Jens Dawczynski

Retinal venous oxygen saturation increases by flicker light stimulation.

PURPOSE Luminance flicker stimulation of the photoreceptors is known to increase retinal blood flow. Elevated blood velocity was determined using laser Doppler velocimetry, and increased vascular diameters during flicker were observed by measurements with a retinal vessel analyzer. Oxygen supply may be the target of the regulation of retinal blood flow. Thus, the oxygen saturation (SO(2)) in retinal arterioles and venules was investigated along with their diameters. METHODS Dual-wavelength (548 nm and 610 nm) fundus images were taken in 19 healthy volunteers (mean age, 26 ± 2.5 years) before (baseline) and during luminance flicker stimulation (12.5 Hz; modulation depth, 1:25). Retinal vessel SO(2) (dual-wavelength optical oximetry) and diameters (central retinal arterial and venous equivalents [CRAE and CRVE]) were determined. RESULTS CRAEs and CRVEs of 193 ± 20 μm and 228 ± 20 μm at baseline increased statistically significant to a maximum of 202 ± 19 μm (P < 0.0005) and 242 ± 17 μm (P < 0.0005), respectively, under flicker stimulation. Although the arterial SO(2) remained unchanged at 98%-99%, an increase of the venous saturation from 60% ± 5.7% to 64% ± 5.9% (P < 0.0005) was found. CONCLUSIONS In agreement with earlier investigations, the vessel dilation found here indicates an elevation of retinal blood flow by luminance flicker stimulation. This increase of the flow should meet the enhanced metabolic need of the neural retina under a physiological stimulus. The augmentation of venous oxygenation may indicate a higher capillary oxygen concentration, necessary to provide a sufficient diffusion rate of oxygen from the capillaries to the inner retinal tissue.

Abnormal retinal autoregulation is detected by provoked stimulation with flicker light in well-controlled patients with type 1 diabetes without retinopathy.

AIMS Investigation of retinal vasodilation under flickering light is considered a dynamic analysis in contrast to the static analysis of retinal vessel equivalents (mean retinal vessel diameter). We investigated whether dynamic analysis apart from the static one in type 1 diabetic patients without diabetic retinopathy with well-controlled diabetes could lead to additional information regarding retinal autoregulation. METHODS 18 normotensive type 1 diabetic patients without retinopathy and 19 healthy subjects were included. Diameter of retinal vessels was measured with Dynamic Vessel Analyzer. Changes in vasodilation are expressed as percent change over baseline values. RESULTS HbA(1c) was 7.5+/-1.0% in diabetic patients. In arteries, the response to flicker was diminished in diabetic patients compared to healthy volunteers (p<0.023). In patients flicker stimulation increased arterial diameter by +2.7% in contrast to +4.4% in controls. Venous vessel diameter increased by +3.1% in diabetic individuals and by +5.3% in the control group (p<0.002). There were no differences in static analysis between both groups. CONCLUSIONS Diabetic patients without retinopathy with relatively good glycemic control show reduced retinal vasodilation after flicker indicating dysfunction in retinal autoregulation. The use of provocation test in conjunction with static analysis could lead to additional information regarding abnormal retinal autoregulation.

Retinal fluorescence lifetime imaging ophthalmoscopy measures depend on the severity of Alzheimer's disease.

To determine alterations in the retina of patients with Alzheimers disease (AD) by the newly developed technique of fluorescence lifetime imaging ophthalmoscopy (FLIO) in a pilot study.

Retinal Vessel Oxygen Saturation under Flicker Light Stimulation in Patients with Nonproliferative Diabetic Retinopathy

PURPOSE We investigated the response of retinal vessel diameters and oxygen saturation to flicker light stimulation of neuronal activity in patients with diabetic retinopathy. METHODS We included 18 patients with nonproliferative diabetic retinopathy (mean age 62.2 ± 8.3 years, diabetes type 1 in 4 patients and type 2 in 14, hemoglobin A1c 7.7 ± 0.9%, duration of diabetes 24.1 ± 9.3 years) and 20 age-matched healthy controls (age 66.7 ± 10.3 years). Dual wavelength (548 and 610 nm) fundus images were taken before and during luminance flicker stimulation (12.5 Hz, modulation depth > 1:25) for 90 seconds. Diameters (central retinal arterial [CRAE] and venous [CRVE] equivalents) and oxygen saturation (SO(2)) were determined, and averaged for all arterioles and venules in an annular area centered at the optic disk. RESULTS Flicker light increased CRAE, CRVE, and venous SO(2) by 0.6 ± 6.6%, 2.7 ± 6.1%, and 2.0 ± 2.4% (P < 0.05), respectively, in the patients as well as 4.7 ± 8.4% (P < 0.05), 8.7 ± 5.2% (P < 0.05), and 4.2 ± 3.5% (P < 0.05), respectively, in the controls. The arterial SO(2) remained unchanged in both groups. The increase of the venous SO2 correlated significantly (P = 0.027) with that of the CRAE. There was a trend (P = 0.06) for lower increase of the venous SO(2) with higher body mass index. CONCLUSIONS Our results support the thesis of an impaired regulation of oxygen supply to the diabetic retina. Whereas in healthy subjects the stimulation of neuronal activity increases the vascular diameters and, subsequently, the oxygen supply, this increase is reduced in diabetic retinopathy. This may hint at the role of endothelial dysfunction in the etiology of the disease.

Fluorescence lifetime imaging ophthalmoscopy in type 2 diabetic patients who have no signs of diabetic retinopathy

Abstract. The time-resolved autofluorescence of the eye is used for the detection of metabolic alteration in diabetic patients who have no signs of diabetic retinopathy. One eye from 37 phakic and 11 pseudophakic patients with type 2 diabetes, and one eye from 25 phakic and 23 pseudophakic healthy subjects were included in the study. After a three-exponential fit of the decay of autofluorescence, histograms of lifetimes τi, amplitudes αi, and relative contributions Qi were statistically compared between corresponding groups in two spectral channels (490<ch1<560  nm, 560<ch2<700  nm). The change in single fluorophores was estimated by applying the Holm–Bonferroni method and by calculating differences in the sum histograms of lifetimes. Median and mean of the histograms of τ2, τ3, and α3 in ch1 show the greatest differences between phakic diabetic patients and age-matched controls (p<0.000004). The lack of pixels with a τ2 of ∼360  ps, the increased number of pixels with τ2>450  ps, and the shift of τ3 from ∼3000 to 3700 ps in ch1 of diabetic patients when compared with healthy subjects indicate an increased production of free flavin adenine dinucleotide, accumulation of advanced glycation end products (AGE), and, probably, a change from free to protein-bound reduced nicotinamide adenine dinucleotide at the fundus. AGE also accumulated in the crystalline lens.

Increased content of zinc and iron in human cataractous lenses.

The purpose of the study was to examine the zinc and iron content of human lenses in different types of cataract and to investigate the possible influence of diabetes on the zinc and iron content of the lens. Iron and zinc of 57 human lenses (28 corticonuclear cataracts and 29 mature cataracts with a mean age of 70.6±16.1 and 74.7±11.1 yr, 41 nondiabetics and 16 diabetics) were determined by atomic absorption spectroscopy. The zinc content of human lenses was significantly increased in mature cataracts compared to corticonuclear cataracts (0.51±0.33 vs 0.32±0.20 µmol/g dry mass, p=0.012). The iron content of mature cataracts was also higher than in corticonuclear cataracts (0.11±0.09 vs 0.07±0.05 µmol/g dry mass, p=0.071). Furthermore, a significant increase of the lens zinc content could be observed with increasing lens coloration (light brown 0.33±0.17 vs dark brown 0.52±0.35 µmol/g dry mass, p=0.032). Diabetic patients seem to have both increased zinc and iron contents in the lens compared to nondiabetic subjects (zinc: 0.45±0.42 vs 0.40±0.22 µmol/g dry mass; iron: 0.12±0.10 vs 0.08±0.05 µmol/g dry mass). These data suggest a possible influence of the lens zinc and iron content on the development of lens opacification. Especially advanced forms of cataract and dark brown colored lenses show significantly increased zinc and iron content.

Simple and objective method for routine detection of the macular pigment xanthophyll

A new simple method for two-dimensional determination of optical density of macular pigment xanthophyll (ODx) in clinical routine is based on a single blue-reflection fundus image. Individual different vignetting is corrected by a shading function. For its construction, nodes are automatically found in structureless image regions. The influence of stray light in elderly crystalline lenses is compensated by a correction function that depends on age. The reproducibility of parameters in a one-wavelength reflection method determined for three subjects (47, 61, and 78 years old) was: maxODx = 6.3%, meanODx = 4.6%, volume = 6%, and area = 6% already before stray-light correction. ODx was comparable in pseudophakic and in an eye with a crystalline lens of the same 11 subjects after stray-light correction. Significant correlation in ODx was found between the one-wavelength reflection method and the two-wavelength autofluorescence method for pseudophakic and cataract eyes of 19 patients suffering from dry age-related macular degeneration (AMD) (R(2) = 0.855). In pseudophakic eyes, maxODx was significantly lower for dry AMD (n = 45) (ODx = 0.491±0.102 ODU) than in eyes with healthy fundus (n = 22) (ODx = 0.615±0.103 ODU) (p = 0.000033). Also in eyes with crystalline lens, maxODx was lower in AMD (n = 125) (ODx = 0.610±0.093 ODU) than in healthy subjects (n = 45) (ODx = 0.674±0.098 ODU) (p = 0.00019). No dependence on age was found in the pseudophakic eyes both of healthy subjects and AMD patients.

Macular Xanthophylls and ω-3 Long-Chain Polyunsaturated Fatty Acids in Age-Related Macular Degeneration: A Randomized Trial

IMPORTANCE It has been shown that the functionality of the macula lutea depends on the nutritional uptake of lutein and zeaxanthin and that it is inversely associated with the risk of age-related macular degeneration (AMD). Additionally, ω-3 long-chain polyunsaturated fatty acids (LC-PUFAs) may also be protective. OBJECTIVE To investigate the effect of a 12-month intervention with macular xanthophylls and ω-3 LC-PUFAs on xanthophylls and fatty acids in plasma, antioxidant capacity, and optical density of the macular pigment of patients with nonexudative AMD. DESIGN The LUTEGA study was a randomized, double-blind, placebo-controlled, parallel clinical trial that was conducted for 12 months. SETTING University Eye Hospital and Institute of Nutrition, Friedrich Schiller University Jena, Germany. PARTICIPANTS A total of 172 individuals with nonexudative AMD. INTERVENTION Individuals were enrolled and randomly divided as follows: placebo group, group 1 (a capsule containing 10 mg of lutein, 1 mg of zeaxanthin, 100 mg of docosahexaenoic acid, and 30 mg of eicosapentaenoic acid administered each day), and group 2 (same substances but twice the dose used in group 1). One hundred forty-five participants completed the study successfully. MAIN OUTCOME MEASURES Plasma xanthophyll concentrations and fatty acid profiles, optical density of the macular pigment, and antioxidant capacity in plasma (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid [Trolox] equivalent antioxidant capacity and photochemiluminescence). RESULTS The concentrations of the administered carotenoids in plasma as well as the optical density of the macular pigment increased significantly in the groups randomized to receive supplementary macular xanthophylls and ω-3 LC-PUFAs after 1 month of intervention and remained at this level through the end of the study. Use of the double dose resulted in a beneficial alteration of the fatty acid profile in the plasma of patients with AMD in comparison with the dose in group 1. The lipophilic antioxidant capacity in plasma was significantly elevated with the intervention. CONCLUSIONS AND RELEVANCE A supplement containing a fixed combination of lutein, zeaxanthin, and ω-3 LC-PUFAs during 12 months significantly improved plasma antioxidant capacity, circulating macular xanthophyll levels, and the optical density of the macular pigment. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00763659.

Anterior optical coherence tomography: a non-contact technique for anterior chamber evaluation

PurposeTo assess a new non-contact anterior optical coherence tomography (OCT) system for anterior chamber evaluation.MethodsA new commercial 131-nm infrared light anterior OCT system was used for anterior chamber evaluation. Forty-four eyes of 35 subjects (18 normal subjects, 17 subjects with anterior chamber abnormalities) were enrolled in the study.ResultsEyes were divided into those with narrowed, broadened and normal anterior chamber depth. Anterior chamber angle dynamics were assessed in three patients with angle-closure glaucoma and cataract extraction. Anterior OCT was also used for visualization of the anterior chamber (OCT goniometry) in a subject with multiple local anaesthetic allergies with phobia regarding conventional contact gonioscopy.ConclusionsAnterior OCT is a new, easy-to-handle, non-contact technique that allows exact evaluation of anterior chamber parameters such as anterior chamber depth, chamber angle dynamics, corneal curvature and corneal thickness.

Optical Coherence Tomography as a Diagnostic Tool for Retinal Pathologies in Avian Ophthalmology

PURPOSE Optical coherence tomography (OCT) is an established diagnostic tool for retinal pathologies in human eyes and has been adapted to small animal models. However, there have been only a few attempts to use OCT for examination of avian eyes, and little is known about structural details of healthy or pathologically affected retinas in living birds. METHODS We used SD-OCT (high-resolution spectral domain OCT) to investigate eyes of various avian species including birds of prey. The birds were anesthetized by isoflurane application during OCT examination. Eyes of a common buzzard (Buteo buteo) could be used for a comparative analysis of OCT images and histologic/immunohistochemical examinations. RESULTS We investigated 45 wild and domestic birds (25 different species, 40 g-7.7 kg body mass) without and with diverse pathologic indications (e.g., body or head trauma). Animals were generally and ophthalmologically examined, and the diagnostic findings of direct ophthalmoscopy and OCT were compared. The OCT examination revealed an increased number of animals with clinical findings and allowed a detailed assessment of structural changes in retinal and choroidal tissue compared to simple direct ophthalmoscopy. Common findings were retinal and choroidal degeneration, retinal detachment, choroidal schisis, drusen, and drusenoid changes. Histologic and immunohistochemical analysis of retinal tissue confirmed the findings of the OCT examination. CONCLUSIONS Spectral domain OCT of eyes in living birds is applicable and useful as a diagnostic tool in veterinary clinical practices and for vision research in general. Optical coherence tomography improves the quality of the common assessment methods in avian ophthalmology, and expands the diagnostic possibilities with respect to identification and prognosis of diseases. This will be particularly important for hereditary retinal defects, especially of precious breeding individuals, or estimation of treatment success in traumatized wild birds with the aim of release back into the wild.