To investigate whether macular pigment optical density (MPOD) is related to dark adaptation in healthy subjects.

Purpose To study abnormal dark adaptation (DA) in aging and macular degeneration (AMD) using a new technique that measures DA at two retinal locations by using a dual stimulus. To establish whether there are localized regions of impaired rod function, especially the rate of the rod-mediated recovery (S2) as it has been previously suggested Methods Dual arc-shaped white stimuli were presented on a black CRT monitor at locations 6º and 11º of eccentricity in the inferior visual fiel. Recovery of sensitivity to the two stimuli was measured concurrently using the method of adjustment, following a bleaching exposure of at least 30%. The dynamic range of the CRT was expanded using ND filters. DA curves were obtained after fitting the data by non-linear regression to a seven-parameter model. Three groups of observers (young, older and AMD) were tested to detrmine any differences between them and the effect of the testing location, focusing on parameters α (rod-cone break) and S2 (slope of the post- α phase of rod recovery) Results Both stimuli produced matched cone recovery curves within each group. Comparing groups (young vs. older) and (older vs. AMD), we found significant differences in the two DA parameters studied here. Regarding the AMD group, we found a trend in both parameters to be more affected at 6º than at 11º, however, these differences were not significant Conclusion This technique has shown to be sensitive to detect changes in rod recovery in AMD patients compared to healthy subjects and allows the measurement of DA in two retinal locations simultaneously. It may help in the early diagnosis and monitoring of degenerative diseases of the macula, which are increasingly common

Bartlett et al 1 describe the clinical evaluation of the MPS 9000, which is designed to measure macular pigment optical density (MPOD) under clinical conditions. Their aim was to determine instrument variability (noise). Their conclusion, based on the coefficient of repeatability (COR), is that the instrument cannot reliably detect change less than 0.33 optical density (OD) units. This is poor and much worse than previous reports. There is a substantive literature illustrating the veracity of data generated by this instrument. It would have been helpful if the authors offered some comment on the discrepancy between their data and previous findings. By extracting the raw data from figure 1 in Bartlett et al 1 we have calculated the individual measurements for visits 1 and 2. In four out of 38 measurements, there is a difference of …

It is well known that dark adaptation (DA) becomes slower with age. The underlying cause of this impairment is not well understood but may be related to structural changes in the Bruch?s membrane-Retinal Pigment Epithelium (RPE) complex. We examined the characteristics of abnormal rod kinetics in normal older observers (mean age 57.6, n = 15) and compared this with younger observers (mean age 24.92, n = 15). Thresholds were measured following a minimum of 30% bleach, using a white 1 deg stimulus (1 Hz), presented 11 degrees below fixation on a CRT monitor, expanding its luminance range with ND filters. The effects of stimulus size and repeated bleaching were also examined. The ?S2? region of rod recovery was 0.04 log10 units min-1 (p < 0.001) slower in the older group (0.19 �0.03 log10 units min-1) compared with the younger group (0.23 �0.02 log10 units min-1). Neither repeated bleach, nor stimulus size had any effect on the time constant of ?S2? in healthy observers of both ages. The characteristics of slowed time constant in older eyes are compared with systemic causes of delayed DA and the extent to which older observers? night vision may be improved by modifying diet are considered.

Purpose To monitor photopic and scotopic sensitivity recovery during a one year period of supplementation with lutein (L). Methods A two centred, placebo controlled study of L supplementation was conducted in Maastricht, The Netherlands and Manchester, UK. L capsules (10mg ester), or placebo (P) were taken by AMD patients daily. There were 29 patients in the L group and 31 patients in the P group. Sensitivity recovery functions and MPOD (Macular Pigment Optical Density) were measured at baseline and at 4, 8 and 12 months. MPOD was measured with a flicker-based method. Sensitivity recovery following a bleach was obtained by recording visual thresholds (white 1 deg target, nasal eccentricity 11 deg). Results In the L group, there was a mean increase of MPOD from 0.40 (0.17) at baseline to 0.54 (0.21), at visit 4, SDs in brackets (p< 0.0001). In the P group, MPOD was 0.47 (0.19) at baseline and 0.49 (0.19) at visit 4. The mean rod recovery rate for the L group was 3.1 dB/min (1.08) at baseline that increased to 3.65 (0.31) at visit 4. This was statistically significant (p =0.17). The mean rod recovery rate for the P group was reduced from 3.3 (1.3) to 3.1 (1.35), (NS). The rod recovery time for the L group reduced from 15.9 minutes (7.9) to 14.5 minutes (8.4), NS. In the P group, rod recovery time increased from 14.3 (7.7) to 16.8 minutes (p= 0.021). For cone recovery or rod-cone break time no significant differences between baseline and visit 4 in either the L group or the P group were found. Conclusion Rod-based sensitivity recovery kinetics are improved after the augmentation of MPOD with lutein. In patients in whom there is no increase in MP a significant increase in rod-based sensitivity recovery time can be expected.

Purpose To investigate the effect on spatial vision of enhancing macular pigment (MP) with lutein (L) capsules in patients with early AMD. Methods A randomised, placebo-controlled two-centred, 12 months study of the effects of L supplementation was conducted in Manchester, UK and Maastricht, The Netherlands. L capsules (10mg Ester), or a placebo were taken daily. 35 patients (mean age 73.4 ± 8.2, VA>0.5 logMar) were randomly assigned to either L (lutein, n=19) or P (placebo, n=16) groups. Best corrected Log MAR visual acuities, contrast sensitivities (CS) at 0.5, 2, 4, 8,12 and 16 c/deg, and MP were measured at baseline and on three, four month intervals, after the start of the 12 month supplementation period. MP was measured using a flicker-based technique. Results An increase in the mean MP levels was found for the L group; from 0.35±0.19 to 0.47±0.22 OD units that was statistically significant (p<0.0003) while no change in MP was found for the P group. A mean improvement from 0.23±0.12 (baseline) to 0.16±0.10 (visit 4) was found in the VA of the L group (statistically significant, p= 0.004). In the P group there was a non-significant deterioration in VA from 0.18±0.12 to 0.20±0.12. The mean difference in VA between baseline and visit 4 for the L group was 0.07±0.10 and for the P group was -0.03±0.10 (statistically significant difference, p= 0.004). No statistically significant changes were found in CS at any of the tested spatial frequencies for either of the 2 groups. Conclusion Lutein supplementation over a 12 months period improves MP levels in AMD patients and this corresponds to an overall improvement in VA. No such effect is observed in CS.

We report a series of experiments designed to ensure that Macular Pigment Optical Density (MPOD) measurements obtained with a clinical instrument are not influenced by lens yellowing and ocular media optical density. These effects were determined in six subjects using seven Lee Colour Temperature Correcting filters to simulate changes in the transmittance of the ocular media with age. Calculated simulated age matched the data linking age and optical density reported in the literature, and the MPOD was independent of simulated age. The instrument allows an estimation of MPOD to be made which is based only on a foveal (centre-only) measurement rather than, as is conventional, making a comparison between foveal and peripheral measurements. We assessed the performance of this facility by comparing the centre-only estimate of MPOD with that obtained from both central and peripheral measurements in 5616 eyes. The 95% limits of agreement for the two estimates was 0.13 OD units.

and psychophysical methods of measuring MPOD by comparing MPOD at different eccentricities. A straightforward comparison of absolute values of the Macular Pigment Optical Density (MPOD) obtained with optical and psychophysical methods is difficult. Because of its spatial peakedness, the size of the retinal field probed has a major effect. In the objective technique of spectral fundus reflectance, the MPOD is the average over the retinal field sampled, whereas in the psychophysical heterochromatic flickerphotometry minimizing flicker might be achieved at or near the edge of the test field. A comparison of psychophysical and optical methods for determining the spatial profile of Macular Pigment Tos TJM Berendschot1, Rob LP van der Veen1, Maria Makridaki2, Dave Carden2 & Ian J Murray2

Purpose To evaluate a new clinical method for estimating Macular Pigment Optical Density (MPOD) in large populations. Methods The principle of heterochromatic flicker photometry is used. For a series of green-blue ratios, the modulation is slowly reduced from 60Hz (at 6 Hz/sec). Observers press a button when they detect flicker of a green-blue (530-465nm) temporally modulated target. Repeatability was tested on 11 subjects. Measurements (n=5) were repeated after an interval of at least three days. Healthy subjects (n=22, 22-64 years) were tested with the new method and compared with an established spectral fundus reflectance technique. MPOD spatial profiles (n = 7) were obtained with the new method. MPOD data were collected from 5581 subjects (2435 females and 3146 males) measured in 48 optometric practices in the US. Results The new method has good repeatability (r =0.96, ~12%). The data compare well with retinal reflectometry (r =0.85, p<0.001). The spatial profiles are described by a decaying exponential function (r = 0.99), consistent with previous reports. The mean MPOD of the large data set was 0.33 ± 0.187 which is similar to previous studies. Conclusion The task is relatively easy for naïve and elderly observers. The instrument can be readily operated by non-professional staff under clinical conditions. A further advantage is that there is a real-time graphical output indicating satisfactory progress. The instrument provides fast, reliable, accurate MPOD data. It is ideal for large-scale epidemiological study of the macular pigment and also for every-day use in ophthalmic clinics and offices. Commercial interest

Background The metabolic syndrome (MS) refers to a cluster of risk factors, including central obesity, elevated BP, insulin resistance, and dyslipidemia (DLP) characterized by elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL). MS currently affects 27% of US adults and is associated with increased cardiovascular morbidity and mortality. Aggressive lowering of low-density lipoprotein cholesterol (LDL) is critical in coronary artery disease (CAD) prevention. However, when TG levels are high, as often seen in MS, LDL value cannot be calculated. Non-HDL cholesterol (total cholesterol (TC) - HDL) is a measure of all apo-B containing lipoproteins with high atherogenic potential and is considered as a secondary target for lipid therapy in patients with high TG or MS. The purpose of this study was to determine the association between MS and TC, LDL, and non-HDL. Methods Diagnosis of MS was based on NCEP criteria among 928 outpatients in a public hospital. t-Test was used for comparison of lipid components between those with and without MS. Results Seventy percent of patients were black, 68% female; 53% had MS. Among MS patients, 87% had TG > 150 (mg/dL); 85% low HDL; 63% TC > 200; 64% LDL > 100; 69% non-HDL > 130. The results of statistical analysis are as follows: Conclusions The prevalence of MS is high in this patient population. The prevalence of DLP is high in patients with MS. Besides TG and HDL, only non-HDL, but not TC or LDL, is significantly associated with MS. These results suggest that use of non-HDL as the therapeutic target for lipid management is appropriate in MS patients when LDL is not calculable.

Junctional proteins (cadherins and occludin) are important components of endothelial adherens and tight junctions that are remodeled during inflammation, potentially through transient internalization. Junctional protein displacement from the cell surface could represent an important mechanism to decrease homotypic bonding, allowing transient increases in solute flux. Later recycling of these elements to the cell surface would restore junction competence and barrier. Ca++-switch and exposure to inflammatory mediators promote the internalization of endothelial pan-reactive and VE-cadherins but not occludin which redistributes, but is apparently not remodeled acutely. These internalization events are actin-cytoskeleton and PKC-dependent and can be correlated with simultaneous reciprocal changes in cell-substrate adhesion which may maintain structural integrity during periods of altered microvascular barrier.

Under dark adapted or dim conditions the mammalian visual system is carefully programmed to respond rapidly to the sudden onset of bright lights. This response, called the dazzle reflex, is controlled from sub-cortical structures of the brain. It is known anecdotally that exposure to a bright light when dark adapted induces an instinctive closure of one eye to reduce the pain associated with dazzle. This binocular summation of the dazzle response has not previously been reported. The dazzle reflex can be measured in human subjects by recording the electrical activity from surface electrodes located near the muscles around the eye. In this paper we report an investigation of the apparent binocular summation of the dazzle reflex using this technique. The data reveal a clear difference between monocular and binocular stimulation, with the binocular response being much larger than the monocular response. Furthermore this monocular/binocular difference arises only if the stimulus duration is longer than approximately 1 s. These observations are interpreted in terms of the known physiology of blink mechanisms.