Repeatability of biometry in patients with meibomian gland dysfunction before and after vectored thermal pulsation therapy: A randomized, controlled trial.

PURPOSE: To evaluate the effect of vectored thermal pulsation therapy (VTPT) on the repeatability of biometry readings of two different optical biometers in patients with meibomian gland dysfunction (MGD). METHODS: Patients affected by MGD were included in this prospective, randomized, controlled, investigator-masked study. One eye was randomized to VTPT (LipiFlow®, Johnson & Johnson), and the contralateral eye served as a control. Three visits were scheduled at baseline, 2 weeks and 3 months after the treatment. The main outcome parameter of the study was the repeatability of three calculations of emmetropic intraocular lens power (EIOLP) at the 3 months visit as compared to baseline using an optical biometer (IOLMaster® 700, Carl Zeiss Meditec AG). Repeatability of different keratometry values obtained by the optical biometer and a Placido-disc topographer (MS-39®, CSO) served as secondary outcome parameters. RESULTS: Twenty-nine patients were included in the final analysis. While tear film parameters improved in the study eyes, there were no significant differences regarding the repeatability of three EIOLP measurements between baseline and 3-months-visit in both eyes (p > 0.05) and keratometry measurements in both the optical biometer and the Placido-disc topographer. Remarkably, throughout all study visits, there were some outliers regarding the repeatability of measurements. CONCLUSION: While both devices showed high repeatability regarding EIOLP and keratometry, future studies are needed to detect high-risk patients for poor repeatability.

Blue Light Exposure: Ocular Hazards and Prevention-A Narrative Review.

INTRODUCTION: Exposure to blue light has seriously increased in our environment since the arrival of light emitting diodes (LEDs) and, in recent years, the proliferation of digital devices rich in blue light. This raises some questions about its potential deleterious effects on eye health. The aim of this narrative review is to provide an update on the ocular effects of blue light and to discuss the efficiency of methods of protection and prevention against potential blue light-induced ocular injury. METHODS: The search of relevant English articles was conducted in PubMed, Medline, and Google Scholar databases until December 2022. RESULTS: Blue light exposure provokes photochemical reactions in most eye tissues, in particular the cornea, the lens, and the retina. In vitro and in vivo studies have shown that certain exposures to blue light (depending on the wavelength or intensity) can cause temporary or permanent damage to some structures of the eye, especially the retina. However, currently, there is no evidence that screen use and LEDs in normal use are deleterious to the human retina. Regarding protection, there is currently no evidence of a beneficial effect of blue blocking lenses for the prevention of eye diseases, in particular age-related macular degeneration (AMD). In humans, macular pigments (composed of lutein and zeaxanthin) represent a natural protection by filtering blue light, and can be increased through increased intake from foods or food supplements. These nutrients are associated with lower risk for AMD and cataract. Antioxidants such as vitamins C, E, or zinc might also contribute to the prevention of photochemical ocular damage by preventing oxidative stress. CONCLUSION: Currently, there is no evidence that LEDs in normal use at domestic intensity levels or in screen devices are retinotoxic to the human eye. However, the potential toxicity of long-term cumulative exposure and the dose-response effect are currently unknown.

A pilot study to assess the effect of a three-month vitamin supplementation containing L-methylfolate on systemic homocysteine plasma concentrations and retinal blood flow in patients with diabetes.

Purpose: The aim of the present study was to investigate the effect of a three-month dietary supplementation with a methylfolate formulation on homocysteine plasma concentrations and ocular blood flow parameters in patients with diabetes. Methods: Twenty-four patients with diabetes received a dietary supplement (Oculofolin, Aprofol AG, Switzerland) containing 900 µg L­methylfolate (levomefolate calcium or [6S]-5-methyltetrahydrofolic acid, calcium salt), methylcobalamin, and other ingredients for three consecutive months. The patients' plasma homocysteine concentration and retinal blood flow were assessed at baseline and after three months of folate intake. Retinal blood flow was measured using a custom-built dual-beam Doppler optical coherence tomography (OCT) system. In addition, flicker-induced retinal vasodilatation was assessed by means of a commercially available dynamic vessel analyzer (IMEDOS, Jena, Germany). Results: Supplementation was well tolerated by all patients. After three months, plasma homocysteine concentration significantly decreased from 14.2 ± 9.3 to 9.6 ± 6.6 µmol/L (p < 0.001). In addition, a tendency toward an increased total retinal blood flow from 36.8 ± 12.9 to 39.2 ± 10.8 µl/min was observed, but this effect did not reach the level of significance (p = 0.11). Supplementation had no effect on retinal vessel diameter or flicker-induced vasodilatation. Conclusions: The present data show that a three-month intake of a dietary supplement containing methylfolate can significantly reduce blood homocysteine levels in patients with diabetes. This is of importance because higher homocysteine plasma levels have been found to be associated with an increased risk of vascular associated systemic diseases and eye diseases. Whether systemic methylfolate supplementation affects retinal perfusion must be studied in a larger population.

Nonneovascular Age-Related Macular Degeneration.

The discovery of several genetic variants associated with an increased risk for age-related macular degeneration (AMD) has led to a completely new understanding of AMD. In addition to the known modifiable risk factors, genetic risk factors may also help to assess the risk to progress to nonneovascular AMD. Recently published primary studies have indicated that genetic risk analysis may be valuable in the selection of the currently available antioxidant therapy. So far, the best evidence for preventing progression to nonneovascular AMD comes from the Age-Related Eye Disease Studies (AREDS) I and II. These studies indicate that high doses of antioxidants can reduce the risk of progression to the advanced form of the disease. However, the recent evaluation of the addition of either lutein and zeaxanthin, or ω-3 long-chain polyunsaturated fatty acids, or both, to the established AREDS I formulation did not significantly reduce the risk of developing advanced AMD. There is clearly a large unmet medical need for new therapeutic options for nonneovascular AMD. The modulation of the complement cascade is - despite initially disappointing outcomes obtained with blocking complement factor 5 - currently the most promising approach to the treatment of nonneovascular AMD.

Nutritional supplements in age-related macular degeneration.

Age-related macular degeneration (AMD) is the most frequent cause of blindness in the Western World. While with new therapies that are directed towards vascular endothelial growth factor (VEGF), a potentially efficient treatment option for the wet form of the disease has been introduced, a therapeutic regimen for dry AMD is still lacking. There is evidence from several studies that oral intake of supplements is beneficial in preventing progression of the disease. Several formulations of micronutrients are currently available. The present review focuses on the role of supplements in the treatment and prevention of AMD and sums up the current knowledge about the most frequently used micronutrients. In addition, regulatory issues are discussed, and future directions for the role of supplementation in AMD are highlighted.

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.).

Retinal hemodynamic effects of antioxidant supplementation in an endotoxin-induced model of oxidative stress in humans.

PURPOSE: The Age-Related Eye Disease Study 1 (AREDS 1) has shown that nutritional supplementation with antioxidants and zinc modifies the natural course of AMD. It is presumed that the supplements exert their beneficial effects by ameliorating oxidative stress due to the scavenging of reactive oxygen species (ROS). We have shown in a human model that under oxidative stress induced by administration of lipopolysaccharide (LPS) the vasoconstrictor response of retinal vessels to oxygen breathing is diminished. This reduced vascular response to hyperoxia was previously shown to be normalized by the AREDS 1 supplements. In the present study, we tested the hypothesis that the response can also be restored by a different antioxidant formulation. METHODS: This randomized, double-masked, placebo-controlled parallel group study included 40 healthy volunteers. On each study day, retinal red blood cell (RBC) flow and the reactivity of retinal RBC flow to hyperoxia were investigated in the absence and presence of 2 ng/kg LPS. Between the two study days, subjects received either the supplement or placebo for 14 days. RESULTS: Before supplementation LPS reduced retinal arterial vasoconstriction (P < 0.001) and reactivity of retinal RBC flow (P = 0.03) in response to 100% oxygen breathing. Two weeks of supplementation did not affect baseline retinal RBC flow, but normalized the LPS-induced change in the response to hyperoxia. The arterial vasoconstrictor response during LPS and 100% oxygen breathing was 4.1 ± 1.0% after administration of placebo and 10.6 ± 0.9% after supplementation (P = 0.005). The response of RBC flow to 100% oxygen breathing during LPS was 52.2 ± 2.1% after administration of placebo and 59.5 ± 2.0% after supplementation (P = 0.033). CONCLUSIONS: Our data show that the supplement used in the present study can normalize the response of retinal RBC flow to hyperoxia under LPS administration. This indicates that supplementation can prevent endothelial dysfunction induced by oxidative stress, which is assumed to play a role in the pathophysiology of AMD. (ClinicalTrials.gov number, NCT00914576.).

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.

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.

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.).

Effects of antioxidants (AREDS medication) on ocular blood flow and endothelial function in an endotoxin-induced model of oxidative stress in humans.

PURPOSE: The Age-Related Eye Disease Study (AREDS) has shown that supplementation of antioxidants slows the progression of age-related macular degeneration (AMD). The mechanism underlying this therapeutic effect may be related to a reduction of reactive oxygen species (ROS). The authors have recently introduced a model showing that the response of retinal blood flow (RBF) to hyperoxia is diminished by administration of lipopolysaccharide (LPS). In the present study, the hypothesis was that this response can be restored by the AREDS medication. METHODS: Twenty-one healthy volunteers were included in this randomized, double-masked, placebo-controlled, parallel group study. On each study day, RBF and the reactivity of RBF to hyperoxia were investigated before and after infusion of 2 ng/kg LPS. Between the two study days, subjects took either the AREDS medication or placebo for 14 days. RESULTS: After administration of LPS reduced retinal arterial vasoconstriction during hyperoxia (AREDS group: 12.5% +/- 4.8% pre-LPS vs. 9.4% +/- 4.6% post-LPS; placebo group: 9.2% +/- 3.3% pre-LPS vs. 7.1% +/- 3.5% post-LPS) and a reduced reactivity of RBF during hyperoxia (AREDS: 50.4% +/- 8.9% vs. 44.9% +/- 11.6%, placebo: 54.2% +/- 8.6% vs. 46.0% +/- 6.9%) was found. The reduced responses were normalized after 2 weeks of AREDS antioxidants but not after placebo (vasoconstriction: 13.1% +/- 4.5% vs. 13.1% +/- 5.0% AREDS, 11.2% +/- 4.2 vs. 7.4% +/- 4.2% placebo; RBF: 52.8% +/- 10.5% vs. 52.4% +/- 10.5% AREDS, 52.4% +/- 9.3% vs. 44.2% +/- 6.3% placebo). CONCLUSIONS: The sustained retinal vascular reaction to hyperoxia after LPS in the AREDS group indicates that antioxidants reduce oxidative stress-induced endothelial dysfunction, possibly by eliminating ROS. The model may be an attractive approach to studying the antioxidative capacity of dietary supplements for the treatment of AMD (ClinicalTrials.gov number, NCT00431691).

Influence of infusion volume on the ocular hemodynamic effects of peribulbar anesthesia.

PURPOSE: To test the hypothesis that ocular blood-flow response to peribulbar anesthesia can be reduced by using a smaller volume of anesthetic mixture. SETTING: Departments of Ophthalmology and Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. METHODS: Twenty patients scheduled for bilateral age-related cataract surgery were enrolled in a prospective randomized balanced observer-masked crossover study. Two study days with a 2 mL injection volume or 5 mL injection volume used for peribulbar anesthesia were scheduled. On 1 study day, patients received the 1-dose regimen and on the other study day, when the contralateral eye had surgery, patients received the other injection volume. On both study days, the anesthetic mixture consisted of an equal amount of lidocaine, bupivacaine, and hyaluronidase independently of the injection volume. Intraocular pressure (IOP), blood pressure, and pulse rate were measured noninvasively. Ocular fundus pulsation amplitude (FPA) and peak systolic and end diastolic flow velocities in the central retinal artery were measured with laser interferometry and color Doppler imaging, respectively. The results were recorded as means +/- SD. RESULTS: Peribulbar anesthesia increased IOP and reduced FPA and flow velocities in the central retinal artery. The effects on IOP (5 mL, 35.1% +/- 16.0%; 2 mL, 14.1% +/- 14.1%; P<.001) and ocular hemodynamic parameters (FPA: 5 mL, -17.5% +/- 7.8%/2 mL, -7.3% +/- 7.2%, P<.001; peak systolic velocity: 5 mL, -19.5% +/- 10.7%/2 mL, -10.6% +/- 9.8%, P = .013; end diastolic velocity: 5 mL, -16.7% +/- 6.2%/2 mL, -8.4% +/- 7.3%, P = .005) were more pronounced with the 5 mL injection volume than with the 2 mL injection volume. CONCLUSIONS: An injection volume of 2 mL instead of 5 mL reduced the ocular blood-flow response to peribulbar anesthesia. This procedure may be used in patients with ocular vascular disease to reduce the incidence of anesthesia-induced ischemia and loss of vision.