Diabetic macular edema: Safe and effective treatment with intravitreal triamcinolone acetonide (Taioftal).

PURPOSE: To suggest the safety and efficacy of preservative-free triamcinolone acetonide intravitreal injectable suspension (Taioftal) for the treatment of diabetic macular edema. METHODS: A prospective clinical study involved 49 patients (49 eyes), that were treated with Taioftal and followed-up for six months. Complete ophthalmic examination, including spectral domain optical coherence tomography, was performed at baseline, and at month 1, 3, 6 after the intravitreal injection. Accurate collection and analysis of best-corrected visual acuity (BCVA), central foveal thickness (CFT), intraocular pressure (IOP), and adverse events (AEs) were carried out in order to evaluate visual function and macular morphology before and after treatment. RESULTS: Median BCVA value chosen as comparing statistics was significantly improved at every follow-up time points (gain of 6 letters at month 1, 12 at month 3 -improvement up to 24% at month 3 with stabilization until month 6) compared to baseline, as certified by Kruskal-Wallis rank sum test (P<0.05). Median CFT significantly waned at each follow-up times (decrease of about 65 µm at month 1, 155 at month 3 -reduction up to 28% at month 3 keeping good outcome until month 6) compared to baseline (P<0.05). IOP elevation, with no severe increases, was the most common among spotted AEs (median of 23 mmHg at month 1, 20 at month 3). CONCLUSION: Intravitreal injection of preservative-free triamcinolone (Taioftal) is an effective, safe and inexpensive drug used to improve visual acuity and reduce central foveal thickness in eyes affected by diabetic macular edema during an average time of 6 months. Temporary, never severe, elevation of IOP is totally manageable with topical medications. No serious vision-threatening complications are related to the use of intravitreal triamcinolone injections.

A kinematic study of skilled reaching movement in rat.

BACKGROUND: In the rat, the single-pellet reaching task includes orienting, reaching, grasping and retracting movements. It has previously been described by notation techniques, high-speed video and cineradiographic recordings. Recently, high-definition cameras have been used to track paw and digit movements with DeepLabCut, a machine-learning algorithm for markerless estimation of paw position. NEW METHOD: Our new approach consists of positioning three high-speed infrared digital cameras to track the full motion of markers on the rat's body. This provided a previously unavailable 3D recording of skilled reaching kinematics in the rat moving freely in the reaching box, which were analysed by Qualisys Track Manager software and MATLAB. RESULTS: This method enabled description of kinematic parameters unobtainable without motion tracking and provided insight into the spatiotemporal metrics of movements used to perform skilled reaching. It revealed that orientation features three steps and reaching has two bimodal start-point distributions, one along the horizontal axis and one along the vertical axis. At the end of reaching, the wrist/paw occupies the same position as the nose at the end of orienting. In grasping, averaging trajectories confirmed the marker lowering and target approaching. COMPARISON WITH EXISTING METHODS: Our method required significantly reduced time to label data and obviates the need for off-line manual marking of videos. It provides an efficient means of capturing volumes containing the entire range of marker movements. CONCLUSIONS: This study validated a new and efficient approach for quantifying rat movement kinematics, useful for comparing preclinical and clinical conditions.

Diabetic retinopathy and endothelin system: microangiopathy versus endothelial dysfunction.

In the face of the global epidemic of diabetes, it is critical that we update our knowledge about the pathogenesis of diabetes and the related micro alterations on the vascular network in the body. This may ultimately lead to early diagnosis and novel treatment options for delaying the progression of diabetic complications. Research has recently revealed the pivotal role of endothelin in the pathogenesis of diabetic complications, particularly in the regulation of the capillary flow, which is affected in the course of retinopathy. Although there are several reviews on various approaches to the treatment of diabetes, including normalization of glucose and fat metabolism, no reviews in literature have focused on the endothelin system as a therapeutic target or early indicator of diabetic microangiopathy. In this review, we summarize some of the experimental and clinical evidence suggesting that current therapeutic approaches to diabetes may include the modulation of the blood concentration of compounds of the endothelin system. In addition, we will briefly discuss the beneficial effects produced by the inhibition of the production of high levels of endothelin in vasculopathy, with focus on diabetic retinopathy. The cutting-edge technology currently widely used in opththalmology, such as the OCT angiography, allows us to detect very early retinal morphological changes alongside alterations in choroidal and retinal vascular network. Combination of such changes with highly sensitive measurements of alterations in serum concentrations of endothelin may lead to more efficient early detection and treatment of diabetes and related macro/microvascular complications.

Torsional phacoemulsification: A pilot study to revise the "harm scale" evaluating the endothelial damage and the visual acuity after cataract surgery.

PURPOSE: To study the effect of torsional phacoemulsification energy on corneal endothelium evaluating the relationship between changes of endothelial cells and postoperative visual acuity. METHODS: This prospective clinical observational cohort study included 50 patients with cataract who underwent torsional phacoemulsification. Sequential quantitative and qualitative morphometric endothelial cell analyses of the cornea were performed four weeks preoperatively and six weeks postoperatively using noncontact specular microscopy. RESULTS: This work confirmed the strong relationship, described by a linear model (one-way ANOVA, R2 = 77.9%, P < 0.0001), between the percentage of endothelial cell loss (ECL%) and the 5-score harm scale. According to the Tukey post-hoc pairwise comparison test, distinct values of ECL% are grouped in 3 subsets. The value of ECL = 10% has been identified as cut-off to discriminate patients with excellent postoperative best-corrected visual acuity (BCVA > 85 letters) from those with just a good/satisfied visual outcome (BCVA ≤ 85 letters). Within the 5-score harm scale, there was a significant correlation among phaco energy intraoperatively delivered and the average endothelial cell loss. CONCLUSIONS: This study confirms the validity of the 5-score harm scale first proposed by Sorrentino and colleagues in 2016. This time, the method categorizes cataracts taking into account nucleus hardness and phaco cumulative dissipated energy. Predicting the harm on corneal endothelium, we can discriminate patients with excellent BCVA and with just good/satisfied BCVA. With torsional phacoemulsification with respect to longitudinal, the percentage of patients who can reach excellent BCVA is remarkably increased.

The importance of glial cells in the homeostasis of the retinal microenvironment and their pivotal role in the course of diabetic retinopathy.

Diabetic retinopathy (DR) is a remarkable microvascular complication of diabetes and it has been considered the leading cause of legal blindness in working-age adults in the world. Several overlapping and interrelated molecular pathways are involved in the development of this disease. DR is staged into different levels of severity, from the nonproliferative to the advanced proliferative form. Over the years the progression of DR evolves through a series of changes involving distinct types of specialized cells: neural, vascular and glial. Prior to the clinically observable vascular complications, hyperglycemia and inflammation affect retinal glial cells which undergo a wide range of structural and functional alterations. In this review, we provide an overview of the status of macroglia and microglia in the course of DR, trying to briefly take into account the complex biochemical mechanisms that affect the intimate relationship among neuroretina, vessels and glial cells.

A Pilot Study to Propose a "Harm Scale", a New Method to Predict Risk of Harm to the Corneal Endothelium Caused by Longitudinal Phacoemulsification, and the Subsequent Effect of Endothelial Damage on Post Operative Visual Acuity.

PURPOSE: To study the effect of longitudinal phacoemulsification energy on corneal endothelium and to evaluate the relationship between changes of endothelial cells and postoperative visual acuity. METHODS: This prospective clinical observational cohort study included 50 patients with cataract who underwent longitudinal phacoemulsification. Sequential quantitative and qualitative morphometric endothelial cell analyses of the cornea were performed 4 weeks preoperatively and 6 weeks postoperatively using noncontact specular microscopy. RESULTS: There was a relationship between ECL percentage (ECL%) and the 5-score harm scale, well-described by a linear model (one-way ANOVA, R2 = 73.3%). Analyzing the distribution of ECL% Mean with Tukey post-hoc pairwise comparison test (P < 0.001), the value of ECL = 20% has been regarded as cut-off to discriminate patients who obtained an excellent postoperative best-corrected visual acuity (BCVA > 85 letters) from those who just had a good visual outcome (BCVA ≤ 85 letters). There was a significant correlation among the 5-score harm scale, phaco energy intraoperatively delivered, and average cell area postoperatively. CONCLUSIONS: The 5-score harm scale, a new method that enables to pigeonhole cataracts taking into account nucleus hardness and phaco times, allows to predict the harm on corneal endothelium after longitudinal phacoemulsification. Assessment of ECL% permits to discriminate between patients with excellent BCVA and with just good BCVA, postoperatively.

The Role of the Endothelin System in the Vascular Dysregulation Involved in Retinitis Pigmentosa.

Retinitis pigmentosa is a clinical and genetic group of inherited retinal disorders characterized by alterations of photoreceptors and retinal pigment epithelium leading to a progressive concentric visual field restriction, which may bring about severe central vision impairment. Haemodynamic studies in patients with retinitis pigmentosa have demonstrated ocular blood flow abnormalities both in retina-choroidal and in retroocular vascular system. Moreover, several investigations have studied the augmentation of endothelin-1 plasma levels systemically in the body and locally in the eye. This might account for vasoconstriction and ischemia, typical in vascular dysregulation syndrome, which can be considered an important factor of reduction of the ocular blood flow in subjects affected by retinitis pigmentosa.

Complex movement topography and extrinsic space representation in the rat forelimb motor cortex as defined by long-duration intracortical microstimulation.

Electrical stimulation of the motor cortex in the rat can evoke complex forelimb multi-joint movements, including movement of limb and paw. In this study, these movements have been quantified in terms of 3D displacement and kinematic variables of two markers positioned on the wrist and middle digits (limb and paw movement, respectively). Electrical microstimulation was applied to the motor cortex using a pulse train of 500 ms duration. Movements were measured using a high-resolution 3D optical system. Five classes of limb movements (abduction, adduction, extension, retraction, elevation) and four classes of paw movements (opening, closure, opening/closure sequence, supination) were described according to their kinematics. A consistent topography of these classes of movements was presented across the motor cortex together with a topography of spatial locations to which the paw was directed. In about one-half of cortical sites, a specific pattern of limb-paw movement combination did exist. Four categories of limb-paw movements resembling behavioral repertoire were identified: reach-shaping, reach-grasp sequence, bring-to-body, and hold-like movement. Overall, the forelimb motor region included: (1) a large caudal forelimb area dominated by reach-shaping movement representation; (2) a small rostral area containing reach-grasp sequence and bring-to-body movement representation; and (3) a more lateral portion where hold-like movement was represented. These results support the view that, in rats, the motor cortex controls forelimb movements at a relatively complex level and suggest that the orderly representation of complex movements and their dynamics/kinematics emerge from the principles of forelimb motor cortex organization.

Automatic online spike sorting with singular value decomposition and fuzzy C-mean clustering.

BACKGROUND: Understanding how neurons contribute to perception, motor functions and cognition requires the reliable detection of spiking activity of individual neurons during a number of different experimental conditions. An important problem in computational neuroscience is thus to develop algorithms to automatically detect and sort the spiking activity of individual neurons from extracellular recordings. While many algorithms for spike sorting exist, the problem of accurate and fast online sorting still remains a challenging issue. RESULTS: Here we present a novel software tool, called FSPS (Fuzzy SPike Sorting), which is designed to optimize: (i) fast and accurate detection, (ii) offline sorting and (iii) online classification of neuronal spikes with very limited or null human intervention. The method is based on a combination of Singular Value Decomposition for fast and highly accurate pre-processing of spike shapes, unsupervised Fuzzy C-mean, high-resolution alignment of extracted spike waveforms, optimal selection of the number of features to retain, automatic identification the number of clusters, and quantitative quality assessment of resulting clusters independent on their size. After being trained on a short testing data stream, the method can reliably perform supervised online classification and monitoring of single neuron activity. The generalized procedure has been implemented in our FSPS spike sorting software (available free for non-commercial academic applications at the address: http://www.spikesorting.com) using LabVIEW (National Instruments, USA). We evaluated the performance of our algorithm both on benchmark simulated datasets with different levels of background noise and on real extracellular recordings from premotor cortex of Macaque monkeys. The results of these tests showed an excellent accuracy in discriminating low-amplitude and overlapping spikes under strong background noise. The performance of our method is competitive with respect to other robust spike sorting algorithms. CONCLUSIONS: This new software provides neuroscience laboratories with a new tool for fast and robust online classification of single neuron activity. This feature could become crucial in situations when online spike detection from multiple electrodes is paramount, such as in human clinical recordings or in brain-computer interfaces.

Principal component analysis of scintimammographic images.

The recent development of new gamma imagers based on scintillation array with high spatial resolution, has strongly improved the possibility of detecting sub-centimeter cancer in Scintimammography. However, Compton scattering contamination remains the main drawback since it limits the sensitivity of tumor detection. Principal component image analysis (PCA), recently introduced in scintimam nographic imaging, is a data reduction technique able to represent the radiation emitted from chest, breast healthy and damaged tissues as separated images. From these images a Scintimammography can be obtained where the Compton contamination is "removed". In the present paper we compared the PCA reconstructed images with the conventional scintimammographic images resulting from the photopeak (Ph) energy window. Data coming from a clinical trial were used. For both kinds of images the tumor presence was quantified by evaluating the t-student statistics for independent sample as a measure of the signal-to-noise ratio (SNR). Since the absence of Compton scattering, the PCA reconstructed images shows a better noise suppression and allows a more reliable diagnostics in comparison with the images obtained by the photopeak energy window, reducing the trend in producing false positive.