Vascular Retinopathies Research Articles

Abstract 2133 Spatially biased atypical p38 signaling as a critical regulator of vascular retinopathies

Abstract 2133 Spatially biased atypical p38 signaling as a critical regulator of vascular retinopathies

Benign masquerade syndromes ‐ An overview

Uveitis are complex diseases with often a difficult diagnosis and management. Other conditions can mimic uveitis. Among those there are also benign (no malignant) conditions such as inherited retinal diseases or vascular retinopathies. The aim of this talks is to provide an overview of the different benign conditions that we need to know to properly diagnose and treat uveitis.

Exploring the Potential of Wild Olive (Acebuche) Oil as a Pharm-Food to Prevent Ocular Hypertension and Fibrotic Events in the Retina of Hypertensive Mice.

Our laboratoryhas previously described the antioxidant and anti-inflammatory potential of a wild olive (acebuche, ACE) oil against hypertension-associated vascular retinopathies. The current study aims to analyze the antifibrotic effect of ACE oil on the retina of hypertensive mice. Mice are rendered hypertensive by administration of NG-nitro-L-arginine-methyl-ester (L-NAME) and simultaneously subjected to dietary supplementation with ACE oil or a reference extra virgin olive oil (EVOO). Intraocular pressure (IOP) is measured by rebound tonometry, and retinal vasculature/layers are analyzed by fundus fluorescein angiography and optical coherence tomography. Different fibrosis-related parameters are analyzed in the retina and choroid of normotensive and hypertensive mice with or without oil supplementation. Besides preventing the alterations found in hypertensive animals, including increased IOP, reduced fluorescein signal, and altered retinal layer thickness, the ACE oil-enriched diet improves collagen metabolism by regulating the expression of major fibrotic process modulators (matrix metalloproteinases, tissue inhibitors of metalloproteinases, connective tissue growth factor, and transforming growth factor beta family). Regular consumption of EVOO and ACE oil (with better outcomes in the latter) might help reduce abnormally high IOP values in the context of hypertension-related retinal damage, with significant reduction in the surrounding fibrotic process.

Polytherapy and Multimorbidity Pattern of Users of Anti-VEGF Drugs and Dexamethasone for the Treatment of Age-Related Macular Degeneration and other Vascular Retinopathies in Clinical Practice.

Introduction: Our aim was to describe the polytherapy and multimorbidity pattern of users of anti-VEGF and dexamethasone drugs for the treatment of these conditions, and to investigate their polytherapy and multimorbidity profiles, together with adherence and the burden of care. Methods: Descriptive, population-based, pharmacoepidemiology study on the users of anti-VEGF drugs, and secondarily intravitreal dexamethasone, for the treatment of age-related macular degeneration and other vascular retinopathies in clinical practice, using administrative databases of Lazio region, Italy. We used a cohort of 50,000 residents in Lazio in 2019 with same age as comparison. Polytherapy was assessed using databases of prescribed drugs intended for outpatient use. Multimorbidity was investigated with additional sources, such as hospital discharge records, outpatient care records, and disease-specific exemptions from co-payment. Each patient was followed for 1 to 3 years from the first intravitreal injection received. Results: 16,266 residents in Lazio who received the first IVI from 1 January 2011 to 31 December 2019, with at least 1 year of observation before index date, were included. The proportion of patients with at least one comorbidity was 54.0%. Patients used an average 8.6 (SD 5.3) concomitant drugs other than anti-VEGF used for injections. A large percentage of patients (39.0%) used 10 or more concomitant drugs, including antibacterials (62.9%), drugs for peptic ulcers (56.8%), anti-thrombotics (52.3%), NSAIDs (44.0%), and anti-dyslipidaemics (42.3%). The same proportions were found across patients of all ages, probably due to high prevalence of diabetes (34.3%), especially in younger age groups. When stratified by diabetes, a comparison of multimorbidity and polytherapy with a sample of 50,000 residents of the same age found that patients receiving IVIs used more drugs and had more comorbidities, particularly in non-diabetics. Lapses of care, whether short (absence of any type of contact for at least 60 days in the first year of follow-up and 90 in the second year) or long (90 days in the first and 180 days in the second year) were common: 66% and 51.7%, respectively. Conclusions: Patients receiving intravitreal drugs for retinal conditions have high multimorbidity and polytherapy rates. Their burden of care is aggravated by the large number of contacts with the eye care system for examinations and injections. Pursuing Minimally Disruptive Medicine to optimise patient care is a difficult goal for health systems, and more research on clinical pathways and their implementation is warranted.

Deep Learning in Optical Coherence Tomography Angiography: Current Progress, Challenges, and Future Directions.

Optical coherence tomography angiography (OCT-A) provides depth-resolved visualization of the retinal microvasculature without intravenous dye injection. It facilitates investigations of various retinal vascular diseases and glaucoma by assessment of qualitative and quantitative microvascular changes in the different retinal layers and radial peripapillary layer non-invasively, individually, and efficiently. Deep learning (DL), a subset of artificial intelligence (AI) based on deep neural networks, has been applied in OCT-A image analysis in recent years and achieved good performance for different tasks, such as image quality control, segmentation, and classification. DL technologies have further facilitated the potential implementation of OCT-A in eye clinics in an automated and efficient manner and enhanced its clinical values for detecting and evaluating various vascular retinopathies. Nevertheless, the deployment of this combination in real-world clinics is still in the "proof-of-concept" stage due to several limitations, such as small training sample size, lack of standardized data preprocessing, insufficient testing in external datasets, and absence of standardized results interpretation. In this review, we introduce the existing applications of DL in OCT-A, summarize the potential challenges of the clinical deployment, and discuss future research directions.

The Role of Widefield and Ultra Widefield Optical Coherence Tomography in the Diagnosis and Management of Vitreoretinal Diseases.

Background: This study reports on the advantages of wide-field (WF)- and ultra-widefield (UWF)- optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in managing different vitreoretinal diseases in a real-life setting using the new WF—Swept Source (SS)—OCT Xephilio S1 (Canon, Tokyo, Japan). Methods: We conducted an observational retrospective case series study involving 1472 eyes that underwent retinal scans with Canon Xephilio® OCT-S1 between 1 March 2021 and 1 December 2021 at Eyecare Clinic (Brescia, Italy). All patients underwent routine ophthalmologic examinations along with WF and UWF color fundus retinography with Clarus 500™ (Carl Zeiss Meditec, Inc., Dublin, CA, USA) and Xephilio® OCT-S1. WF SS-OCT, UWF-OCT, WF-OCTA, and UWF-OCTA were taken by using Xephilio® OCT-S1. Results: We analyzed 122 peripheral retinal lesions, 144 retinal detachment, 329 high myopic eyes, 37 pediatric cases, 60 vascular retinopathies, 15 choroidal lesions, and 90 eyes as follow-up post vitreoretinal surgery. The OCT-S1 was the only reliable and diagnostic exam for peripheral lesions, pediatric and high myopic cases, and significantly influenced the management in 10% of cases and the postoperative follow-up. Conclusions: WF and UWF OCT and OCTA imaging may help in the management of several vitreoretinal diseases, becoming an indispensable tool for the high-quality management of patients.

Metabolism and Vascular Retinopathies: Current Perspectives and Future Directions.

The retina is one of the most metabolically active organs in the body. Although it is an extension of the brain, the metabolic needs of the retina and metabolic exchanges between the different cell types in the retina are not the same as that of the brain. Retinal photoreceptors convert most of the glucose into lactate via aerobic glycolysis which takes place in their cytosol, yet there are immense numbers of mitochondria in photoreceptors. The present article is a focused review of the metabolic dysregulation seen in retinopathies with underlying vascular abnormalities with aberrant mitochondrial metabolism and Hypoxia-inducible factor (HIF) dependent pathogenesis. Special emphasis has been paid to metabolic exchanges between different cell types in retinopathy of prematurity (ROP), age-related macular degeneration (AMD), and diabetic retinopathy (DR). Metabolic similarities between these proliferative retinopathies have been discussed.

A systematic review of cases of West African crystalline maculopathy.

West African crystalline maculopathy (WACM) is, reportedly, a rare condition whose aetiology remains unclear. This study aims to describe the epidemiology, summarizing the identified risk factors and clinical characteristics of cases of WACM, with the goal of highlighting presentation patterns and the clinical course of the condition. A comprehensive PubMed, Medline, EMBASE, Web of Science, OMIM and Google scholar search of all articles written in English, and non-English language articles with abstract translated to English on WACM was carried out. Only full case reports and series were included. Data reviewed included epidemiology, risk factors, clinical presentations, imaging characteristics, management and prognosis of WACM. Information on the location of the study was also extracted. Ten studies - seven case reports and three case series - comprising of 30 patients were included. The patients were from West, Central and North-east Africa, with all the studies carried out in North America and Europe. The majority of the patients (76.7%) had diabetes mellitus, 80% had a vascular retinopathy (diabetic retinopathy, sickle cell retinopathy, familial exudative vitreoretinopathy and branch retinal vein occlusion) and 50% had macular oedema. There was no report of associated visual impairment or retinal degeneration. Clinical improvement in the number of crystals was documented in two cases with retinal laser photocoagulation for associated vascular retinopathies. Clinical observation was employed by most clinicians. West African crystalline retinopathy is a seemingly innocuous condition affecting black or African people, who were also born in Africa. The majority of the patients have a vascular retinopathy. Longitudinal studies, particularly in Africa, may be required to elucidate the aetiology, as well as the long-term prognosis, of the crystals.

Anti-Inflammatory Action of Dietary Wild Olive (Acebuche) Oil in the Retina of Hypertensive Mice.

Inflammation plays a crucial role in the course of eye diseases, including many vascular retinopathies. Although olive oil is known to have beneficial effects against inflammatory processes, there is no information available on the anti-inflammatory potential of the wild olive tree (namely, acebuche (ACE) for the primitive Spanish lineages). Here we investigate the anti-inflammatory effects of ACE oil in the retina of a mouse model of arterial hypertension, which was experimentally induced by administration of L-NAME (NG-nitro-L-arginine-methyl-ester). The animals were fed supplements of ACE oil or extra virgin olive oil (EVOO, for comparative purposes). Retinal function was assessed by electroretinography (ERG), and different inflammation-related parameters were measured in the retina and choroid. Besides significant prevention of retinal dysfunction shown in ERG recordings, ACE oil-enriched diet upregulated the expression of the anti-inflammatory markers PPARγ, PPARα and IL-10, while reducing that of major proinflammatory biomarkers, IL-1β, IL-6, TNF-α and COX-2. This is the first report to highlight the anti-inflammatory properties of an ACE oil-enriched diet against hypertension-related retinal damage. Noteworthy, dietary supplementation with ACE oil yielded better results compared to a reference EVOO.

Spectral Domain Optical Coherence Tomography in Retinal Vasculopathy With Cerebral Leukoencephalopathy and Systemic Manifestations: A Monogenic Small Vessel Disease.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a monogenic small vessel disease caused by mutations in TREX1. Several organs, including retina and brain, are affected. Analyzing retinal anatomy is increasingly used as a biomarker for ophthalmological and neurological disorders (due to the shared embryological origin of retina and brain). Optical coherence tomography (OCT) provides a noninvasive cross-sectional visualization of optic disc and macula. We aimed to use OCT to investigate retinal layer thickness in RVCL-S. Cross-sectional, 17 TREX1 mutation carriers (34 eyes) and 9 controls (18 eyes) underwent comprehensive ophthalmologic assessment followed by spectral domain OCT for measuring peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular volume (TMV). Secondary outcomes included measuring thickness of individual macular retinal layers and peripapillary sectors. Findings were analyzed using generalized estimating equations to account for intereye correlation. TREX1 mutation carriers had decreased pRNFL thickness (median [interquartile range] 76 [60-99] vs 99 [87-108] µm, P < 0.001) and TMV (8.1 [7.4-8.5] vs 8.7 [8.4-8.8] mm3, P = 0.006) compared with controls. With the exception of the temporal sector, the thickness of all peripapillary sectors was decreased in TREX1 mutation carriers. Ganglion cell layer (30 [22-37] vs 39 [36-41] µm, P < 0.001) and inner plexiform layer (27 [24-34] vs 34 [31-35], P = 0.001) were thinner in TREX1 mutation carriers. Notably, in 9 of 12 eyes with normal funduscopic examination, retinal thinning was already detected. RVCL-S, which may serve as a vascular retinopathy model, is associated with retinal thinning in the peripapillary and macular area. OCT findings can potentially serve as early biomarkers for RVCL-S and other vascular retinopathies.

A new deep learning method for blood vessel segmentation in retinal images based on convolutional kernels and modified U-Net model

Background and Objective: Automatic monitoring of retinal blood vessels proves very useful for the clinical assessment of ocular vascular anomalies or retinopathies. This paper presents an efficient and accurate deep learning-based method for vessel segmentation in eye fundus images.Methods: The approach consists of a convolutional neural network based on a simplified version of the U-Net architecture that combines residual blocks and batch normalization in the up- and downscaling phases. The network receives patches extracted from the original image as input and is trained with a novel loss function that considers the distance of each pixel to the vascular tree. At its output, it generates the probability of each pixel of the input patch belonging to the vascular structure. The application of the network to the patches in which a retinal image can be divided allows obtaining the pixel-wise probability map of the complete image. This probability map is then binarized with a certain threshold to generate the blood vessel segmentation provided by the method.Results: The method has been developed and evaluated in the DRIVE, STARE and CHASE_Db1 databases, which offer a manual segmentation of the vascular tree by each of its images. Using this set of images as ground truth, the accuracy of the vessel segmentations obtained for an operating point proposal (established by a single threshold value for each database) was quantified. The overall performance was measured using the area of its receiver operating characteristic curve. The method demonstrated robustness in the face of the variability of the fundus images of diverse origin, being capable of working with the highest level of accuracy in the entire set of possible points of operation, compared to those provided by the most accurate methods found in literature.Conclusions: The analysis of results concludes that the proposed method reaches better performance than the rest of state-of-art methods and can be considered the most promising for integration into a real tool for vascular structure segmentation.

Imaging the pediatric retina: An overview.

Recent decade has seen a shift in the causes of childhood blinding diseases from anterior segment to retinal disease in both developed and developing countries. The common retinal disorders are retinopathy of prematurity and vitreoretinal infections in neonates, congenital anomalies in infants, and vascular retinopathies including type 1 diabetes, tumors, and inherited retinal diseases in children (up to 12 years). Retinal imaging helps in diagnosis, management, follow up and prognostication in all these disorders. These imaging modalities include fundus photography, fluorescein angiography, ultrasonography, retinal vascular and structural studies, and electrodiagnosis. Over the decades there has been tremendous advances both in design (compact, multifunctional, tele-consult capable) and technology (wide- and ultra-wide field and noninvasive retinal angiography). These new advances have application in most of the pediatric retinal diseases though at most times the designs of new devices have remained confined to use in adults. Poor patient cooperation and insufficient attention span in children demand careful crafting of the devices. The newer attempts of hand-held retinal diagnostic devices are welcome additions in this direction. While much has been done, there is still much to do in the coming years. One of the compelling and immediate needs is the pediatric version of optical coherence tomography angiography. These needs and demands would increase many folds in future. A sound policy could be the simultaneous development of adult and pediatric version of all ophthalmic diagnostic devices, coupled with capacity building of trained medical personnel.

The Role of Inflammation in Diabetic Retinopathy.

Inflammation is central to pathogenic processes in diabetes mellitus and the metabolic syndrome and particularly implicates innate immunity in the development of complications. Inflammation is a primary event in Type 1 diabetes where infectious (viral) and/or autoimmune processes initiate disease; in contrast, chronic inflammation is typical in Type 2 diabetes and is considered a sequel to increasing insulin resistance and disturbed glucose metabolism. Diabetic retinopathy (DR) is perceived as a vascular and neurodegenerative disease which occurs after some years of poorly controlled diabetes. However, many of the clinical features of DR are late events and reflect the nature of the retinal architecture and its cellular composition. Retinal microvascular disease is, in fact, an early event pathogenetically, induced by low grade, persistent leukocyte activation which causes repeated episodes of capillary occlusion and, progressive, attritional retinal ischemia. The later, overt clinical signs of DR are a consequence of the retinal ischemia. Metabolic dysregulation involving both lipid and glucose metabolism may lead to leukocyte activation. On a molecular level, we have shown that macrophage-restricted protein tyrosine phosphatase 1B (PTP1B) is a key regulator of inflammation in the metabolic syndrome involving insulin resistance and it is possible that PTP1B dysregulation may underlie retinal microvascular disease. We have also shown that adherent CCR5+CD11b+ monocyte macrophages appear to be selectively involved in retinal microvascular occlusion. In this review, we discuss the relationship between early leukocyte activation and the later features of DR, common pathogenetic processes between diabetic microvascular disease and other vascular retinopathies, the mechanisms whereby leukocyte activation is induced in hyperglycemia and dyslipidemia, the signaling mechanisms involved in diabetic microvascular disease, and possible interventions which may prevent these retinopathies. We also address a possible role for adaptive immunity in DR. Although significant improvements in treatment of DR have been made with intravitreal anti-VEGF therapy, a sizeable proportion of patients, particularly with sight-threatening macular edema, fail to respond. Alternative therapies targeting inflammatory processes may offer an advantage.

Protective effects of hypercapnic acidosis on Ischemia-reperfusion-induced retinal injury.

Ischemia–reperfusion (I/R) injury is associated with numerous retinal diseases, such as diabetic retinopathy, acute glaucoma, and other vascular retinopathies. Hypercapnic acidosis (HCA) has a protective effect on lung, myocardial, and central nervous system ischemic injury models. However, no study has evaluated its protective effects in an experimental retinal I/R injury model. In this study, retinal I/R injury was induced in Sprague Dawley rats by elevating the intraocular pressure to 110 mmHg for 60 minutes. HCA was induced before and after the injury. After 24 hours, the terminal dUTP nick end labeling assay was performed. Moreover, the ratios of cleaved caspase-3/total caspase-3, phosphorylated IκB/IκB, and phosphorylated p38 were measured through Western blotting. After 7 days, the rats’ aqueous humor was analyzed. In addition, electroretinography and retinal thickness measurement were performed in the rats. Moreover, the retinal neural cell line RGC-5 was exposed to 500 μM H2O2 for 24 hours to induce a sustained oxidative stress in vitro. The effects of HCA were evaluated by comparing oxidative stress, MAPK signals, NF-κB signals, survival rates, and apoptosis rates in the RGC-5 cells before and after H2O2 exposure. We further investigated whether the potent I/R-protective heat shock protein (HSP) 32 contribute to protective effects of HCA. Our results indicated that HCA has protective effects against retinal I/R injury both in vivo and in vitro, at multiple levels, including antiapoptotic, anti-inflammatory, antioxidative, and functional retinal cell protection. Further research clarifying the role of HCA in retinal I/R injury prevention and treatment is warranted.

Early isolated optic neuropathy caused by cyclosporine.

To examine, for the first time, whether cyclosporine intake has an early isolated effect on the optic nerve. This observational case series consisted of 192 eyes of 98 patients treated with cyclosporine. Patient age and duration and dosage of cyclosporine were recorded, and visual acuity, optic nerve function, visual fields, and visual evoked potential (VEP) were tested. Fundus examination was also performed. Patients with glaucoma, vascular retinopathies, and deep amblyopia were excluded. Mean patient age was 46years, average duration of treatment was 6years, and median dosage of cyclosporine was 200mg daily. VEP was tested in 73 patients (142 eyes) and yielded a delayed P100 wave in 9 (12.32%) (14 eyes). Among these 9 patients, abnormal findings were also noted on the Ishihara colour test in 42.86% of the eyes, and on the visual field test in 64.3% of the eyes. Abnormal VEP showed a significant correlation (p < 0.05) with older age (> 46years) and a non-significant correlation with longer duration of treatment. Higher abnormal VEP potential was not correlated with higher cyclosporine dose, and there was no correlation between abnormal VEP and blood level of cyclosporine. Optic neuropathy was significantly associated with older age in cyclosporine-treated patients. A correlation between optic neuropathy with longer duration of cyclosporine treatment was noted but was not statistically significant. We suggest that tests of optic nerve function, including VEP, be a part of the follow-up of patients receiving cyclosporine.

Incidence, microbiology, and outcomes of endophthalmitis after 111,876 pars plana vitrectomies at a single, tertiary eye care hospital.

PurposeTo describe the incidence, risk factors, clinical presentation, causative organisms, and outcomes in patients with endophthalmitis following pars plana vitrectomy (20G and minimally invasive vitrectomy surgery (MIVS).MethodsOf 111,876 vitrectomies (70,585 20-G 41,291 MIVS) performed, 45 cases developed acute-onset, postoperative endophthalmitis.ResultsThe rate of culture positive and culture negative endophthalmitis was 0.021% (2.1/10,000 surgeries) and 0.019% (1.9/10,000 surgeries) overall, 0.031% (3.1/10,000 surgeries) and 0.025% (2.5/10,000 surgeries) in 20G, and 0.005% (0.5/10,000 surgeries) and 0.007% (0.7/10,000 surgeries) in the MIVS group respectively. Potential predisposing factors were as follows: diabetes, 46.7%; vitrectomy for vascular retinopathies, 44.4%; and vitrectomy combined with anterior segment surgeries, 35.5%. The culture proven rates were 53.3% overall, 55.0% for 20G and 40.0% for MIVS. The most common organism was Pseudomonas aeruginosa for 20G. Klebsiella and Staphylococcus aureus were isolated in the two culture positive cases in MIVS group. The follow-up period for the patients with endophthalmitis was 586.14 ± 825.15 days. Seven were lost to follow up beyond one week. Of the remaining 38, 13 (34.2%) cases had a favorable visual outcome (i.e., best-corrected visual acuity [BCVA] > 5/200) and 24 (63.2%) had unfavorable visual outcome (BCVA < 5/200). Group with culture test results negative had significantly better outcomes (P < 0.05) as compared to those with positive.ConclusionsMIVS does not increase the risk of endophthalmitis. Outcomes are poor despite appropriate treatment, particularly in cases with culture results positive.

Angio-LncRs: LncRNAs that regulate angiogenesis and vascular disease.

Long noncoding RNAs (lncRNAs) represent a large subgroup of RNAs that are longer than 200 nucleotides and have no apparent protein coding potential. They have diverse functions in different biological processes by regulating chromatin remodeling or protein translation. This review summarizes the recent progress of lncRNAs in angiogenesis and vascular diseases. A general overview of lncRNA functional mechanisms will be introduced. A list of lncRNAs, which are termed “Angio-LncRs”, including MALAT1, MANTIS, PUNISHER, MEG3, MIAT, SENCR and GATA6-AS, will be discussed regarding their expression, regulation, function and mechanism of action in angiogenesis. Implications of lncRNAs in vascular diseases, such as atherosclerosis, hypertension, vascular retinopathies and tumor angiogenesis will also be discussed.

Bad vessels beware! Semaphorins will sort you out!

Secreted class 3 semaphorins (Sema3), which signal through plexin receptors and mostly use neuropilins (Nrps) as co-receptors, were initially identified for their ability to steer navigating axons in the developing embryo. They were later found to control angiogenesis in physiological and pathological settings as well (Serini et al, 2013). Indeed, the development of a novel and aberrant vasculature is central to the pathogenesis of several human diseases, including cancer and vascular retinopathies (Goel et al, 2011). A large body of evidence demonstrates that in cancer, a massive regression of angiogenesis may trigger hypoxia-driven genetic programs, which in turn can overcome drug inhibitory mechanisms and ultimately favour cancer cell invasion and dissemination. Thus, an emerging concept in molecular medicine is to devise therapeutic strategies that, rather than simply inhibiting angiogenesis, can foster the re-establishment of a structural and functional normal network, a phenomenon often referred to as “vessel normalization” (Goel et al, 2011) (Fig 1). Of note, and in this context, Sema3A (Maione et al, 2009) and Sema3F (Wong et al, 2012) have been reported to favour the normalization of cancer vasculature and impair metastatic dissemination.

Proyecto manejos integral en la DM tipo 1. Acuerdo en el manejo integral del paciente con diabetes mellit us tipo 1

IntroductionInadequate glycemic control in type 1 diabetes mellitus (DM1) is associated with the development of serious complications, so close monitoring of the disease is necessary, integrating the participation of both health professionals and the patient. ObjectiveRevalidate aspects previously identified by experts, to set the performance standard for the proper management of patients with DM1. Material and methodsThe Spanish Society of Diabetes, the Spanish Society of Endocrinology and Nutrition, and the Spanish Society of Pediatric Endocrinology promoted among their members to assess the degree of agreement and consistency with 62 selected recommendations from the literature, by a national multicenter study Delphi in 2013. ResultsA total of 164 medical specialists in DM1 of all Spanish autonomous communities, completing the entire process 150. There were no disagreements, considering consistent agreements on 5 general assertions, 9 relating to insulin therapy and 7 monitoring and management aspects of patients with DM1. ConclusionsNone disagreed with any statements expressed by previous experts, although not all have been ratified. It's considered so important basal and posprandial glycemic control, interacting inadequate glycemic control with vascular disorders, nephropathies, polyneuropathies and retinopathies. It's required insulin with a predictable and similar effect to the physiological as with insulin analogues. Diabetes education, self-control and the coordinated, multidisciplinary and personalized monitoring for each patient is essential.

Histopathologic examination of the retina following intra-vitreal propranolol administration in rabbits

Propranolol is a nonselective, beta-adrenergic receptor blocker with anti-angiogenic and anti-inflammatory effects that could be used in the treatment and control of many vascular disorder-related retinopathies. In this pilot study, the effects and complications of an intra-vitreal injection of propranolol HCl on the rabbit retina were investigated by clinical and histopathological means as the first step to determination the viability of intra-vitreal propranolol administration. Group 1 (n = 8) had 15 μg of propranolol HCL given, via intra-vitreal injection, into the right eye. Group 2 (n = 8) had a matching volume of balanced saline solution also via intra-vitreal injection into the right eye. After 4 weeks, all rabbits were killed humanely and the right eyes from both groups enucleated for histopathological study. Clinical observations and histopathological findings suggest no difference between propranolol and control groups (P ≥ 0.05). As a result of handling, in some cases, the eyes had light inflammation, hyperaemia and oedema with acute degeneration changes. This study shows that 15 μg of propranolol does not cause any significant abnormalities and is not a toxic dose for intra-vitreal injection in rabbits.