. We measured CLA, retinol, and unsaturated fatty acids in the plasma of the following groups: (A) 35 ESCRF patients; (B) 20 hemodialysis (HD) patients; (C) 20 healthy controls. Subjects with total cholesterol and/or triglycerides higher than 250 mg/dL were excluded. We found a significant increase in CLA, retinol, palmitoleic (16:1), and oleic (18:1) acids in ESCRF patients. In HD patients we found a similar pattern, however, CLA increase was not significant. No changes were observed in the other fatty acids measured. In the groups of ESCRF and HD patients, a positive correlation between the levels of plasma retinol and CLA, and between retinol and 16:1 was found. These correlations were not detected in controls. The abnormal levels of plasma retinol in CRF patients might partly explain the changes in CLA and 16:1. The influence of retinol levels on these fatty acids might be due to an induction of delta 9 desaturase. In fact, 16:1 is known to be produced, partly, by delta 9 desaturation of palmitic acid. Moreover, the formation of CLA from delta 9 desaturation of vaccenic acid-a trans-monounsaturated fatty acid present in our diet-has recently been demonstrated in humans. Nevertheless, our data do not represent direct evidence supporting an increased delta 9 desaturase activity in CRF patients. Another possible explanation might be a variation in the exogenous intake.