The prognostic role of galectin-3 and endothelial function in patients with heart failure

Background: Heart failure (HF) is nowadays classified as HF with reduced ejection fraction (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF). Endothelial dysfunction (assessed by flow-mediated dilatation [FMD]), increased arterial stiffness (assessed by carotid-femoral pulse-wave velocity [PWV]), and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF. Methods: In this study we prospectively enrolled 340 patients with stable ischemic HF. We assessed the brachial artery FMD, carotid-femoral PWV, and galectin-3 levels, and patients were followed up for MACE according to EF group. Results: Interestingly, the FMD values exhibited a stepwise improvement according to left ventricular ejection fraction (LVEF) (HFrEF: 4.74 ± 2.35% vs. HFmrEF: 4.97 ± 2.81% vs. HFpEF: 5.94 ± 3.46%, p = 0.01), which remained significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors, and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% confidence interval: 0.166–1.814, p = 0.019). Single-vessel coronary artery disease (CAD) was more frequent in the group of HFpEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p = 0.049). PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51 ± 2.35% vs. 5.32 ± 2.67%, p = 0.02), and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p = 0.01). Conclusions: Flow-mediated dilatation displayed a linear improvement with LVEF in patients with ischemic HF. Deteriorated values are associated with MACE. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF

Η εκτίμηση της λειτουργίας του ενδοθηλίου, της ελαστικότητας των μεγάλων αρτηριών και της φλεγμονής σε ασθενείς με διαβητική αμφιβληστροειδοπάθεια

Εισαγωγή: Ο σακχαρώδης διαβήτης (ΣΔ) σχετίζεται με ενδοθηλιακή δυσλειτουργία, αυξημένη αρτηριακή σκληρία και χρόνια συστηματική φλεγμονή, που παίζουν καίριο ρόλο στην ανάπτυξη διαβητικών μακροαγγειακών επιπλοκών. Η διαβητική αμφιβληστροειδοπάθεια (ΔΑ), μία από τις σημαντικότερες διαβητικές μικροαγγειακές επιπλοκές, συνιστά την κύρια αιτία μη αναστρέψιμης τύφλωσης στο δυτικό κόσμο. Σκοπός: Η αναγνώριση νέων παραγόντων κινδύνου για την ανάπτυξη της ΔΑ είναι αναγκαία, καθώς η παθογένεση της ΔΑ έχει εν μέρει μόνο εξηγηθεί. Στη μελέτη μας ερευνήσαμε τις πιθανές συσχετίσεις της ΔΑ με την ενδοθηλιακή λειτουργία, την αρτηριακή δυσκαμψία και τη φλεγμονή, καθώς και πώς τα πιθανά ευρήματα θα μπορούσαν να χρησιμοποιηθούν για την έγκαιρη αναγνώριση και την παρακολούθηση των υψηλού κινδύνου ασθενών για ανάπτυξη ΔΑ. Μέθοδοι: Συμμετείχαν 200 ασθενείς με ΣΔ τύπου 2 (ΣΔ-2) και 100 υγιείς-μάρτυρες (μέσης ηλικίας 63±11 ετών). Με βάση την οφθαλμολογική εξέταση, οι ασθενείς χωρίστηκαν στους διαβητικούς χωρίς ΔΑ (108 άτομα, μέσης ηλικίας 64±10 ετών) και στους ασθενείς με ΔΑ (92 άτομα, μέσης ηλικίας 69±9 ετών), οι οποίοι χωρίστηκαν περαιτέρω στους ασθενείς με ΔΑ υποστρώματος (78 άτομα, μέσης ηλικίας 69±8 ετών) και με παραγωγική ΔΑ (14 άτομα, μέσης ηλικίας 70±12 ετών). Η ενδοθηλιακή λειτουργία εκτιμήθηκε με τον προσδιορισμό της ενδοθηλιοεξαρτώμενης αγγειοδιαστολής (FMD) στη βραχιόνιο αρτηρία, η καρωτιδο-μηριαία ταχύτητα σφυγμικού κύματος (PWV) υπολογίστηκε ως δείκτης αρτηριακής σκληρίας, ενώ υπολογίστηκε και o δείκτης ενίσχυσης των ανακλώμενων κυμάτων (AIx). Ο λόγος FMD/PWV υπολογίστηκε ως ένας σύνθετος βιοδείκτης εκτίμησης της αγγειακής λειτουργίας. Τα επίπεδα στον ορό της hsCRP και του ICAM-1 μετρήθηκαν ως δείκτες συστηματικής φλεγμονής. Επίσης καταγράφηκαν διάφορα δημογραφικά χαρακτηριστικά των συμμετεχόντων, καθώς και πολλαπλοί βιοχημικοί δείκτες, συμπεριλαμβανομένης της γλυκοζυλιωμένης αιμοσφαιρίνης (HbA1c). Τέλος, 73 από τους ασθενείς χωρίς ΔΑ επανεξετάστηκαν μετά από 30 μήνες για την ανάπτυξη ΔΑ. Αποτελέσματα: Οι ασθενείς με ΔΑ συγκρινόμενοι με τους ασθενείς χωρίς ΔΑ και τους υγιείς-μάρτυρες είχαν διαταραγμένες τιμές FMD, PWV και AIx και χαμηλότερο λόγο FMD/PWV (p<0.001 για όλα), ακόμη και μετά από προσαρμογή για πολλαπλούς συγχυτικούς παράγοντες. Οι ασθενείς με ΔΑ σε σύγκριση με τους ασθενείς χωρίς ΔΑ ήταν μεγαλύτεροι, είχαν εμφανίσει νωρίτερα και έπασχαν περισσότερα χρόνια από ΣΔ, είχαν χειρότερη ρύθμιση σακχάρου, σημαντικά μειωμένες τιμές FMD και FMD/PWV και αυξημένες τιμές PWV (p<0.05 για όλα), ενώ δεν ανιχνεύθηκαν διαφορές για τους φλεγμονώδεις δείκτες. Μεταξύ των διαβητικών, οι τιμές των FMD και FMD/PWV είχαν επαρκή διακριτική ικανότητα για τη ΔΑ, με την αρνητική προγνωστική αξία μιας τιμής FMD άνω του 4,36% για την παρουσία ΔΑ να ανέρχεται στο 85%. Δεν υπήρχαν διαφορές για οποιονδήποτε βιοδείκτη αγγειακής λειτουργίας μεταξύ των ασθενών με ΔΑ παραγωγική και υποστρώματος. Ο επανέλεγχος αποκάλυψε την ανάπτυξη ΔΑ σε 15 άτομα. Στην υποομάδα ασθενών χωρίς ΔΑ κατά την έναρξη της μελέτης, οι οι ασθενείς με νέα ΔΑ, σε σύγκριση με εκείνους που δεν ανέπτυξαν ΔΑ, είχαν υψηλότερα αρχικά επίπεδα HbA1c, μεγαλύτερη διάρκεια ΣΔ και πρωιμότερη εμφάνιση της νόσου. Οι ασθενείς με νέα ΔΑ εμφάνισαν επίσης επιδείνωση του γλυκαιμικού ελέγχου και του σωματικού τους βάρους. Τέλος, ο σύνθετος δείκτης FMD/PWV ήταν σημαντικά χαμηλότερος σε όσους ανέπτυξαν ΔΑ. Συμπεράσματα: Η μελέτη μας έδειξε ότι η ΔΑ σχετίζεται με ενδοθηλιακή και αρτηριακή δυσλειτουργία και αυξημένη αρτηριακή δυσκαμψία. Αυτά τα ευρήματα τονίζουν τη σημασία της παρακολούθησης της ενδοθηλιακής λειτουργίας και της αρτηριακής ελαστικότητας σε ασθενείς με ΣΔ για την αποφυγή μη αναστρέψιμων μικροαγγειακών επιπλοκών, ενώ παρέχουν περαιτέρω παθοφυσιολογικές συνδέσεις σχετικά με τη συσχέτιση της ενδοθηλιακής δυσλειτουργίας και της βλάβης του αρτηριακού τοιχώματος με διαβητικές επιπλοκές, που μπορούν να χρησιμοποιηθούν για το σχεδιασμό νέων θεραπειών στη ΔΑ. Η επανεξέταση κατέδειξε το σημαντικό ρόλο του αυστηρού γλυκαιμικού ελέγχου και της διαχείρισης του βάρους στην πρόληψη της εμφάνισης της μικροαγγειακής νόσου σε ασθενείς με ΣΔ-2. Τέλος, αναγνωρίστηκε ο μειωμένος λόγος FMD/PWV ως ένας πιθανός νέος βιοδείκτης, ο οποίος είναι σε θέση να αναγνωρίσει τους διαβητικούς ασθενείς που διατρέχουν υψηλό κίνδυνο ανάπτυξης ΔΑ.Background: Diabetes mellitus (DM) is associated with impaired endothelial function, increased arterial stiffness and a state of chronic low-level systemic inflammation. All of them play a key role in the development of diabetic macrovascular complications. Diabetic retinopathy (DR) remains one of the most significant diabetic microvascular complications and a leading cause of irreversible blindness in the western world. Purpose: Identification of new risk factors for DR development is needed, since DR pathogenesis is only partially explained. In this study, we investigated the possible associations of DR with endothelial function, arterial stiffness and inflammation, and how these measurements could be used for the early recognition and monitoring of patients at high risk to develop DR. Methods: We enrolled 200 consecutive subjects with type-2 DM (T2DM) and 100 healthy-control (CL) subjects (mean age 63±11y). According to the ophthalmological examination, patients were divided in those with no evidence of DR (NDR) (108 subjects, mean age 64±10y) and in those with DR (92 subjects, mean age 69±9y), who were further divided to Background DR (BDR) (78 subjects, mean age 69±8y) and Proliferative DR (PDR) (14 subjects, mean age 70±12y). Endothelial function was assessed by Flow Mediated Dilation (FMD) in the brachial artery, carotid-femoral Pulse Wave Velocity (PWV) evaluated arterial stiffness, while Augmentation Index (AIx) of the radial artery evaluated arterial stiffness and reflected waves. FMD/PWV ratio was calculated as a composite risk biomarker of vascular function. Serum levels of hsCRP and ICAM-1 were measured as markers of systemic inflammation. Several demographic and biochemical characteristics, including HbA1c, were also estimated. Finally, 73 of the NDR patients at baseline were re-examined after 30 months for DR progression. Results: DR compared to NDR patients and CL subjects had impaired FMD, PWV and AIx values and lower FMD/PWV ratio (p<0.001 for all), even after adjustment for multiple confounders. DR compared to NDR patients were older, had longer duration and earlier onset of DM, poorer glycemic control, significantly impaired values of FMD, PWV and FMD/PWV (p<0.05 for all), whereas no differences were detected for inflammatory markers. Among DM subjects, FMD and FMD/PWV had sufficient discriminate ability to detect DR and the negative predictive value of an FMD above 4.36% for the presence of DR was estimated at 85%. No differences existed for any vascular function biomarker between BDR and PDR patients. During follow-up 15 patients developed DR (DR Progressors). In the subgroup of patients free of DR at baseline, DR Progressors, compared to those that did not develop DR (NoDR), had higher baseline HbA1c levels, longer DM duration and earlier disease onset. DR progressors had also adverse changes in glycemic control and weight management. Furthermore, the composite index of FMD/PWV was significantly lower in DR Progressors compared to NoDR group. Conclusions: Our study showed that DR is associated with impaired endothelial and arterial function and increased arterial stiffness. These findings highlight the importance of monitoring endothelial function and arterial stiffness in DM patients to avert irreversible microvascular complications, and provide further pathophysiological connections concerning the association of endothelial dysfunction and arterial wall impairment with DM complications, which can be used to design new treatment in cases of DR. Follow-up examination demonstrated the significant role of strict glycemic control and weight management in preventing microvascular disease progression in T2DM patients. Finally, we identified decreased FMD/PWV ratio as a possible novel biomarker which is able to identify DM patients at high risk for DR development

Optic disk melanocytoma associated with polypoidal choroidal vasculopathy lesions, after combination treatment of photodynamic therapy and intavitreal aflibercept (Eylea), a case report

Abstract Background We report a rare case of a woman with optic disk melanocytoma (ODMC) in conjunction with polypoidal choroidal vasculopathy (PCV). We also present, for the first time in literature, the clinical and morphological outcomes of the applied treatment, consisting of a session of photodynamic therapy (PDT) and three monthly intravitreal aflibercept injections. Case presentation An 83-year-old Greek woman, complaining for visual decline at her left eye, referred to our department and was diagnosed with ODMC associated with PCV. At presentation, best corrected visual acuity (BCVA) was 2/10, fundus examination revealed a pigmented lesion covering partially the optic nerve head and extending into the peripapillary choroid and retina, while hard exudates were observed temporal to it. Blocked hypofluorescence in the area covered by the lesion and diffuse hyperfluorescence at its temporal rim were shown by fluorescein angiography (FA). Indocyanine green angiography (ICGA) identified 3 hyperfluorescent polypoidal lesions arising from the choroidal vasculature. Optical coherence tomography (OCT) revealed subretinal fluid and retinal pigment epithelium detachment (RPE) at the region corresponding to polyps. The treatment included a PDT session combined with 3 monthly intravitreal aflibercept injections. Three months since the treatment initiation, new BCVA was 5/10, ICGA demonstrated total polyps occlusion, while OCT detected RPE detachment without subretinal fluid. Ten months later, ODMC was stable, BCVA rose to 7/10, no polyps were present, and total resolution of RPE detachment was achieved. Conclusions This is the first case report of PCV coexisting with ODMC, presenting both ICGA and OCT findings, and the applied treatment and its outcomes. Furthermore, we demonstrated that PDT combined with intravitreal aflibercept injections seems to be a promising treatment for PCV

One-year outcomes of resveratrol supplement with aflibercept versus aflibercept monotherapy in wet age-related macular degeneration

AIM: To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration (AMD). METHODS: Fifty naïve and previously untreated patients suffering from wet AMD, were randomly assigned in two subgroups of 25 patients each. All the participants were treated with 3 monthly intravitreal injections of 2.0 mg aflibercept (IAIs) followed by injections “according to need”, while in one group the patients also received daily two tablets of resveratrol oral supplement. Prior to treatment initiation, a complete ophthalmological examination, including best corrected visual acuity (BCVA) and contrast sensitivity evaluation, optical coherence tomography (OCT) scans, fundus autofluorescence (FAF), fluorescein angiography, indocyanine green angiography, and OCT angiography (OCTA), was performed to every participant, while all of them completed the Hospital Anxiety and Depression Scale (HADS) questionnaire, in order to assess their quality of life (QoL) status. The patients were assessed monthly for 1y with FAF, and OCT or OCTA; the main endpoints were the number IAIs, the changes in BCVA, in contrast sensitivity, and in patients' QoL status. RESULTS: No significant differences were present between the groups regarding the baseline demographic and clinical data. Over the 12-month period, a similar number of IAIs was applied in both groups (4.52±1.00 vs 4.28±0.90, P=0.38), while the rest of the clinical data also did not differ significantly after the completion of the study period. However, for HADS Depression (11.88±2.51 vs 8.28±1.54, P<0.001) and HADS Anxiety (11.92±2.52 vs 7.76±1.51, P<0.001) questionnaires values, the score was significantly better in patients who received resveratrol supplements. Moreover, a statistically significant difference was detected in the mean change from baseline values of contrast sensitivity (0.17±0.19 vs 0.35±0.24, P=0.005), HADS Depression (0.08±1.38 vs -3.88±1.48, P<0.001), and HADS Anxiety (0.36±1.98 vs -5.12±2.70, P<0.001) scores, in favour of the patients treated with resveratrol supplements. CONCLUSION: The resveratrol oral supplement is a complementary treatment in cases of wet AMD, highlighting its effectiveness in improving patients' QoL status

One year outcomes of treat and extend and pro re nata (PRN) treatment regimens with aflibercept for polypoidal choroidal vasculopathy

Purpose: To compare the 1-year outcomes of treat-and-extend and pro re nata (PRN) treatment regimens with aflibercept for polypoidal choroidal vasculopathy (PCV), by the means of visual acuity (VA), frequency of recurrence of polypoidal lesions and developed fibrosis, and the number of intravitreal injections, and thus to determine which one is preferable in the maintenance phase in PCV. Methods: In our prospective study, only naive and previously untreated PCV patients were included. Initially one session of photodynamic therapy (PDT) and three monthly intravitreal injections of 2.0 mg aflibercept (IAIs) were applied in 38 eyes. After this loading phase, they were re-examined and 30 PCV eyes with no exudative phenomena were included in the study. They were divided in two groups; in the first one (16 patients) the PRN treatment modality of IAIs was applied, while in the second one (14 patients) the treat-and-extend regimen was applied. Results: Over a 12-month period, VA significantly improved in treat-and-extend group (logMAR BCVA 0.41 +/- 0.15 vs 0.57 +/- 0.24 at baseline, p = 0.044), while in the PRN group VA remained stable (logMAR BCVA 0.70 +/- 0.36 vs 0.65 +/- 0.18 at baseline, p = 0.61). During the maintenance phase, the patients of treat-and-extend group did not encounter development/progression of fibrosis or any recurrent episodes, whereas the patients of PRN group had significantly more recurrent episodes (0 vs 1.37 +/- 0.5, p &lt; 0.001) and the frequency of development/progression of fibrosis was significantly higher (0% vs 44%, p = 0.02). However, the treat-and-extend treatment regimen was accompanied by significantly more administered IAIs (6 +/- 0 vs 5.13 +/- 1.08, p = 0.006). Conclusion: We highlighted the superiority of treat-and-extend regime with IAIs, which seems to yield better functional outcomes by preventing recurrence and subfoveal fibrosis, although a greater number of injections is required

Polymorphism analysis of miR182 and CDKN2B genes in Greek patients with primary open angle glaucoma.

Glaucoma is a progressive optic neuropathy resulting from retinal ganglion cells death; it represents one of the leading causes of irreversible blindness worldwide. Although, primary open angle glaucoma (POAG) is the most common type of the disease, the pathogenesis of POAG and the genetic factors contributing to disease development remain poorly understood. The aim of this study was to investigate whether the polymorphisms rs76481776 in miR182 gene and rs3217992 in cyclin-dependent kinase inhibitor-2B (CDKN2B) gene are risk factors for POAG in a series of patients of Greek origin. A case-control study was conducted including 120 patients with POAG and 113 unaffected healthy controls of Greek origin, surveyed for polymorphisms with potential correlation to POAG. DNA from each individual was tested for the miR182 rs76481776 and CDKN2B rs3217992 polymorphisms. Regarding the miR182 rs76481776 polymorphism, the T allele occurred with significantly higher frequency in POAG patients compared to controls (OR: 2.62, 95% CI: 1.56-4.39; p = 0.0002). The CDKN2B rs3217992 A allele frequency was found significantly increased in POAG patients compared to healthy individuals (OR: 1.72, 95% CI: 1.18-2.49; p = 0.005). Therefore, both rs76481776 polymorphism in miR182 gene and rs3217992 polymorphism in CDKN2B gene seem to be associated with the development of POAG in a Greek population. The carriers of the T allele of rs76481776 in miR182 and the carriers of the A allele of rs3217992 in CDKN2B have an increased risk of developing POAG

Psychological aspects and depression in patients with symptomatic keratoconus

Purpose. To assess the psychological status of keratoconus sufferers and to determine the relationship between depression and visual impairment in this group of patients. Methods. Fifty-six patients with keratoconus and forty-seven age- and gender-matched healthy control subjects were retroprospectively analyzed. Every participant underwent a complete ophthalmological examination. Keratoconus diagnosis was confirmed with corneal topography and tomography. Zung Depression Inventory Questionnaire and Patient Health Questionnaire-9 (PHQ-9) were completed by everyone. Results. Visual acuity (logMAR 0.53 +/- 0.30 versus 0.11 +/- 0.16), PHQ-9 score (10.20 +/- 4.00 versus 5.40 +/- 5.01), and Zung score (46.52 +/- 8.70 versus 38.53 +/- 8.41) showed a statistically significant difference between keratoconus patients and healthy controls (p &lt; 0.001 for all). Worse visual acuity was strongly correlated with older individuals (rho = 0.339, p = 0.011) and higher PHQ-9 (rho = 0.765, p &lt; 0.001) and Zung score (rho = 0.672, p &lt; 0.001). Conclusion. Depressive disorders appear to be directly associated with keratoconus, both in frequency and intensity. Worse visual acuity and older age could be identified as predictive factors for their emotional status. Moreover, the disease itself could be recognized as an independent risk factor for depression development, underlying the need for close monitoring and supportive management. To the best of our knowledge, our study is the first in the literature to elaborate the association between keratoconus and depression, by assessing two different questionnaires simultaneously