Role of nitric oxide in optic nerve head blood flow regulation during an experimental increase in intraocular pressure in healthy humans.

The present study set out to investigate whether nitric oxide, a potent vasodilator, is involved in the regulatory processes in optic nerve head blood flow during an experimental increase in intraocular pressure (IOP). The study was conducted in a randomized, double-masked, placebo-controlled, three way cross-over design. 12 healthy subjects were scheduled to receive either L-NMMA (an unspecific nitric oxide synthase inhibitor), phenylephrine (an α-adrenoceptor agonist) or placebo on three different study days. Optic nerve head blood flow was measured using laser Doppler flowmetry and IOP was increased stepwise with a suction cup. Mean arterial pressure (MAP) and IOP were measured non-invasively and ocular perfusion pressure (OPP) was calculated as OPP = 2/3 MAP-IOP. Administration of L-NMMA and phenylephrine significantly increased MAP and therefore OPP at rest (p < 0.01). L-NMMA significantly reduced baseline blood flow in the optic nerve head (p < 0.01). Application of the suction cup induced a significant increase in IOP and a decrease in OPP (p < 0.01). During the stepwise increase in IOP, some autoregulatory potential was observed until OPP decreased approximately -30% below baseline. None of the administered substances had an effect on this autoregulatory behavior (p = 0.49). The results of the present study confirm that the human optic nerve head shows some regulatory capacity during a decrease in OPP. Nitric oxide is involved in the regulation of basal vascular tone in the optic nerve head but does not seem to be involved in the regulatory mechanisms during an acute increase in IOP in young healthy subjects.

Short- and mid-term repeatability of macular pigment optical density measurements using spectral fundus reflectance.

BACKGROUND: Several methods have been proposed for measuring macular pigment optical density (MPOD). To date, none of the realized techniques can be considered as "gold standard". A key issue for the clinical applicability of a method is its repeatability. In this study, we investigated short- and mid-term repeatability of MPOD measurements using reflectometry. METHODS: A total of 12 healthy young subjects were measured 5 times on 5 consecutive days. Repeatability over 6 months was investigated in patients with AMD. The data in AMD patients were taken from a recently published placebo controlled study investigating the effect of lutein supplementation on MPOD (n = 37; [1]). Four measurements over 6 months were used to calculate repeatability. Spectral fundus reflectance of the fovea was measured in a 2.3° detection field with a custom-built fundus reflectometer. Calculation of MPOD was based on a previously published fundus reflectance model. RESULTS: The coefficients of variation were 6.2 ± 2.4% and 8.0 ± 5.5% in the healthy and AMD group, respectively. Bland-Altman plots indicate that the difference between measurements at day 1 and day 5 in healthy subjects and day 1 and month 6 in AMD patients was small. The maximum deviation in MPOD in a healthy subject was 0.07 (22.6%), and 0.17 (51.5%) in a patient with AMD. CONCLUSIONS: Reflectometry provides adequate short-term and mid-term repeatability for measuring MPOD. Accordingly, the technique makes it possible to monitor MPOD in patients with AMD and to study the influence of supplementation in these subjects. In addition, the variability of the technique is small enough to allow for clinical trials with reasonable sample size.

Changes in Retinal Blood Flow in Response to an Experimental Increase in IOP in Healthy Participants as Assessed With Doppler Optical Coherence Tomography.

Purpose: Blood flow autoregulation is an intrinsic mechanism of the healthy retinal vasculature to keep blood flow constant when ocular perfusion pressure (OPP) is changed. In the present study, we set out to investigate retinal blood flow in response to an experimental decrease in OPP in healthy participants using Doppler optical coherence tomography. Methods: Fifteen healthy participants aged between 22 and 31 years (mean, 27 ± 3 years) were included in the present open study. IOP was increased stepwise via the suction cup method to induce a decrease in OPP. Retinal blood flow in arteries and veins was assessed using a custom-built Doppler optical coherence tomography system and pressure-flow relationships were calculated to assess autoregulation. Results: Suction cup application induced a pronounced increase in IOP with a maximum value of 50.5 ± 8.0 mm Hg at the highest level of suction. Pressure-flow relationships revealed that blood flow was autoregulated until the OPP was decreased by approximately 21 mm Hg and started to decrease significantly when the OPP was reduced by 30 mm Hg. Retinal blood flow at the last suction period decreased at a maximum of -57.0 ± 22.3% and 65.2 ± 15.4% in retinal arteries and retinal veins, respectively. These changes in retinal blood flow were less pronounced than the decrease in OPP (-75.2 ± 19.2%), indicating retinal autoregulation. Conclusions: The results of the present study confirm that retinal blood flow is autoregulated in response to changes in the OPP. Doppler optical coherence tomography has the potential to become a clinical tool for the investigation of retinal blood flow autoregulation in the future, because of its ability to assess the blood velocities and diameter of the retinal vessels parallel and therefore also their blood flow in absolute values. (Clinicaltrials.gov number NCT03398616).

Automatic assessment of tear film and tear meniscus parameters in healthy subjects using ultrahigh-resolution optical coherence tomography.

Many different parameters exist for the investigation of tear film dynamics. We present a new tear meniscus segmentation algorithm which automatically extracts tear meniscus area (TMA), height (TMH), depth (TMD) and radius (TMR) from UHR-OCT measurements and apply it to a data set including repeated measurements from ten healthy subjects. Mean values and standard deviations are 0.0174 ± 0.007 mm2, 0.272 ± 0.069 mm, 0.191 ± 0.049 mm and 0.309 ± 0.123 mm for TMA, TMH, TMD and TMR, respectively. A significant correlation was found between all respective tear meniscus parameter pairs (all p < 0.001, all Pearson's r ≥ 0.657). Challenges, limitations and potential improvements related to the data acquisition and the algorithm itself are discussed. The automatic segmentation of tear meniscus measurements acquired with UHR-OCT might help in a clinical setting to further understand the tear film and related medical conditions like dry eye disease.

Estimating Retinal Blood Flow Velocities by Optical Coherence Tomography.

IMPORTANCE: While optical coherence tomography (OCT) angiography has been considered to evaluate retinal capillary blood flow instead of fluorescein angiography, the reflectance pattern of blood vessels on structural OCT might also provide retinal capillary flow data in the absence of fluorescein angiography. This potential has been insufficiently explored, despite promising data concerning a possible relationship between the reflectance pattern of blood vessels and their perfusion velocity in a laboratory setting. OBJECTIVE: To evaluate the potential of retinal blood flow velocity estimation by structural OCT. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional observational study conducted from June to November 2015 at a tertiary clinical referral center. Sixty arteries (the superior and inferior temporal arteries) from 30 eyes of 30 patients (17 female, 13 male) were included in the study. MAIN OUTCOMES AND MEASURES: Based on the intraluminal contrast patterns of retinal arteries on OCT, 3 independent graders categorized the blood flow velocities as low, medium, or high. These results and the results from a software-based intraluminal contrast analysis were compared with the retinal blood flow velocities measured by video fluorescein angiography. RESULTS: Among the 30 eyes of 30 patients (mean [SD] age, 72.6 [12.3] years; 17 female, 13 male), 15 were controls without retinal occlusion, 6 had a branch retinal artery occlusion, and 9 had a central retinal artery occlusion. When discriminating between low flow velocities and medium or high flow velocities, the graders' sensitivity ranged from 88.2% to 100% (grader 1: 88.2%; 95% CI, 63.6%-98.5%; grader 2: 88.2%; 95% CI, 63.6%-98.5%; and grader 3: 100%; 95% CI, 69.8%-100%) and their specificity ranged from 97.6% to 100% (grader 1: 100%; 95% CI, 87.7%-100%; grader 2: 97.6%; 95% CI, 87.4%-99.9%; and grader 3: 100%; 95% CI, 87.7%-100%). The κ coefficients of the comparison between the 3 graders and the angiography were 0.77 (95% CI, 0.60-0.93; P < .001), 0.64 (95% CI, 0.44-0.83; P < .001), and 0.87 (95% CI, 0.74-0.99; P < .001). In the computer-based assessment, the contrast reduction of the intraluminal pattern could be numerically expressed in a specific coefficient in the model (I2, describing the angular change of the backscattering intensity in the model), which presented nonoverlapping intervals between low flow velocities and medium or high flow velocities (mean [SD] I2, 0.3 [5.3], 20.4 [6.4], and 21.7 [4.0], respectively). CONCLUSIONS AND RELEVANCE: This study suggests that a low retinal blood flow velocity reflects in a visually distinct contrast reduction of the intraluminal pattern of retinal vessels on OCT. Larger studies are required to assess the clinical benefits.

The association between subjective and objective parameters for the assessment of dry-eye syndrome.

PURPOSE: The aim of the present study was to evaluate the association between symptoms and different clinical signs in patients with dry-eye syndrome (DES). METHODS: Fifty-two patients with DES were included in the present cross-sectional study. For assessment of symptoms, the Ocular Surface Disease Index (OSDI) was used. Clinical parameters included measurement of tear break up time (BUT), corneal fluorescein staining, tear osmolarity, and ocular scattering index (OSI). Tear film thickness (TFT) was assessed using a custom-built optical coherence tomography (OCT) system with an axial resolution of 1.2 µm. In addition, impression cytology was performed. Correlation coefficients were calculated using linear regression analysis. RESULTS: The mean OSDI in the present study population was 28.9 ± 17.6, the mean TFT was 4.1 ± 1.3 µm. A significant negative correlation was found between OSDI and TFT (r = -0.34, P = 0.01). Tear film thickness correlated positively with BUT (r = 0.35, P = 0.01), but with no other signs of DES. No association was found between OSDI and the other evaluated signs. CONCLUSIONS: The study population mainly comprised of patients with mild to moderate DES. Tear film thickness as measured with a custom-built OCT device correlated with subjective symptoms in these patients. In agreement with previous data, the association between other signs and symptoms was weak in the present study. Measurement of TFT with OCT may become a valuable tool in the management of DES patients. (ClinicalTrials.gov number, NCT01753687.)

Comparison of macular pigment in patients with age-related macular degeneration and healthy control subjects - a study using spectral fundus reflectance.

PURPOSE: Previous studies have reported an age-dependent decline of macular pigment optical density (MPOD) as well as a relative lack of MPOD in age-related macular degeneration (AMD). Results are, however, strongly dependent on the technique used. In this study, we investigated the age dependence of MPOD using spectral fundus reflectance. In addition, we hypothesized that patients with AMD have a reduced MPOD as compared to healthy controls. METHODS: A total of 85 healthy subjects and 96 patients with AMD were included in this study. The healthy control subjects showed a wide range of ages (mean, 51.6 years; range, 21-79years). Patients with AMD were significantly older (mean, 71.2 years; range, 50-89 years). Spectral fundus reflectance of the fovea was measured in a 2.3° detection field with a custom built fundus reflectometer. Calculation of MPOD was based on a previously published fundus reflectance model. RESULTS: Patients with AMD showed a reduced MPOD (0.35 ± 0.12) as compared to the healthy control group (0.39 ± 0.12, p = 0.013 between groups). No age dependence of MPOD (r = -0.14, p = 0.19) was found in the healthy control group. In the AMD group, however, MPOD declined with age (r = -0.24, p = 0.019). CONCLUSIONS: This study indicates that MPOD is reduced in patients with AMD. In addition, the data of this study indicate that MPOD is age dependent in AMD patients, but not in healthy controls. Taken together with data indicating that lutein supplementation increases MPOD, this provides a rationale for supplementation of the macular pigments in patients with AMD, although long-term clinical outcome data are lacking.

Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age-related macular degeneration.

PURPOSE: There is evidence from several large-scale clinical trials that reduced intake of lutein, a major component of the macular pigment, is a risk factor for the development of AMD. In the present study (LISA; Lutein Intervention Study Austria) it was hypothesized that lutein supplementation increases macular pigment optical density (MPOD). In addition, an investigation was conducted into whether lutein supplementation improves visual acuity (VA) and macular function (mean differential light threshold; MDLT), as assessed with microperimetry. METHODS: One hundred twenty-six patients with AMD (AREDS [Age-related Eye Disease Study] stages 2, 3, and 4) were included in this randomized (2:1), placebo-controlled, double-masked parallel group study. Lutein or placebo was administered for 6 months. MPOD was measured with a custom-built reflectometer. VA was assessed with ETDRS (Early Treatment Diabetic Retinopathy Study) charts, and MDLT was assessed with a microperimeter. RESULTS: Lutein significantly increased MPOD by 27.9% ± 2.9% (P < 0.001 versus placebo). No significant effect of lutein supplementation on MDLT or VA was seen, although a tendency toward an increase was seen for both parameters (MDLT, P = 0.096 versus placebo; VA, P = 0.070 versus placebo). A significant correlation was found, however, between the increase in MPOD after 6 months and the increase in MDLT after 6 months (r = 0.25, P = 0.027), as well as between the increase in MPOD after 6 months and the increase in VA after 6 months (r = 0.27, P = 0.013). CONCLUSIONS: The present study demonstrates that lutein supplementation increases MPOD, as assessed with an objective METHOD: The correlation between the change in MPOD and the change in VA and MDLT indicates that patients who show a pronounced increase in MPOD also benefit in terms of visual function. (ClinicalTrials.gov number, NCT00879671.).