Retinal oxygen extraction in individuals with type 1 diabetes with no or mild diabetic retinopathy.

AIMS/HYPOTHESIS: The aim of this study was to compare retinal oxygen extraction in individuals with diabetes with no or mild non-proliferative diabetic retinopathy and healthy age- and sex-matched volunteers. METHODS: A total of 24 participants with type 1 diabetes and 24 healthy age- and sex-matched volunteers were included in this cross-sectional study. Retinal oxygen extraction was measured by combining total retinal blood flow measurements using a custom-built bi-directional Doppler optical coherence tomography system with measurements of oxygen saturation using spectroscopic reflectometry. Based on previously published mathematical modelling, the oxygen content in retinal vessels and total retinal oxygen extraction were calculated. RESULTS: Total retinal blood flow was higher in diabetic participants (46.4 ± 7.4 µl/min) than in healthy volunteers (40.4 ± 5.3 µl/min, p = 0.002 between groups). Oxygen content in retinal arteries was comparable between the two groups, but oxygen content in retinal veins was higher in participants with diabetes (0.15 ± 0.02 ml O2/ml) compared with healthy control participants (0.13 ± 0.02 ml O2/ml, p < 0.001). As such, the arteriovenous oxygen difference and total retinal oxygen extraction were reduced in participants with diabetes compared with healthy volunteers (total retinal oxygen extraction 1.40 ± 0.44 vs 1.70 ± 0.47 µl O2/min, respectively, p = 0.03). CONCLUSIONS/INTERPRETATION: Our data indicate early retinal hypoxia in individuals with type 1 diabetes with no or mild diabetic retinopathy as compared with healthy control individuals. Further studies are required to fully understand the potential of the technique in risk stratification and treatment monitoring. TRIAL REGISTRATION: ClinicalTrials.gov NCT01843114.

Optic nerve head blood flow regulation during changes in arterial blood pressure in patients with primary open-angle glaucoma.

PURPOSE: Abnormal autoregulation of optic nerve head blood flow (ONHBF) has been postulated to play an important role in primary open-angle glaucoma (POAG). We used laser Doppler flowmetry (LDF) to estimate quantitatively the ONHBF and compared ONHBF autoregulation between glaucoma patients and healthy controls during isometric exercise. METHODS: Forty patients with POAG and 40 healthy age- and sex-matched subjects underwent three periods of isometric exercise, each consisting of 2 min of handgripping. Optic nerve head blood flow (ONHBF) was measured continuously using LDF. Systemic blood pressure, intraocular pressure and ocular perfusion pressure were assessed in all participants. RESULTS: Isometric exercise was associated with an increase in ocular perfusion pressure during all handgripping periods in both groups (p < 0.001). However, there was no change in ONHBF in either group. Three of the glaucoma patients and two of the healthy subjects showed a consistent 10% decrease in blood flow during isometric exercise, in spite of an increase in their blood pressure. This difference between groups was not significant (p = 0.61). Four other glaucoma subjects showed a consistent increase in blood flow of more than 10% during isometric exercise, whereas this was not seen in healthy subjects (p = 0.035). CONCLUSION: This study suggests that abnormal ONHBF autoregulation is more often seen in patients with POAG than healthy control subjects. The relationship to the glaucoma disease process is currently unknown and requires further investigation.

Assessment of choroidal blood flow using laser speckle flowgraphy.

BACKGROUND/AIMS: There is considerable interest in novel techniques to quantify choroidal blood flow (CBF) in humans. In the present study, we investigated a novel technique to measure CBF based on laser speckle flowgraphy (LSFG) in healthy subjects. METHODS: This study included 31 eyes of 31 healthy, non-smoking subjects aged between 19 and 74 years. A commercial LSFG instrument was used to measure choroidal vessel diameter (CVD) and relative flow volume (RFV) in choroidal vessels that were identified on fundus photos, an approach that was used previously only for retinal vessels. The reproducibility and the effect of isometric exercise on these parameters were investigated. The latter was compared with measurement of subfoveal CBF using laser Doppler flowmetry (LDF). RESULTS: Intraclass correlation coefficients for CVD and RFV were higher than 0.8 indicating excellent reproducibility. During isometric exercise, we observed an increase in ocular perfusion pressure of approximately 60% (P<0.001). The increase in RFV and CBF was lower, but also highly significant versus baseline (at minute 6 of isometric exercise: RFV 10.5%±4.2%, CBF 8.3%±3.6%; P<0.001 each) indicating choroidal autoregulation. CONCLUSION: LSFG may be a novel approach to study blood flow in choroidal vessels. Data are reproducible and show good agreement with LDF data. TRIAL REGISTRATION NUMBER: NCT02102880, Results.

Evaluation of flicker induced hyperemia in the retina and optic nerve head measured by Laser Speckle Flowgraphy.

PURPOSE: The coupling between neural activity and blood flow is a physiological key principle of ocular blood flow regulation. The current study was performed to investigate whether Laser speckle flowgraphy (LSFG), a commercially available technique for measuring blood flow, is capable to assess flicker-induced haemodynamic changes in the retinal and optic nerve head (ONH) circulation. METHODS: Twenty healthy subjects were included in this cross sectional study. A commercial LSFG instrument was used to measure blood flow at the ONH as well as in retinal vessels before and during stimulation with flickering light. Mean blur rate (MBR), a measure of relative blood flow velocity, was obtained for the ONH and relative flow volume (RFV) a measure of relative blood flow of the respective retinal vessels. RESULTS: Stimulation with flicker light increased ONH MBR by +17.5%±6.6% (p<0.01). In retinal arteries, flicker stimulation led an increase of +23.8±10.0% (p<0.05) in total RFV. For retinal veins, an increase of +23.1%±11.0 (p<0.05) in total RFV was observed during stimulation. A higher response was observed in nasal RFV compared to temporal RFV in retinal arteries (nasal: +28.9%±20.0%; temporal: +20.4%±17.6%, p<0.05) and veins (nasal: +28.3%±19.6%; temporal +17.8%±18.9%, p<0.05). CONCLUSION: As shown previously with other techniques, flicker stimulation leads to an increase in retinal and optic nerve head blood flow. Our results indicate that LSFG is an appropriate method for the quantification of retinal and ONH blood flow during visual stimulation and may be used as a non-invasive, easy to use tool to assess neuro-vascular coupling in humans.

Effect of Hyaluronic Acid/Trehalose in Two Different Formulations on Signs and Symptoms in Patients with Moderate to Severe Dry Eye Disease.

PURPOSE: This randomized, observer-masked, crossover study investigated the effect of two hyaluronic acid/trehalose-based containing formulations, with different physical properties, on the signs and symptoms in patients with moderate to severe dry eye disease (DED). METHODS: In one group, patients received a mixture of sodium hyaluronate and trehalose (HT, Thealoz Duo®) for use during the day. In the other group, patients received a more viscous formulation consisting of hyaluronic acid, trehalose, and carbomer (HTC-gel, Thealoz Duo Gel) to use pro re nata. Both groups used HTC-gel before going to bed. Clinical standard tests for DED were performed at the beginning and end of each one-week period. Further, patient satisfaction including quality of sleep was assessed using a visual analogue scale. RESULTS: Corneal fluorescein and conjunctival lissamine green staining scores decreased, and tear breakup time (BUT) increased for both groups (p < 0.001 each). Mean instillation frequency was 3.1 ± 2.6 drops/day when using HT and 1.9 ± 2.2 drops/day when using HTC-gel (p=0.02). A significant improvement in the quality of sleep was observed with both treatments (p=0.01). CONCLUSIONS: Our results show improvement in signs and symptoms of DED in both groups. While instillation of HTC-gel resulted in a lower instillation frequency, both formulations of trehalose showed good clinical efficacy. This trial is registered with NCT02980913.

A Controlled, Randomized Double-Blind Study to Evaluate the Safety and Efficacy of Chitosan-N-Acetylcysteine for the Treatment of Dry Eye Syndrome.

PURPOSE: This study was designed to evaluate the effect of chitosan-N-acetylcysteine (C-NAC) eye drops on tear film thickness (TFT) in patients with dry eye syndrome (DES). METHODS: This was a controlled, randomized, double-blind clinical investigation with patients assigned to 2 cohorts. In Cohort I, 21 patients were randomized to receive 1 instillation of C-NAC eye drops in 1 eye and placebo (normal saline solution) in the contralateral eye. In Cohort II, 17 patients were randomized to receive C-NAC eye drops once (QD) or twice (BID) daily for 5 days. TFT was assessed with a custom-built ultrahigh-resolution optical coherence tomography system. RESULTS: In Cohort I, mean TFT increased from 3.9 ± 0.5 µm predose to 4.8 ± 1.1 µm 10 min postdose after treatment with C-NAC. The increase was significantly different from placebo over time (P < 0.0001) and remained stable until 24 h postdose. In Cohort II, TFT increased with QD and BID instillation, with no significant difference between regimens. In both groups, Ocular Surface Disease Index scores improved, fewer patients presented with corneal damage, and symptoms of ocular discomfort/conjunctival redness were reduced. CONCLUSIONS: A single instillation of C-NAC significantly increased mean TFT in patients with DES as early as 10 min after instillation and lasted for 24 h. The magnitude of the increase in TFT following a single instillation was comparable with that after instillation twice daily over 5 days. Corneal damage improved in >60% of patients. C-NAC could be a viable treatment option for DES.

Optic nerve head and retinal blood flow regulation during isometric exercise as assessed with laser speckle flowgraphy.

The aim of the present study was to investigate regulation of blood flow (BF) in the optic nerve head (ONH) and a peripapillary region (PPR) during an isometric exercise-induced increase in ocular perfusion pressure (OPP) using laser speckle flowgraphy (LSFG) in healthy subjects. For this purpose, a total of 27 subjects was included in this study. Mean blur rate in tissue (MT) was measured in the ONH and in a PPR as well as relative flow volume (RFV) in retinal arteries (ART) and veins (VEIN) using LSFG. All participants performed isometric exercise for 6 minutes during which MT and mean arterial pressure were measured every minute. From these data OPP and pressure/flow curves were calculated. Isometric exercise increased OPP, MTONH and MTPRR. The relative increase in OPP (78.5 ± 19.8%) was more pronounced than the increase in BF parameters (MTONH: 18.1 ± 7.7%, MTPRR: 21.1 ± 8.3%, RFVART: 16.5 ±12.0%, RFVVEIN: 17.7 ± 12.4%) indicating for an autoregulatory response of the vasculature. The pressure/flow curves show that MTONH, MTPRR, RFVART, RFVVEIN started to increase at OPP levels of 51.2 ± 2.0%, 58.1 ± 2.4%, 45.6 ± 1.9% and 45.6 ± 1.9% above baseline. These data indicate that ONHBF starts to increase at levels of approx. 50% increase in OPP: This is slightly lower than the values we previously reported from LDF data. Signals from the PPR may have input from both, the retina and the choroid, but the relative contribution is unknown. In addition, retinal BF appears to increase at slightly lower OPP values of approximately 45%. LSFG may be used to study ONH autoregulation in diseases such as glaucoma. TRIAL REGISTRATION: ClinicalTrials.gov NCT02102880.

Effect of different lubricant eye gels on tear film thickness as measured with ultrahigh-resolution optical coherence tomography.

PURPOSE: To compare the effect of a single drop of different lubricant eye gels on tear film thickness (TFT) as measured with ultrahigh-resolution optical coherence tomography (UHR-OCT) in patients with mild-to-moderate dry eye disease (DED). METHODS: The study followed a randomized, single-masked, observer-blinded parallel group design. Patients received a single dose of either unpreserved trehalose 3% + hyaluronic acid 0.15% (TH), hyaluronic acid 0.2% (HA) or polyethylene glycol 0.4% + propylene glycol 0.3% (PP) eye drops. In total, 60 patients were included and TFT was measured using a custom-built UHR-OCT system. RESULTS: The mean TFT at baseline was 3.5 ± 0.7 µm. There was a significant difference in the time-course of TFT between the three groups (p = 0.001 between groups). Ten minutes after instillation, TFT increased by 155.8 ± 86.6%, 65.7 ± 71.5% and 33.4 ± 19.6% in the PP, TH and HA group, respectively (p < 0.001 between groups). Thirty minutes after instillation, the effect of all three different agents on TFT was comparable. Sixty and 120 min after administration, a significant increase in TFT was only seen for the TH group, but not for the other products (60 min: p < 0.021 between groups; 120 min: p < 0.037 between groups). CONCLUSION: In conclusion, we observed differences in TFT after administration of the lubricant gels. Ten minutes after instillation, a pronounced increase in TFT was observed in all groups. As compared to the other products, the combination of trehalose 3% + hyaluronic acid 0.15% offers a significantly longer increase in TFT indicating for a longer residence time.

Factors Associated With Choroidal Blood Flow Regulation in Healthy Young Subjects.

PURPOSE: To analyze regulation of subfoveal choroidal blood flow (FLOW) during isometric exercise in healthy subjects in dependence of intraocular pressure (IOP), mean arterial pressure (MAP), ocular perfusion pressure (OPP), age, sex, fasting glucose, cholesterol, triglycerides, creatinine, and C-reactive protein levels and hematocrit. METHODS: We retrospectively analyzed results obtained in 261 healthy subjects who underwent a period of 6 minutes of isometric exercise during which FLOW was measured continuously and MAP was measured every minute. From these data, OPP and choroidal pressure/flow curves were calculated. Subjects were grouped into tertiles with regard to the dependent variables, and pressure/flow relationships were compared. RESULTS: Choroidal blood flow started to increase at OPP values of approximately 65% dependent on the MAP/IOP tertile. A significant increase of FLOW from baseline was noted at 67.7 ± 2.1% in the lowest MAP tertile, at 67.7 ± 2.0% in the second MAP tertile, and at 61.8 ± 2.0% in the highest MAP tertile (P = 0.01). At the three IOP levels, FLOW started to increase at an OPP increase of 69.8 ± 2.1%, 70.1 ± 2.2%, and 65.4 ± 1.9% above baseline, respectively (P = 0.03). Choroidal pressure/flow curves were independent of the other variables. CONCLUSIONS: The present analysis indicates that FLOW regulation during isometric exercise is dependent on absolute MAP as well as IOP levels. This indicates that regulation depends on pressure levels at both the arterial and the venous side of the choroidal circulation and highlights the complexity of FLOW regulation during changes in OPP that cannot be simply characterized by classical autoregulation models.

Factors Determining Flicker-Induced Retinal Vasodilation in Healthy Subjects.

PURPOSE: The purpose of this study was to analyze factors determining retinal arterial and venous responses to stimulation with diffuse luminance flicker in healthy subjects. METHODS: We retrospectively analyzed results obtained in 374 healthy subjects who had previously participated in clinical studies in our department. A total of 153 subjects underwent a protocol in which flicker stimulation was delivered through the fundus camera at 8 Hz (protocol 1), separating measurement and stimulation light depending on the wavelength, and 221 subjects underwent a protocol in which diffuse luminance flicker was delivered at 12.5 Hz with high modulation depth (protocol 2). We investigated whether sex, systemic blood pressure, baseline vessel size, blood plasma concentration of fasting glucose and hematocrit, and serum concentration of cholesterol, triglycerides, creatinine and C-reactive protein influenced the retinal vascular response to flicker stimulation. RESULTS: Flicker responses in arteries and veins were more pronounced in protocol 2 than in protocol 1 (P < 0.001, each). In both of the protocols the vascular response to stimulation with diffuse luminance flicker was larger in smaller vessels (P between 0.001 and 0.016). In protocol 2 the retinal arterial flicker response was negatively associated with cholesterol serum levels (P = 0.033); in protocol 1, only a tendency toward this effect was observed (P = 0.056). CONCLUSIONS: The present analysis indicates that retinal arterial and venous responses to stimulation with diffuse luminance flicker depend on the way the stimulation is delivered through the fundus camera. In addition, the flicker response varied with vessel size, that is, the smaller the vessel width, the larger the flicker response. Finally, our data indicate that, even within the normal range, higher cholesterol serum levels are associated with lower hyperemic flicker responses.

Ocular Blood Flow Measurements in Healthy White Subjects Using Laser Speckle Flowgraphy.

PURPOSE: To assess the feasibility and reliability of Laser Speckle Flowgraphy (LSFG) to measure ocular perfusion in a sample of healthy white subjects and to elucidate the age-dependence of the parameters obtained. METHODS: This cross-sectional study included 80 eyes of 80 healthy, non-smoking white subjects of Western European descent between 19 and 79 years of age. A commercial LSFG instrument was applied to measure ocular blood flow at the optic nerve head (ONH) three successive times before and after pharmacological pupil dilation. The mean blur rate (MBR), a measure of relative blood flow velocity, was obtained for different regions of the ONH. Eight parameters of ocular perfusion derived from the pulse-waveform analysis of MBR including blowout time (BOT) and falling rate (FR) were also recorded. RESULTS: Artifact-free LSFG images meeting the quality criteria for automated image analysis were obtainable in 93.8% without pupil dilation and in 98.8% with pharmacological pupil dilation. Measurements of MBR showed excellent repeatability with intraclass correlation coefficients ≥ 0.937 and were barely affected by pupil dilation. The majority of pulse-waveform derived variables exhibited equally high repeatability. MBR-related blood flow indices exhibited significant age dependence (p<0.001). FR (r = 0.747, p<0.001) and BOT (r = -0.714, p<0.001) most strongly correlated with age. CONCLUSIONS: LSFG represents a reliable method for the quantitative assessment of ocular blood flow in white subjects. Our data affirms that the LSFG-derived variables FR and BOT may be useful biomarkers for age-related changes in ocular perfusion.

Measurements of Retinal Perfusion Using Laser Speckle Flowgraphy and Doppler Optical Coherence Tomography.

PURPOSE: This study evaluated the validity of retinal perfusion measurements using laser speckle flowgraphy (LSFG) by means of in vitro experiments and direct comparison with dual-beam Doppler optical coherence tomography (D-OCT) in a healthy Caucasian population. METHODS: The flow velocity of scattering solution pumped through a glass capillary was measured at 17 different flow velocities (range, 0.5-47 mm/s) using LSFG. The flow within the glass capillary was produced by a computer-controlled infusion pump. In vivo, three consecutive LSFG scans were obtained in 20 eyes of 20 healthy Caucasian subjects before and after pharmacological pupil dilation. Relative flow volume (RFV), the primary output parameter of LSFG, was comparatively validated relative to absolute measurements of retinal blood flow and velocity as obtained from D-OCT. RESULTS: In the in vitro experiments, RFV was found to saturate at a level of approximately 700 arbitrary units (au) or 23.5 mm/s of actual velocity. In vivo, RFV was in significant agreement with absolute blood flow measurements as obtained from D-OCT in arteries (r = 0.69, P = 0.001) and veins (r = 0.74, P < 0.001). However, linear regression analysis revealed significant positive zero offset values for RFV of 223.4 and 282.7 au in arteries and veins, respectively. CONCLUSIONS: Measurements of RFV were successfully obtainable, reproducible, and not influenced by pharmacological pupil dilation. Nevertheless, our data revealed flaws in the LSFG method of measuring retinal perfusion in Caucasians. Adjustment to the technique is required to address apparent issues with RFV, especially saturation effects with higher arterial flow rates. The present dataset may provide a valuable tool to do so. (Clinicaltrials.gov number NCT02582411).

Effect of a Matrix Therapy Agent on Corneal Epithelial Healing After Standard Collagen Cross-linking in Patients With Keratoconus: A Randomized Clinical Trial.

IMPORTANCE: Corneal abrasions are frequent after standard (epithelium-off [epi-off]) corneal collagen cross-linking (CXL) in patients with progressive keratoconus. A new matrix therapy agent (ReGeneraTing Agent [RGTA]) has been developed to promote corneal wound healing. OBJECTIVE: To assess the effect of the new type of matrix therapy agent on corneal wound healing after epi-off CXL in patients with keratoconus. DESIGN, SETTING, AND PARTICIPANTS: This double-masked randomized clinical trial enrolled 40 patients with keratoconus undergoing epi-off CXL from July 18, 2014, to October 21, 2015, when the last follow-up was completed. The analysis of the intention-to-treat population was performed at the Department of Clinical Pharmacology in cooperation with the Center for Medical Physics and Biomedical Engineering and the Department of Ophthalmology and Optometry of the Medical University of Vienna. INTERVENTIONS: Patients were randomized to receive the matrix therapy agent or hyaluronic acid-containing eyedrops, 0.1%, every other day starting immediately after surgery. The size of the corneal defect was measured using ultrahigh-resolution optical coherence tomography (OCT) and slitlamp photography (SLP) with fluorescein staining. MAIN OUTCOMES AND MEASURES: Corneal wound healing rate, defined as the size of the defect over time. RESULTS: Among the 40 patients undergoing epi-off CXL (31 men; 9 women; mean [SD] age, 31 [10] years), wound healing was significantly faster in the matrix therapy agent group compared with the hyaluronic acid group (4.4 vs 6.1 days; mean difference, 1.7 days; 95% CI, 0.25-3.15 days; P = .008). The defect size was smaller in the matrix therapy agent group than in the hyaluronic acid group as measured with OCT (12.4 vs 23.9 mm2; mean difference, 11.6 mm2; 95% CI, 0.8-23.5 mm2; P = .045) and SLP (11.9 vs 23.5 mm2; mean difference, 11. 6 mm2; 95% CI, 1.3-22.9 mm2; P = .03). A correlation between the defect size measured with OCT and SLP was found (r = 0.89; P < .001). No ocular or serious adverse events occurred. CONCLUSIONS AND RELEVANCE: Use of a new matrix therapy agent appears to improve corneal wound healing after CXL in patients with keratoconus. Monitoring of corneal wound healing using ultrahigh-resolution OCT might be an attractive alternative to SLP because OCT provides an objective and 3-dimensional evaluation of the corneal defect. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02119039.

Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease.

PURPOSE: This study was designed to investigate the effect of a single-drop instillation of different lacrimal substitutes on tear film thickness (TFT) assessed with optical coherence tomography in patients with mild to moderate dry eye disease. METHODS: The study was performed in a randomized, double-masked, controlled parallel group design. Patients received a single dose of either unpreserved trehalose 30 mg/mL and sodium hyaluronate 1.5 mg/mL (TH-SH, Thealoz Duo), unpreserved sodium hyaluronate, 0.15% (HA, Hyabak) or sodium chloride, 0.9% (NaCl, Hydrabak) eye drops. Sixty patients finished the study according to the protocol. TFT was measured with a custom-built ultrahigh-resolution Fourier domain optical coherence tomography system providing a resolution of 1.2 µm. RESULTS: The mean TFT before treatment was 2.5 ± 0.4 µm. Ten minutes after instillation, TFT significantly increased in the TH-SH group from 2.4 ± 0.4 to 3.1 ± 0.9 µm (P < 0.01) and in the HA group from 2.4 ± 0.3 to 2.9 ± 0.5 µm (P < 0.01), whereas no significant change was observed in the NaCl group (from 2.6 ± 0.4 to 2.7 ± 0.4 µm, P = 0.76). The increase in TFT remained statistically significant up to 240 minutes after administration of TH-SH. In contrast, the increase in TFT after administration of HA was only statistically significant at 10, 20, and 40 minutes after drop instillation. CONCLUSIONS: The findings of this study indicate that single instillation of TH-SH and HA eye drops increases TFT in patients with dry eye disease. The data also indicate longer corneal residence of the TH-containing eye drops. The effect of multiple instillation and long-term use of artificial tears on TFT warrants further investigation.

Effect of hyaluronic acid on tear film thickness as assessed with ultra-high resolution optical coherence tomography.

PURPOSE: The aim of this study was to assess the effect of a single drop of hyaluronic acid on tear film thickness (TFT) in healthy subjects. METHODS: Sixteen healthy subjects (eight male/eight female) aged between 20 and 36 years were included in this randomized, double-masked placebo-controlled study. One eye received a single dose of hyaluronic acid (Olixia pure(®) ; Croma Pharma, Korneuburg, Austria) eye drops, and the fellow eye received physiologic saline solution as placebo control. The study eye was chosen randomly. TFT as measured with a custom-built Fourier-domain optical coherence tomography (FD-OCT) system was the main outcome variable and measured before and every 10 min until 1 hr after topical administration. RESULTS: Baseline TFT was 4.8 ± 0.5 µm in the study eye and 5.0 ± 0.4 µm in the control eyes. Hyaluronic acid significantly increased TFT (p = 0.008 versus placebo) with a maximum effect 10 min after instillation (13.9 ± 11.9%). Post hoc analysis revealed that an increase in TFT was seen until 30 min after administration compared to placebo. Data in the placebo group show high reproducibility with an intraclass correlation coefficient of 0.93 and a coefficient of variation of 5.4 ± 3.3%. CONCLUSION: The data of this study indicate that hyaluronic acid increases TFT for as long as 30 min in healthy subjects. In addition, our data provide evidence that our custom-built OCT system is capable of measuring residence time of lubricants on the ocular surface.

Antioxidative capacity of a dietary supplement on retinal hemodynamic function in a human lipopolysaccharide (LPS) model.

PURPOSE: Beneficial effects of dietary supplements in age-related macular degeneration (AMD) are related to antioxidative properties. In the Age-Related Eye Disease Study 1 (AREDS 1), a reduced progression to late stage AMD was found using vitamin C, E, zinc, and ß-carotene. We showed previously that the AREDS 1 formulation restores the O2-induced retinal vasoconstrictor response of retinal vessels in a human endotoxin (lipopolysaccharide [LPS]) model. METHODS: We hypothesized that the abnormal O2-induced retinal red blood cell (RBC) flow response can be modulated by a different formulation (vitamin C, E, and zinc, lutein/zeaxanthin, selenium, taurine, Aronia extract, and omega-3 free fatty acids). A total of 43 healthy subjects was included in this randomized, double masked, placebo-controlled parallel group study. The reactivity of retinal arterial and venous diameter, RBC velocity, and flow to 100% O2 breathing was investigated in the absence and presence of 2 ng/kg LPS. Between the two study days was a 14-day period of daily dietary supplement intake. RESULTS: The decrease in retinal arterial diameter, RBC velocity, and flow during 100% O2 breathing was diminished significantly after LPS infusion. Dietary supplement intake for 14 days almost restored the response of retinal hemodynamic parameters to 100% O2 after LPS administration. This effect was significant for retinal arterial diameter (P = 0.03 between groups), and RBC velocity and flow (each P < 0.01 between groups). CONCLUSIONS: The present data indicate restoring of the RBC flow response to 100% O2 after LPS administration. This is likely due to an amelioration of endothelial dysfunction resulting from oxidative stress, a factor involved in AMD pathophysiology. (ClinicalTrials.gov number, NCT00914576.).