Rob L. P. van der Veen

Abnormal macular pigment distribution in type 2 idiopathic macular telangiectasia

Purpose: To determine the distribution of macular pigment in type 2 idiopathic macular telangiectasia (IMT). Methods: Twenty-two eyes of 12 patients with type 2 IMT were examined by means of best-corrected visual acuity testing, fundus biomicroscopy, fundus photography, fluorescein angiography, and optical coherence tomography. Macular pigment optical density (MPOD) was assessed using a modified confocal scanning laser ophthalmoscope whereby MPOD was calculated from fundus autofluorescence images acquired at two different excitation wavelengths (488 and 514 nm). The results were verified with a method that provides density maps after digital subtraction of log fundus reflectance maps (four patients) and by means of heterochromatic flicker photometry (four patients). Results: MOPD distribution showed an abnormal pattern for all patients with type 2 IMT. In correspondence to the late-phase hyperfluorescent areas shown by fluorescein angiography, MPOD was reduced in the macular area, while there was preserved MPOD at 5° to 7° eccentricity. Conclusions: The central depletion of macular pigment represents a novel phenotypic characteristic of type 2 IMT. Recording of macular pigment distribution may prove useful in the diagnosis of type 2 IMT and implicates an impaired trafficking or storage of lutein and zeaxanthin in the disease process.

Quantification of reduced macular pigment optical density in the central retina in macular telangiectasia type 2

Recently, a unique distribution, namely a reduction of macular pigment optical density (MPOD) within the central retina with a surrounding ring-like structure of preserved MPOD at about 6 degrees eccentricity was suggested to be a common finding in macular telangiectasia (MacTel) type 2. In order to quantify this reduced MPOD, 28 eyes of 14 patients with MacTel type 2 were investigated by fundus reflectometry and two wavelengths fundus autofluorescence (FAF; at 488 nm and 514 nm). Fundus reflectometry showed a reduced MPOD within the central 4 degrees eccentricity that was most absent temporal to the foveola. At 6 degrees, MP density was not different from normative values. Two wavelengths FAF was in accordance with these findings. Fundus reflectometry also allowed separate determination of lutein and zeaxanthin. The patients with MacTel type 2 showed a disproportionally high zeaxanthin reduction. The study suggests that in MacTel type 2, there might be an inability to accumulate MP in the central retina. This disease might serve as a model to further study abnormalities of MP distribution in retinal disorders and to elucidate the mechanisms of MP deposition in the retina.

Lutein supplementation over a one-year period in early AMD might have a mild beneficial effect on visual acuity: the CLEAR study.

PURPOSE We investigated the effect of daily supplementation with lutein (L) capsules on macular pigment optical density (MPOD) and visual acuity (VA) in patients with early age-related macular degeneration (AMD). METHODS A randomized, double-blind, placebo-controlled, two-center investigation of the effects of L supplementation in early AMD was conducted. The duration of the trial was 12 months. The centers were Manchester, United Kingdom and Maastricht, the Netherlands. L capsules (10 mg Ester) or a placebo (P) were taken daily. There were 72 patients (mean age 70.5 ± 8.7) assigned randomly to either L (n = 36) or P (n = 36) groups. MPOD using a flicker-based technique (MPS9000) and best corrected VA (LogMAR) were measured at the beginning and at 4-month intervals over the duration of the 12-month supplementation period. Blood serum samples were collected to monitor compliance. RESULTS At the end of the trial, an overall increase in the mean MPOD level was found for the L group from 0.38 ± 0.19 to 0.53 ± 0.22 optical density (OD) units. According to a mixed design ANOVA, this was statistically significant (P < 0.001). No change in MPOD was found for the P group. There was no significant change in VA in the L group (n = 36). The P group (n = 36) showed a statistically significant deterioration from 0.05 ± 0.13 to 0.09 ± 0.13 (P < 0.05). When comparing the change in VA over the supplementation period, there was a significant difference between the two groups (P < 0.05). To avoid ceiling effects, 2 subgroups of patients with VA worse than 0.06 at baseline were reanalyzed. In the L subgroup (n = 19) a mean improvement in VA from 0.23 ± 0.12 at baseline to 0.16 ± 0.10 at visit 4 was observed (P < 0.05). In the P subgroup (n = 14), there was a small deterioration from 0.18 ± 0.13 to 0.19 ± 0.12 (P = 0.70). The improvement in VA in the L subgroup was compared to the deterioration in VA in the P group and this effect reached statistical significance (P < 0.05). CONCLUSIONS L supplementation increases MPOD levels in early stage AMD patients. According to the VA measurements, the progress of the disease might be slowed in some patients with augmented levels of MP. (ClinicalTrials.gov number NCT01042860.).

Patients with Sjogren-Larsson syndrome lack macular pigment.

PURPOSE Sjögren-Larsson syndrome (SLS), an autosomal recessive hereditary disorder with congenital ichthyosis, spastic diplegia or tetraplegia, and mental retardation, reveals a characteristic macular dystrophy with intraretinal crystals and foveal pseudocysts. Ophthalmic symptoms in SLS are reduced visual acuity and photophobia. This article reports the deficiency of macular pigment as a novel finding in this peculiar, congenital maculopathy. DESIGN Cross-sectional, observational case study. PARTICIPANTS Patients with clinically and genetically proven SLS. METHODS Besides general ophthalmologic examination, 2 different methods were used, fundus autofluorescence (FAF) and fundus reflectometry with the macular pigment reflectometer (MPR), for measuring macular pigment (MP). MAIN OUTCOME MEASURES Distribution profiles and quantity of MP in eyes of SLS patients. RESULTS Twenty-eight eyes of 14 patients were included. The technique to measure MP depended on the ability of the mentally handicapped patients to cooperate. Fundus autofluorescence images providing qualitative estimates were obtained from 9 eyes of 5 patients, and MPR measures providing quantitative estimates were obtained from 19 eyes of 10 patients. Fundus autofluorescence images of SLS patients lacked the typical attenuation of macular FAF signal expected in normal eyes. Mean foveal MP levels measured by MPR showed significantly lower values in SLS patients (0.10+/-0.07) than in healthy individuals (0.69+/-0.17; P<0.001, Student t test). CONCLUSIONS The group of SLS patients studied here had significantly reduced levels of foveal MP. The crystalline macular dystrophy in SLS seems to be the first known disease with a genetically caused deficiency of MP.

Correspondence between retinal reflectometry and a flicker-based technique in the measurement of macular pigment spatial profiles

A comparison of macular pigment optical density (MPOD) spatial profiles determined by an optical and a psychophysical technique is presented. We measured the right eyes of 19 healthy individuals, using fundus reflectometry at 0, 1, 2, 4, 6, and 8 deg eccentricity; and heterochromatic flicker photometry (HFP) at 0, 0.5, 1, 2, 3, 4, 5, 6, and 7 deg, and a reference point at 8 deg eccentricity. We found a strong correlation between the two techniques. However, the absolute estimates obtained by fundus reflectometry data were higher than by HFP. These differences could partly be explained by the fact that at 8 deg eccentricity the MPOD is not zero, as assumed in HFP. Furthermore, when performing HFP for eccentricities of <1 deg, we had to assume that subjects set flicker thresholds at 0.4 deg horizontal translation when using a 1-deg stimulus. MPOD profiles are very similar for both techniques if, on average, 0.05 DU is added to the HFP data at all eccentricities. An additional correction factor, dependent on the steepness of the MPOD spatial distribution, is required for 0 deg.

The effect of lutein supplementation on blood plasma levels of complement factor D, C5a and C3d.

Lutein is selectively taken up by the primate retina and plays an important role as a filter for harmful blue light and as an antioxidant. Recent studies have shown that lutein has systemic anti-inflammatory properties. Dietary lutein has been associated with reduced circulating levels of inflammatory biomarkers such as CRP and sICAM. Whether lutein also affects activation of the complement system has not yet been addressed and was the purpose of the study described here. Seventy-two subjects with signs of early macular degeneration were randomly assigned to receive either a 10 mg lutein supplement or a placebo during one year. EDTA blood samples were collected at 0, 4, 8 and 12 months. Complement factor D (CFD), a rate limiting component of the alternative pathway of complement activation and the complement activation products C5a and C3d were determined in the plasma samples by ELISA. A significant 0.11 µg/ml monthly decrease in plasma CFD concentration was observed in the lutein group (p<0.001), resulting in a 51% decrease from 2.3 µg/ml at baseline to 1.0 µg/ml at 12 months. The C5a concentration showed a significant 0.063ng/ml monthly decrease in the lutein group (p<0.001) resulting in a 36% decrease from 2.2ng/ml at baseline to 1.6ng/ml at 12 months. The C3d concentration showed a significant 0.19µg/ml monthly decrease in the lutein group (p=0.004) that gave rise to a 9% decrease from 15.4µg/ml at baseline to 14.4µg/ml at 12 months. In the placebo group we found a significant 0.04 µg/ml monthly decrease in plasma CFD concentration, whereas no changes were observed for C5a and C3d. Lutein supplementation markedly decreases circulating levels of the complement factors CFD, C5a and C3d levels, which might allow a simple method to control this inflammatory pathway of the innate immune system.