Cerebral haemodynamics in cirrhotic patients with hepatic encephalopathy.

BACKGROUND & AIMS: Factors other than elevated levels of ammonia may be implicated in hepatic encephalopathy (HE) pathophysiology, including abnormal cerebral haemodynamics. Transcranial Doppler ultrasonography (TCD) evaluates cerebrovascular structural integrity and reactivity, through pulsatility index (PI) and breath-holding index (BHI) respectively. The aim of this study was to evaluate cerebral haemodynamics by TCD in patients with compensated and decompensated cirrhosis, and patients with and without HE. METHODS: We studied 90 subjects by TCD measuring PI and BHI in the middle cerebral artery: 30 with cirrhosis and no HE, 30 with cirrhosis and low-grade HE and 30 healthy subjects. Critical flicker frequency, psychometric hepatic encephalopathy score and West-Haven criteria were performed to assess MHE and HE respectively. RESULTS: Pulsatility index increased in decompensated cirrhotics (Child ≥ 7) when compared with compensated cirrhotics and healthy subjects [median (IQR) 1.07 (0.95-1.21) vs 0.90 (0.83-1.05) vs 0.87 (0.78-0.96); P < 0.001]. A reverse relationship was observed for BHI among the three groups [0.82 (0.45-1.11) vs 1.20 (0.82-1.52) vs 1.28 (1.06-1.68); P < 0.001]. Similar findings were observed in decompensation [model for end-stage liver disease (MELD) score ≥14]. Patients with HE showed higher PI and lower BHI [1.05 (1.00-1.16) and 0.89 (0.59-1.15)], when compared with patients without HE [0.96 (0.83-1.13) and 1.00 (0.60-1.53)] or controls [0.87 (0.78-0.96) and 1.28 (1.06-1.68)] (P < 0.001 for PI, and P = 0.007 for BHI). In multivariate regression models, only PI predicted HE, but it was outperformed by MELD-sodium and tumour necrosis factor-alpha. CONCLUSIONS: These results indicate that cerebral haemodynamics are altered in patients with cirrhosis, in relation to severity of disease and HE. Findings on impaired PI and BHI suggest that structural vascular damage and loss of vascular autoregulation are implicated in the pathophysiology of HE.

In Vivo Correlation Between Macular Pigment Optical Volume and Retinal Layers Thickness.

Purpose: This study aims to investigate the potential in vivo relationship between macular pigment (MP) and retinal layers thickness in healthy subjects and dry, non-advanced age-related macular degeneration (AMD). Methods: An observational, cross-sectional study was conducted. Healthy subjects >40 years and patients with early or intermediate AMD were recruited. Structural OCT and macular pigment optical volume (MPOV) were collected for each subject. Retinal layers parameters were calculated based on the standard early treatment diabetic retinopathy study (ETDRS) map. Additionally, MPOV within 1°, 2°, and 9° of eccentricity was assessed and associated with retinal layers thickness and volume. Linear mixed-effects models were used to test the relationship between MP and structural OCT parameters, while adjusting for known possible confounding factors. Results: A total of 144 eyes of 91 subjects (60.4% females) were evaluated, comprising 43% normal eyes and 57% with early/intermediate AMD. Among the retinal layers, only the outer nuclear layer (ONL) thickness and volume appeared to be associated to higher MP levels. Specifically, the central ONL thickness was identified as a significant predictor of the MPOV 1°(P = 0.04), while the parafoveal ONL thickness (inner ETDRS subfield) was identified as a significant fixed effect on the MPOV 9° (P = 0.037). Age and the presence of drusen or subretinal drusenoid deposits were also tested without showing significant correlations. Conclusions: Among the retinal layers examined, only the ONL thickness demonstrated a significant association with MPOV. Consequently, ONL thickness might serve as a potential biomarker related to MP levels.

Comment on Richer et al. Night Vision and Carotenoids (NVC): A Randomized Placebo Controlled Clinical Trial on Effects of Carotenoid Supplementation on Night Vision in Older Adults. Nutrients 2021, 13, 3191.

Richer and colleagues [...].

Impact of symptomatic vitreous degeneration on photopic and mesopic contrast thresholds.

CLINICAL RELEVANCE: Contrast thresholds under photopic and mesopic luminance conditions are compromised in subjects with vitreous degeneration. A plausible explanation is needed for the visual discomfort expressed by patients suffering from symptomatic vitreous degeneration. BACKGROUND: The current study investigates the effect of symptomatic vitreous degeneration on photopic and mesopic contrast at high spatial frequencies. METHODS: An age-matched sample of 115 subjects, comprising 30 subjects with symptomatic vitreous floaters (cases) and 85 healthy subjects (controls), was included in this study. Visual acuity and flicker thresholds were measured for all participants. Photopic and mesopic functional contrast thresholds at 10 cycles per degree were measured for all participants to assess the effect of floaters on contrast. Further, to determine the effect of posterior vitreous detachment on contrast, the sample was divided into three groups: cases with posterior vitreous detachment (n = 12); cases without posterior vitreous detachment (n = 18); and controls (n = 85), and their contrast thresholds were compared. RESULTS: Photopic and mesopic contrast thresholds were lower by 37.4% and 27.5%, respectively, when the cases were compared with the controls (p = 0.028 and p < 0.001 for photopic and mesopic contrast thresholds, respectively). Photopic contrast was lower by 64.0% in cases with posterior vitreous detachment compared with controls (p = 0.001). Compared with controls, mesopic contrast was lower in cases with posterior vitreous detachment and in cases without posterior vitreous detachment by 30.3% and 25.6%, respectively (p = 0.014 and p = 0.017 for cases with and without posterior vitreous detachment, respectively). CONCLUSION: : Subjects with vitreous degeneration have diminished photopic and mesopic contrast thresholds compared with controls. This finding highlights the negative impact of vitreous degeneration on the quality of vision.

Environmental and Nutritional Determinants of Macular Pigment in a Mexican Population.

Purpose: The carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin deposit at the macula as macular pigment (MP) and provide visual benefits and protection against macular diseases. The present study investigated MP, its nutritional and environmental determinants, and its constituent carotenoids in serum from a Mexican sample, in healthy participants and with metabolic diseases. Additionally, we compared these variables with an Irish sample. Methods: MP was measured in 215 subjects from a rural community in Mexico with dual-wavelength autofluorescence imaging reported as MP optical volume (MPOV). Dietary intake and serum concentrations of L and Z were evaluated. Results: The mean MPOV was 8429 (95% confidence interval, 8060-8797); range. 1171-15,976. The mean L and Z serum concentrations were 0.25 ± 0.15 µmol/L and 0.09 ± 0.04 µmol/L, respectively. The MPOV was positively correlated with L and Z serum concentrations (r = 0.347; P < 0.001 and r = 0.311; P < 0.001, respectively), but not with L + Z dietary estimates. Subjects with daily sunlight exposure of more than 50% were found to have significantly higher MPOV than those with less than 50% (P = 0.005). MPOV and serum concentrations of L and Z were significantly higher in the Mexican sample compared with the Irish sample, but this difference was not reflected in dietary analysis. Conclusions: These new data from a Mexican sample provide evidence of the multifactorial interactions and environmental determinants of MP such as sunlight exposure and dietary patterns. These findings will be essential for future studies in Mexico for eye health, visual function, and ocular pathology.

Dietary Intervention With a Targeted Micronutrient Formulation Reduces the Visual Discomfort Associated With Vitreous Degeneration.

Purpose: To investigate the impact of supplementation with a targeted micronutrient formulation on the visual discomfort associated with vitreous degeneration. Methods: In this clinical trial, 61 patients with symptomatic vitreous floaters were randomized to consume daily, the active supplement consisting of 125 mg L-lysine, 40 mg vitamin C, 26.3 mg Vitis vinifera extract, 5 mg zinc, and 100 mg Citrus aurantium or placebo for 6 months. Change in visual discomfort from floaters, assessed with the Floater Disturbance Questionnaire, was the primary outcome measure. Secondary outcome measures included best-corrected visual acuity, letter contrast sensitivity, photopic functional contrast sensitivity with positive and negative contrast polarity, and quantitative vitreous opacity areas. Results: After supplementation, the active group reported a significant decrease in their visual discomfort from floaters (P < 0.001), whereas the placebo group had no significant change in their visual discomfort (P = 0.416). At 6 months, there was a significant decrease in vitreous opacity areas in the active group (P < 0.001) and an insignificant increase in vitreous opacity areas in the placebo group (P = 0.081). Also, there was a significant improvement in photopic functional contrast sensitivity with positive contrast polarity in the active group after supplementation (P = 0.047). Conclusions: The findings of this study indicate improvements in vision-related quality of life and visual function of patients suffering from vitreous floaters after supplementation with a formulation of antioxidative and antiglycation micronutrients. Notably, these improvements were confirmed by the decrease in vitreous opacity areas in the active group. Translational Relevance: This targeted dietary intervention should be considered to support patients with symptomatic vitreous degeneration.

The Impact of Formulation on Lutein, Zeaxanthin, and meso-Zeaxanthin Bioavailability: A Randomised Double-Blind Placebo-Controlled Study.

Lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) have been the focus of research and commercial interest for their applications in human health. Research into formulations to enhance their bioavailability is merited. This 6 month randomised placebo-controlled trial involving 81 healthy volunteers compared the bioavailability of different formulations of free L, Z, and MZ in sunflower or omega-3 oil versus L, Z, and MZ diacetates (Ld, Zd, and MZd) in a micromicellar formulation. Fasting serum carotenoids, macular pigment, and skin carotenoid score were analysed at baseline and 6 months. Serum L, Z, and MZ concentrations increased in all active interventions compared to placebo (p < 0.001 to p = 0.008). The diacetate micromicelle formulation exhibited a significantly higher mean response in serum concentrations of Z and MZ compared to the other active interventions (p = 0.002 to 0.019). A micromicellar formulation with solubilised Z and MZ diacetates is a promising technology advancement that enhances the bioavailability of these carotenoids when compared to traditional carotenoid formulations (ISRCTN clinical trial registration number: ISRCTN18206561).

Standardizing the Assessment of Macular Pigment Using a Dual-Wavelength Autofluorescence Technique.

PURPOSE: It is essential to have an appropriate measure to assess macular pigment (MP) that can provide an accurate, valid, and reliable representation of the MP within the macula. The aim of this study was to describe and introduce MP optical volume (MPOV) as an optimal value for reporting MP. METHODS: Three hundred ninety-three subjects were analyzed using the Heidelberg Spectralis with the investigational MP optical density (MPOD) module to measure MPOV and MPOD at four foveal eccentricities (0.23°, 0.51°, 0.98°, 1.76° [7° as reference point]). Lutein (L) and zeaxanthin (Z) dietary intake and serum concentrations were evaluated. RESULTS: MPOV mean was 5094 (95%CI, 4877-5310); range: 527 to 10,652. MPOV was inversely correlated with body mass index and positively correlated with education (r = -0.156, P = 0.002 and r = 0.124, P = 0.014, respectively). Serum concentrations of L and Z were positively correlated with MPOV (r = 0.422, P < 0.001 and r = 0.285, P < 0.001, respectively). MPOV was positively correlated to MPOD at all measured eccentricities, with the strongest agreement at 1.76° (r = 0.906, P < 0.001). Serum concentrations of L and Z, BMI, education, and age (P < 0.001) were found to be significant predictors of MPOV. CONCLUSIONS: The Spectralis MPOV measurement provided a comprehensive and detailed evaluation of the MP profile. The Spectralis MPOV should be considered a preferred metric for the assessment of MP. TRANSLATIONAL RELEVANCE: Applying a standardized method for the assessment and report of MP will allow to fully derive meaning from observational studies and to successfully implement this MP measurement technique in research and clinical settings.