Two-year visual field outcomes of the treatment for advanced glaucoma study (TAGS)

PURPOSE: to compare visual field (VF) progression between the two arms of the Treatment of Advanced Glaucoma Study (TAGS) DESIGN: post-hoc analysis of VF data from a two-arm multicenter randomized controlled clinical trial METHODS: 453 patients with newly diagnosed advanced open-angle glaucoma in at least one eye from 27 centers in the United Kingdom were randomized to either trabeculectomy (N = 227) or medications in their index eye (N = 226) and followed-up for two years with two 24-2 VF tests at baseline, 4, 12 and 24 months. We analyzed data for participants with a reliable VF (False positive rate < 15%) at baseline and at least two other time-points. MAIN OUTCOME MEASURES: Average difference in rate of progression (RoP) was analyzed using a hierarchical Bayesian model. Time for each eye to progress from baseline beyond specific cut-offs (0.5, 1, 1.5 and 2 dB) was compared using survival analysis. RESULTS: 211 eyes in the trabeculectomy-first arm and 203 eyes in the medications-first arm were analyzed. The average RoPs (Estimate [95% Credible Intervals]) were -0.59 [-0.88, -0.31] dB/year in the medications-first arm and -0.40 [-0.67, -0.13] dB/year in the trabeculectomy-first arm. The difference was not significant (Bayesian p-value = 0.353). More eyes progressed in the medications-first arm: ≥0.5 dB (p = 0.001), ≥1dB (p = 0.014), ≥1.5dB (p = 0.071) and ≥2dB (p = 0.061). CONCLUSIONS: there was no significant difference in the average RoP at two years. Initial trabeculectomy significantly reduced the proportion of progressing eyes

Spatiotemporal summation of perimetric stimuli in healthy observers

Spatial summation of perimetric stimuli has been used to derive conclusions about the spatial extent of retinal-cortical convergence, mostly from the size of the critical area of summation (Ricco's area, RA) and critical number of retinal ganglion cells (RGCs). However, spatial summation is known to change dynamically with stimulus duration. Conversely, temporal summation and critical duration also vary with stimulus size. Such an important and often neglected spatiotemporal interaction has important implications for modeling perimetric sensitivity in healthy observers and for formulating hypotheses for changes measured in disease. In this work, we performed experiments on visually heathy observers confirming the interaction of stimulus size and duration in determining summation responses in photopic conditions. We then propose a simplified computational model that captures these aspects of perimetric sensitivity by modelling the total retinal input, the combined effect of stimulus size, duration, and retinal cones-to-RGC ratio. We additionally show that, in the macula, the enlargement of RA with eccentricity might not correspond to a constant critical number of RGCs, as often reported, but to a constant critical total retinal input. We finally compare our results with previous literature and show possible implications for modeling disease, especially glaucoma

A fluid-dynamic based approach to reconnect the retinal vessels in fundus photography

This paper introduces the use of fluid-dynamic modeling to determine the connectivity of overlapping venous and arterial vessels in fundus images. Analysis of the retinal vascular network may provide information related to systemic and local disorders. However, the automated identification of the vascular trees in retinal images is a challenging task due to the low signal-to-noise ratio, nonuniform illumination and the fact that fundus photography is a projection on to the imaging plane of three-dimensional retinal tissue. A zero-dimensional model was created to estimate the hemodynamic status of candidate tree configurations. Simulated annealing was used to search for an optimal configuration. Experimental results indicate that simulated annealing was very efficient on test cases that range from small to medium size networks, while ineffective on large networks. Although for large networks the nonconvexity of the cost function and the large solution space made searching for the optimal solution difficult, the accuracy (average success rate = 98.35%), and simplicity of our novel approach demonstrate its potential effectiveness in segmenting retinal vascular trees

Spatial summation in the glaucomatous macula: a link with retinal ganglion cell damage

Purpose: to test whether functional loss in the glaucomatous macula is characterised by an enlargement of Ricco’s area (RA) through the application of a computational model linking retinal ganglion cell (RGC) damage to perimetric sensitivity Methods: one eye from each of 29 visually-healthy subjects <40 years old, 30 glaucoma patients and 20 age-similar controls was tested with a 10-2 grid with stimuli of five different area sizes. Structural estimates of point-wise RGC density were obtained from Optical Coherence Tomography scans. Structural and functional data from the young healthy cohort were used to estimate the parameters of a computational spatial summation model to generate a template. The template was fitted with a Bayesian hierarchical model to estimate the latent RGC density in glaucoma patients and agematched controls. We tested two alternative hypotheses: fitting the data by translating the template horizontally (H1: change in RA) or vertically (H2: loss of sensitivity without change in RA). Root Mean Squared Error (RMSE) of the model fits to perimetric sensitivity were compared. 95%-Confidence Intervals were bootstrapped. The dynamic range of the functional and structural RGC density estimates was denoted by their 1st and the 99th percentile. Results: the RMSE was 2.09 [1.92-2.26] under H1 and 2.49 [2.24-2.72] under H2 (p < 0.001). The average dynamic range for the structural RGC density estimates was only 11% that of the functional estimates. Conclusions: macular sensitivity loss in glaucoma is better described by a model in which RA changes with RGC loss. Structural measurements have limited dynamic range

Spatial distribution of early red lesions is a risk factor for development of vision-threatening diabetic retinopathy

Aims/hypothesis Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study was to map accurately the area where lesions could predict progression to vision-threatening retinopathy. Methods The predictive value of the location of the earliest red lesions representing haemorrhages and/or microaneurysms was studied by comparing their occurrence in a group of individuals later developing vision-threatening diabetic retinopathy with that in a group matched with respect to diabetes type, age, sex and age of onset of diabetes mellitus who did not develop vision-threatening diabetic retinopathy during a similar observation period. Results The probability of progression to vision-threatening diabetic retinopathy was higher in a circular area temporal to the fovea, and the occurrence of the first lesions in this area was predictive of the development of vision-threatening diabetic retinopathy. The calculated peak value showed that the risk of progression was 39.5% higher than the average. There was no significant difference in the early distribution of lesions in participants later developing diabetic maculopathy or proliferative diabetic retinopathy. Conclusions/interpretation The location of early red lesions in diabetic retinopathy is predictive of whether or not individuals will later develop vision-threatening diabetic retinopathy. This evidence should be incorporated into risk models used to recommend control intervals in screening programmes for diabetic retinopathy

Effectiveness of cardiac resynchronization therapy in heart failure patients with valvular heart disease: comparison with patients affected by ischaemic heart disease or dilated cardiomyopathy. The InSync/InSync ICD Italian Registry

AimsTo analyse the effectiveness of cardiac resynchronization therapy (CRT) in patients with valvular heart disease (a subset not specifically investigated in randomized controlled trials) in comparison with ischaemic heart disease or dilated cardiomyopathy patients.Methods and resultsPatients enrolled in a national registry were evaluated during a median follow-up of 16 months after CRT implant. Patients with valvular heart disease treated with CRT (n = 108) in comparison with ischaemic heart disease (n = 737) and dilated cardiomyopathy (n = 635) patients presented: (i) a higher prevalence of chronic atrial fibrillation, with atrioventricular node ablation performed in around half of the cases; (ii) a similar clinical and echocardiographic profile at baseline; (iii) a similar improvement of LVEF and a similar reduction in ventricular volumes at 6-12 months; (iv) a favourable clinical response at 12 months with an improvement of the clinical composite score similar to that occurring in patients with dilated cardiomyopathy and more pronounced than that observed in patients with ischaemic heart disease; (v) a long-term outcome, in term of freedom from death or heart transplantation, similar to patients affected by ischaemic heart disease and basically more severe than that of patients affected by dilated cardiomyopathy.ConclusionIn 'real world' clinical practice, CRT appears to be effective also in patients with valvular heart disease. However, in this group of patients the outcome after CRT does not precisely overlap any of the two other groups of patients, for which much more data are currently available

Global tortuosity estimation of retinal vessel network in wide-field images taken from infants with retinopathy of prematurity

Determinare ed implementare un criterio automatico di tortuosità consistente con il giudizio dei clinici per ottenere una misura che possa fornire un ordinamento coerente con quelli degli espert