PurposeTo investigate a set of adaptive optics (AO) imaging biomarkers for the assessment of changes of the cone mosaic spatial arrangement in patients with type 1 diabetes mellitus (DM1).Methods16 patients with ≥20/20 visual acuity and a diagnosis of DM1 in the past 8 years to 37 years and 20 age-matched healthy volunteers were recruited in this study. Cone density, cone spacing and Voronoi diagrams were calculated on 160x160 μm images of the cone mosaic acquired with an AO flood illumination retinal camera at 1.5 degrees eccentricity from the fovea along all retinal meridians. From the cone spacing measures and Voronoi diagrams, the linear dispersion index (LDi) and the heterogeneity packing index (HPi) were computed respectively. Logistic regression analysis was conducted to discriminate DM1 patients without diabetic retinopathy from controls using the cone metrics as predictors.ResultsOf the 16 DM1 patients, eight had no signs of diabetic retinopathy (noDR) and eight had mild nonproliferative diabetic retinopathy (NPDR) on fundoscopy. On average, cone density, LDi and HPi values were significantly different (P<0.05) between noDR or NPDR eyes and controls, with these differences increasing with duration of diabetes. However, each cone metric alone was not sufficiently sensitive to discriminate entirely between membership of noDR cases and controls. The complementary use of all the three cone metrics in the logistic regression model gained 100% accuracy to identify noDR cases with respect to controls.ConclusionThe present set of AO imaging biomarkers identified reliably abnormalities in the spatial arrangement of the parafoveal cones in DM1 patients, even when no signs of diabetic retinopathy were seen on fundoscopy.

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BMR and plasma leptin concentrations are depressed in patients with AN; this is not explained by body-composition changes. The relation between leptin and BMR suggests that leptin plays a role in the energy sparing response to exposure to chronic energy deficiency. The return of BMR to normal and the significant increase in leptin concentrations in R-AN patients suggests a full reversibility of this adaptation mechanism.

Summary Intracavernous injection (ICI) of prostaglandin‐E1 (PGE1) is used widely as the first diagnostic test in the study of erectile dysfunction. However, a lack of full erection after a maximal dose is frequent. As well as vascular incompetence, this may be due to stress‐induced changes, related to the ICI procedure. The aim of this study was to investigate the influence of emotional disturbances on erectile response to ICI in impotent patients. Initially, 24 young men with non‐organic impotence (age 34.6 ± 1.5 years; mean ± SEM) were selected and randomized single‐blind to pharmacoerection with PGE1 alone (20 μg/mL) or a mixture (cocktail) containing 20 μg PGE1 plus an α‐adrenergic receptor blocker, phentolamine (Phe, 0.5 mg/mL). Additional studies were also performed double‐blind on 10 men with non‐organic impotence (age 37.6 ± 1.2 years) utilizing higher PGE1 dosages for ICI (25 μg/mL alone or in combination with Phe, 0.5 mg/mL). After a 7‐day interval, all subjects were crossed‐over to receive the alternative treatment. The presence of emotional disturbances was assessed in all patients by the administration of rapid tests (Stai‐X1 and Stai‐X1r for state‐anxiety before and after ICI, respectively; Stai‐X2 for trait‐anxiety; Zung‐test for depression) at the first and at the remaining (Stai‐X1 and Stai‐X1r) ICI sessions. ICI with 20 and 25 μg/mL PGE1 led to a comparable percentage of patients who reported a valid‐for‐intromission (VFI) erection (63 and 60%, respectively). In contrast, use of the cocktails significantly increased the percentage of subjects with a VFI (87 and 90% of the total number of patients tested, respectively; p <0.05). Moreover, a strong inverse correlation between state‐anxiety scores (Stai‐X1) and the erectile response to ICI with 20 and 25 μg PGE1 was found (r= ‐0.69, p<0.001); such a correlation was not present in patients who underwent ICI with the cocktails. Two cases of prolonged erection occurred (one after 20 μg PGE1 and the other after 20 μg PGE1 plus Phe) which were reversed promptly by the intracavernous injection of metharaminol. It is concluded that the lack of a full erectile response after ICI with PGE1 can be related to the presence of a high ‘state‐anxiety’ in the patients. In such patients, a VFI erectile response can be induced by the administration of a cocktail test‐dose.

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Introduction: This study aimed to evaluate the effect of treatment with eye drops containing citicoline and vitamin B 12 on changes in function of the inner retina, morphology of the inner and outer retina, and microvascular condition in patients with type 1 diabetes (DM1) with mild signs of non-proliferative diabetic retinopathy (NPDR) during 3 years of follow-up. Methods: A pilot study with prospective, randomized, and double-masked design was conducted to address the aims. Twenty patients with DM1 were enrolled and randomly divided into two groups: the DC group comprising patients treated with citicoline and vitamin B 12 eye drops (10 patients; mean age ± standard deviation, 46.86 ± 8.78 years) and the DP group comprising those treated with placebo (10 patients; mean age ± standard deviation, 47.89 ± 7.74 years). In the DC group, one eye of each patient was treated with citicoline and vitamin B 12 eye drops (OMK2 Ò , Omikron Italia srl, Italy, 3 drops/day), while in the DP group, it was treated with placebo (eye drops containing hypromellose 0.3%, 3 drops/day) for a 3-year period. In both groups, Humphrey Matrix frequency doubling technology (FDT), spectral domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA), and adaptive optics (AO) were applied at baseline and 12, 24, and 36 months of the follow-up period. Results: In the results of follow-up evaluation, the DC and DP groups were significantly different: Significant reduction in function in terms of 10-2 FDT mean sensitivity and in morphology reflected by an increase in inner nuclear layer thickness and decrease in other plexiform layer thickness and foveal vessel density were observed in the DP group, while no such significant changes were observed in the DC group in the long term. Conclusions: This pilot study indicated that patients with DM1 with mild signs of diabetic retinopathy (DR) who underwent treatment with citicoline and vitamin B 12 eye drops for a 3-year duration achieved stabilization or decreased rate of functional impairment, neuroretinal degeneration, and microvascular damage. Trial Registration: ClinicalTrials.gov identifier, NCT04009980.

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Optical coherence tomography (OCT) has recently become one of the primary methods for noninvasive probing of the human retina. The pseudoimage formed by OCT (the so-called B-scan) varies probabilistically across pixels due to complexities in the measurement technique. Hence, sensitive automatic procedures of diagnosis using OCT may exploit statistical analysis of the spatial distribution of reflectance. In this paper, we perform a statistical study of retinal OCT data. We find that the stretched exponential probability density function can model well the distribution of intensities in OCT pseudoimages. Moreover, we show a small, but significant correlation between neighbor pixels when measuring OCT intensities with pixels of about 5 µm. We then develop a simple joint probability model for the OCT data consistent with known retinal features. This model fits well the stretched exponential distribution of intensities and their spatial correlation. In normal retinas, fit parameters of this model are relatively constant along retinal layers, but varies across layers. However, in retinas with diabetic retinopathy, large spikes of parameter modulation interrupt the constancy within layers, exactly where pathologies are visible. We argue that these results give hope for improvement in statistical pathology-detection methods even when the disease is in its early stages.