ABNORMAL RETINAL REFLECTIVITY TO SHORT-WAVELENGTH LIGHT IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA.

PURPOSE: Macular telangiectasia Type 2 (MacTel) is a bilateral, progressive, potentially blinding retinal disease characterized by vascular and neurodegenerative signs, including an increased parafoveal reflectivity to blue light. Our aim was to investigate the relationship of this sign with other signs of macular telangiectasia Type 2 in multiple imaging modalities. METHODS: Participants were selected from the MacTel Type 2 study, based on a confirmed diagnosis and the availability of images. The extent of signs in blue-light reflectance, fluorescein angiographic, optical coherence tomographic, and single- and dual-wavelength autofluorescence images were analyzed. RESULTS: A well-defined abnormality of the perifovea is demonstrated by dual-wavelength autofluorescence and blue-light reflectance in early disease. The agreement in area size of the abnormalities in dual-wavelength autofluorescence and in blue-light reflectance images was excellent: for right eyes: ρ = 0.917 (P < 0.0001, 95% confidence interval 0.855-0.954, n = 46) and for left eyes: ρ = 0.952 (P < 0.0001, 95% confidence interval 0.916-0.973, n = 49). Other changes are less extensive initially and expand later to occupy that area and do not extend beyond it. CONCLUSION: Our findings indicate that abnormal metabolic handling of luteal pigment and physical changes giving rise to increased reflectance are widespread in the macula throughout the natural history of the disease, precede other changes, and are relevant to early diagnosis.

CORRELATION OF OPTICAL COHERENCE TOMOGRAPHY AND MACULAR PIGMENT OPTICAL DENSITY MEASUREMENTS IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA.

PURPOSE: Macular telangiectasia is associated with neurodegenerative changes including focal outer retinal atrophy and a loss of macular pigment (MP). We aimed to investigate whether an association between spectral domain optical coherence tomography neurodegenerative signs and MP abnormalities can be detected. METHODS: Forty-seven eyes of 27 macular telangiectasia Type 2 patients (mean age 66.7 years, range 50-82 years, 12 male) were investigated. An MP pattern was recorded using a dual-wavelength autofluorescence method and classified according to severity (I-III). Outer plexiform, inner nuclear, and photoreceptor layer thickness values were measured in Spectralis spectral domain optical coherence tomography scans. Thickness values were compared with those of a control group of 14 healthy age-matched eyes. RESULTS: Macular pigment redistribution was found to be Class I in 11 eyes, Class II in 28 eyes, and Class III in 8 eyes. More advanced stages of MP loss were associated with a greater, statistically significant thinning of the outer plexiform and inner nuclear layer complex and photoreceptor layers (P ≤ 0.001). Lower absolute levels of MP were also associated with a thinning of the photoreceptor layer. Thinning was restricted to within the parafovea, more severe at temporal eccentricities. CONCLUSION: Our findings support the hypothesis that in macular telangiectasia Type 2 cellular degenerative processes leading to a thinning of these layers also result in reduction and redistribution of MP.

ASSOCIATION BETWEEN CHANGES IN MACULAR VASCULATURE IN OPTICAL COHERENCE TOMOGRAPHY- AND FLUORESCEIN- ANGIOGRAPHY AND DISTRIBUTION OF MACULAR PIGMENT IN TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA.

PURPOSE: We investigate the association between morphologic findings in optical coherence tomography angiography (OCTA) as a new method offering the visualization of deeper layers of retinal vasculature and fluorescein angiography (FA) and macular pigment imaging and in Type 2 macular telangiectasia. METHODS: Fourty-two eyes of 21 patients with macular telangiectasia (38-68 years, 14 female) were examined by FA and OCTA and 24 eyes additionally with dual-wavelength autofluorescence. Early and late FA, macular pigment density images, and (after segmentation of retinal vasculature into superficial and deep capillary network and outer) OCTA images were graded into standardized categories. Agreement between the methods was evaluated statistically. RESULTS: In OCTA, a reduction of density of superficial capillaries, dilated vessels in the deep capillary network, anastomoses toward the superficial capillary network, and "new" vessels in the outer retina layers can be detected. The described anatomical features, especially in the deep capillary plexus and outer retina corresponded well with changes in FA. Classes of macular pigment distribution correlated most with classes of changes in OCTA superficial capillary plexus. CONCLUSION: Progressive changes in macular telangiectasia apparent in FA and macular pigment imaging are most obvious in the deep capillary network and outer retina in OCTA. Optical coherence tomography angiography offers a noninvasive technology to analyze vascular changes in the retina and choroid of patients with macular telangiectasia.

Macular telangiectasia--changes in macular pigment optical density during a 5-year follow-up.

PURPOSE: To quantitatively analyze the distribution of macular pigment (MP) over a period of 5 years and for monitoring progression of macular telangiectasia. METHODS: Macular pigment concentration (autofluorescence, excitation wavelengths: 488 and 514 nm) was determined at baseline and after 5 years in 43 eyes of 22 subjects (46-80 years; mean, 65.6 years; 10 men) participating in the macular telangiectasia project. RESULTS: Mean MP density at 0.5° declined in the segment (one eighth of a circle) with the highest MP optical density (-0.04 density units; P= 0.015), where density units (DU), and also averaged in the 2 segments that divided segments with detectable MP from those in which MP was no longer detectable (-0.04 density units; P = 0.0005). In the first segment mentioned, 2° values decreased to a lesser extent and not significantly. The diameter of MP loss expanded horizontally from 2.64 mm to 2.74 mm (P = 0.0001) but not vertically. Macular pigment density in the "halo" of peripheral MP at a mean of 5.44° (4.53-6.21°) increased (+0.01 DU; P= 0.01). CONCLUSION: Five years of follow-up resulted in central (0.5°) reduction and peripheral (4.53-6.21°) accumulation of MP. Longer period of follow-up may disclose significant changes in paracentral locations. The area of central MP loss expands in particular in a horizontal direction and less vertically. Centrifugal movement of MP during disease may explain our findings.

Long-term visual course after anti-VEGF therapy for exudative AMD in clinical practice evaluation of the German reinjection scheme.

BACKGROUND: In phase III trials, the therapeutic efficacy of anti-VEGF therapy with ranibizumab (Lucentis) in patients with choroidal neovascularization due to AMD was demonstrated in a 24-month period with monthly injections. Other studies and models suggested that flexible reinjection regimens can provide similar visual results. The aim of the present study was to evaluate the flexible, predominantly visual acuity-driven ranibizumab retreatment regimen in clinical practice in Germany. PATIENTS AND METHODS: Best-corrected visual acuity (VA, logMAR) and central retinal thickness (CRT) were recorded initially and every 4-6 weeks during follow-up (mean follow-up 75.5 weeks) from 152 eyes. All eyes were treated initially 3 times with ranibizumab at 4-weekly intervals, and retreated with another three injections if visual acuity decreased and/or CRT increased (>100 µm), and/or if new angiographic leakage and/or new retinal hemorrhages developed. Visual acuity development was analyzed in the whole group. A quartile analysis was also performed, and visual course was correlated with CRT. In all groups, numbers and times of reinjections within the first year were registered and analyzed. RESULTS: An increase in mean VA of 0.14 (SD 0.22) logMAR could be observed after 3 months, but during follow-up from months 3 to 12 the mean visual acuity decreased again by 0.14 (SD 0.24) logMAR, and was similar to the initial VA despite several reinjections (mean five injections). Stratification of patients according to the visual effect after 3 months (quartile analysis) demonstrated a differentiation of the visual course. Quartile 1, with the largest increase in VA after 3 months and reduction of the retinal edema, lost this positive effect during follow-up (100% of eyes received further injections). In contrast, quartile 2, with a minor increase, and quartile 3 demonstrated a stabilized response during follow-up (80% reinjections), while quartile 4 demonstrated a further loss in VA despite reinjections initially and during follow-up (60% reinjections). CONCLUSIONS: The flexible, predominantly visual acuity-driven ranibizumab retreatment regimen employed in clinical practice in Germany generally resulted in a loss of initially gained VA during 12 months of follow-up. Subgroup analysis showed that this negative effect was especially present in patients with relatively bad VA at treatment entry as well as the highest visual gain. Because this result demonstratse that a visual acuity-related retreatment regimen can not preserve the initial positive treatment effects with ranibizumab in exudative AMD, a revision of this schematic retreatment regimen used in Germany and adaptation to more sensitive retreatment parameters is recommended.

Idiopathic macular telangiectasia type 2: distribution of macular pigment and functional investigations.

PURPOSE: Analysis and categorization of macular pigment (MP) distribution in type 2 idiopathic macular telangiectasia (IMT2) with regard to a possible grading scale for the severity of the disease. METHODS: Nineteen IMT2 patients were examined including visual acuity (VA), fundus biomicroscopy, fluorescein angiography (FLA), microperimetry and optical coherence tomography (OCT). Distribution of MP was analyzed and categorized in MP density maps calculated from autofluorescence images obtained at 488 and 514 nm excitation wavelengths. RESULTS: Typical features in MP density maps are in class I (n=8), a triangular segment of reduced MP in the temporal fovea and central accumulation of MP, class II (n=12), further expansion of the segment and vanishing of central accumulation, and class III (n=18), oval effacement of MP centrally, surrounding halo of MP at 5-7 degrees eccentricity. These classes were associated with the stages of the disease and increasing restrictions in visual function. CONCLUSION: Association between changes in MP distribution, stages of IMT2 and restrictions in visual functions suggests that the classification of MP patterns reflects a severity scale for IMT2. Degenerative processes causing impairments in transport and storage of lutein (L) and zeaxanthin (Z) leading to secondary vascular changes may play a causative role in the disease.

Macular telangiectasia: patterns of distribution of macular pigment and response to supplementation.

PURPOSE: By analyzing the patterns of macular pigment (MP) in type 2 idiopathic telangiectasia eyes, different stages in the changes reflecting the extent of disease can be observed. The purpose of this study was to determine whether the amount and the pattern of MP can be influenced by supplementation. METHOD: Eleven patients with type 2 idiopathic telangiectasia received 12 mg lutein and 0.6 mg zeaxanthin (Ocuvite Lutein AMD) daily for 9 months. For a period of 12 months, MP concentration was determined every 3 months by autofluorescence (2 excitation wavelengths: 488 and 514 nm). RESULTS: When central accumulation of MP was similar to that in healthy subjects (with segment of reduced MP in the temporal fovea: MP Class I), supplementation enriched the MP at 0.5 degrees, 2 degrees, and 5 degrees to 6 degrees. In MP Class II (reduced concentration of MP centrally), accumulation could be detected at 2 degrees and 5 degrees to 6 degrees but not centrally. In MP Class III (oval-shaped effacement of MP centrally, surrounding oval-shaped ring of MP at 5 degrees-7 degrees eccentricity), supplementation promoted MP accumulation only at 5 degrees to 6 degrees. CONCLUSION: After oral supplementation with lutein/zeaxanthin, an increase in the MP was detected only in areas where the MP was present at baseline. Supplementation did not produce an increase in the area where the MP was absent. Degenerative processes causing an impairment in transport and storage of lutein and zeaxanthin may play a leading role in the pathogenesis of type 2 idiopathic telangiectasia.

Changes of macular pigment optical density in elderly eyes: a longitudinal analysis from the MARS study.

BACKGROUND: Macular pigment (MP) has been related to the occurrence of age related macular degeneration (AMD). We investigated prospectively in eyes of elderly individuals how magnitude and spatial distribution of MP had changed after 4 years. METHODS: The study included 380 eyes from 237 participants of the Münster Ageing and Retina Study cohort which were free of advanced stages of AMD. MP optical density (MPOD) was measured in density units (D.U.) at eccentricities of 0.25°, 0.5°, 1.0° and 2.0° from the fovea using dual-wavelength autofluorescence; ring-like MP distributions were identified from MP density profiles. Changes were assessed with mixed linear models. RESULTS: The study participants' mean age at baseline was 70.5 years. Early AMD was present in 150 study eyes (39.5 %) and a ring-like distribution of MPOD was found in 87 study eyes (22.9 %). After a median follow-up time of 3.96 years, the MPOD averaged over all eyes was slightly raised at the central fovea (from 0.658 to 0.670 D.U. (relative change +1.8 %), p = 0.08) and most markedly at 2.0° (from 0.157 to 0.172 D.U. (+9.5 %), p < 0.001). Multivariate analyses, adjusting for sex, body mass and carotenoid supplement intake, revealed that MPOD increments, at any distance from the fovea, were slightly less pronounced in older eyes. Serum concentrations of lutein at follow-up, presumably reflecting recent intake of antioxidant supplements, raised MPOD levels significantly at 1.0° and 2.0° (both p < 0.01) but not in the central fovea. Early AMD at baseline and ring-like MPOD distribution did not significantly impact on MPOD changes over time. A ring-like spatial distribution of MPOD persisted in over 80 % of the affected eyes. CONCLUSIONS: Overall, the magnitude and spatial arrangement of MPOD was remarkably stable over time in elderly eyes. Significant MPOD rises in perifoveal regions probably indicate effects of lutein containing supplements. The persistence of ring-like MPOD distributions over time seems to suggest their determination by anatomical structures.

Profiles of macular pigment optical density and their changes following supplemental lutein and zeaxanthin: new results from the LUNA study.

PURPOSE: Based on latest analyses disclosing an inverse association between ring-like structures in macular pigment (MP) spatial profile and age-related macular degeneration, we performed additional analyses of MP measurements obtained in participants of our earlier lutein nutrition effects measured by autoflourescence (LUNA) study to disclose if oral lutein (L) and zeaxanthin (Z) can attenuate, amplify, or generate a ring structure. METHODS: A total of 97 subjects attended the last follow-up visit 3 months after discontinuation of a 6-month trial of 12 mg L and 1 mg Z supplementation. Of the subjects, 11 eyes had a secondary peak (ring-like structure) and 8 had an implied pericentral plateau/shoulder on the slope of MP density profile (intermediate distribution). RESULTS: L and Z intake led to a general shift toward higher MP values in eyes without ring structure. The difference between mean optical density of retinal MP (Diff MPOD) at last follow-up and baseline was +0.16 density units (D.U.) at 0° eccentricity. Increments at 0.25°, 0.5°, 1°, and 2° (all P < 0.0001) decayed exponentially with higher eccentricity. MPOD showed comparatively slight central changes in eyes with ring and intermediate distribution (diff_MPOD at 0° +0.03 and +0.09), and increased at minimum (+0.06, P = 0.01) and maximum (+0.07, P = 0.02) of the ring, and at inner (+0.07, P = 0.04) and outer (+0.09, P = 0.01) radius of the pericentral "shoulder." CONCLUSIONS: Ring structures were neither attenuated nor generated de novo following supplementation. Individuals with second peak/implied plateau in the slope of the profile appear to have the most effective retinal stabilization of L and Z located at a pericentral rather than the central location.

Determinants of macular pigment optical density and its relation to age-related maculopathy: results from the Muenster Aging and Retina Study (MARS).

PURPOSE: The controversial protective effect of macular pigment (MP), consisting of lutein (L) and zeaxantin (Z), in age-related maculopathy (ARM) and its late-stage, age-related macular degeneration (AMD) is discussed. Determinants of MP optical density (MPOD) and its relation to ARM were investigated. METHODS: MPOD was accessed at eccentricities of 0.5° and 2.0° from the fovea in 369 participants in the 2.6-year follow-up examination of the prospective Muenster Aging and Retina Study using dual-wavelength analysis of autofluorescence images. ARM was graded from standardized fundus photographs according to the International Classification System. RESULTS: MPOD at 0.5° and 2.0° between pairs and within single eyes was strongly correlated (P < 0.001). Smoking and body mass index showed moderately inverse associations with MPOD at 2.0°, and age was positively related to MPOD at both eccentricities. Serum L, measured at the baseline examination, was significantly associated with MPOD measured at follow-up. Likewise, use of L/Z-containing supplements raised MPOD. Crude mean MPOD increased with ascending stage of ARM. However, adjustment for influential factors and exclusion of L supplement users removed differences of mean MPOD between ARM stages. Considering further the accompanying eye, study eyes with ARM had significantly higher MPOD when the contralateral eye had AMD. CONCLUSIONS: MPOD levels showed a high degree of intraindividual concordance and interindividual variability. Long-standing serum L levels, and in particular L supplementation, were the strongest determinants of MPOD. The hypothetical inverse association between MPOD and ARM stage was not confirmed.

The ringlike structure of macular pigment in age-related maculopathy: results from the Muenster Aging and Retina Study (MARS).

PURPOSE: The role of macular pigment (MP) in age-related maculopathy (ARM) is still not clearly understood. Recent studies have reported on variations in the spatial distribution of MP optical density (MPOD) including a secondary peak ("ring") in the slope of the MPOD profile. The authors investigated in a cross-sectional manner the presence of ringlike structures, their determinants, and their relationship with ARM. METHODS: In all, 369 participants of the Muenster Aging and Retina Study were examined using dual-wavelength analysis of autofluorescence images. ARM was graded using digital fundus photographs according to the International Classification System. RESULTS: A ringlike structure was observed in 73 (19.8%) study participants. The MP maximum of the ring was located on average at 0.85° and the minimum at 0.48° from the center of the fovea. Their concordance between pairs of eyes was highly significant. MPOD measured at eccentricities of 0°, 0.25°, and 0.5° from the fovea was significantly lower in eyes with ringlike structure, whereas it was significantly higher at 1.0° and 2.0° than that in eyes without the ring. Ringlike structures were significantly more common in females and never smokers and were found significantly less often in eyes with ARM than in healthy eyes, even after adjustment for influential factors (adjusted odds ratio, 0.347; 95% confidence interval, 0.196-0.617). CONCLUSIONS: Ringlike structures in the MP spatial profile are fairly common, show a high degree of bilaterality, and appeared inversely related with ARM.

Foveal RPE autofluorescence as a prognostic factor for anti-VEGF therapy in exudative AMD.

BACKGROUND: Autofluorescence (AF) of the retinal pigment epithelium (RPE) are thought to reflect metabolic activity of the RPE cells, which in turn is largely driven by photoreceptor outer segment renewal. In exudative AMD, choroidal new vessels (CNV) may be confined to Bruch's membrane, or transgress the RPE, with consequence loss of photoreceptor cells. It has been suggested that they may be distinguished with autofluorescence imaging. The aim of our study was to analyze the prognostic value of RPE autofluorescence in relationship to the therapeutic outcome of anti-VEGF (vascular endothelial growth factor) therapy in exudative AMD. PATIENTS AND METHODS: AF images (Heidelberg Retina Angiograph) were obtained from 95 eyes (95 patients, mean age 77.64 years, 39 male and 56 female) with exudative macular lesions and associated drusen before therapy with intravitreal Bevacizumab (Avastin). Increased, normal, or decreased AF of a central area with diameters of 500 and 1,000 microm around the foveola were distinguished, and compared with the outcome of central vision. As a measure of data reproducibility (inter- and intraobserver variability), the kappa statistics (K > 0.6 "good", K > 0.8 "excellent") and exact agreement in % were calculated. RESULTS: Analysis of AF showed a significant difference in outcome of visual acuity in eyes with changes in AF of the central 500 and 1000 microm (Mann-Whitney test, p500 mum < 0.001, p1,000 microm = 0.02). Comparison of eyes with increased AF to the other eyes also resulted a significant difference in visual acuity at follow-up (p (incr) < 0.001); those with decreased AF had no significant difference to the eyes with normal or increased AF (p (decr) = 0.1733). CONCLUSIONS: The RPE-AF of exudative AMD lesions varies greatly. The AF differences probably represent different kinds of metabolism disorders in the RPE. Furthermore, they apparently have a great influence on the chances of anti- vascular endothelial growth factor (VEGF) therapy success; in particular the development of visual acuity is less favorable in eyes with initially increased central AF.