Search

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.

Abstract 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.

Abstract 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.

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.

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.

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.

Optical coherence tomography angiography (OCTA) is a non-invasive diagnostic instrument that has become indispensable for the management of age-related macular degeneration (AMD). OCTA allows quickly visualizing retinal and choroidal microvasculature, and in the last years, its use has increased in clinical practice as well as for research into the pathophysiology of AMD. This review provides a discussion of new technology and application of OCTA in intermediate and late AMD.

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. [ABSTRACT FROM AUTHOR]