Background
With FA and SD-OCT, different types of CNV in exudative AMD may be differentiated: type 1 CNV (within the sub-RPE space, typically corresponding to angiographically occult CNV), type 2 CNV ...(within the subretinal space, typically corresponding to angiographically classic CNV) and type 3 NV (intraretinal retinal angiomatous proliferation). OCT-angiography (OCT-A) is a new method to visualize vasculature based on flow characteristics. A correlation of type 1 and 2 CNV was performed.
Methods
Thirty-six eyes (17 type 1 CNV, 9 combined type 1 and 2 CNV, and 10 type 2 CNV) of 36 patients were examined by FA, SD-OCT and OCT-A. Standardized OCT-A segmentations were performed at the level of mid-choroid, choriocapillaris (CC), RPE and outer retina. On these images the size and demarcation of CNV lesions were classified: “not distinguishable”, “minor” or “sharp” demarcation. Furthermore, the size of the different CNV subtypes was determined and compared.
Results
Both types of CNV were visible in OCT-A. They could be detected on the slabs “mid-choroid”, “CC” and “RPE”. While type 1 CNV showed most often a minor demarcation from the surrounding vasculature, type 2 CNV showed nearly always a sharp demarcation. In addition, type 2 CNV extended into the slab “outer retina” and were much smaller than type 1 CNV.
Conclusions
Different types of CNV in exudative AMD can be visualized and differentiated with OCT-A. Type 1 CNV were larger with minor demarcation from the surrounding vasculature and were visible on the slab “mid-choroid”, “CC” and “RPE”. In contrast, type 2 CNV demonstrated a sharp demarcation from the surrounding vasculature reaching the slab “outer retina”.
Macular pigment (MP), consisting of lutein (L) and zeaxanthin (Z), is believed to protect the retina from photo-oxidative damage. The current study investigates, in terms of MP optical density (MPOD) ...and serum concentrations of its constituent carotenoids, response to supplemental L and Z, and co-antioxidants. An intervention (I) group, consisting of 108 subjects (mean ±SD age: 71.5 ±7.1 years), of which 92.6% exhibited features of age-related macular degeneration (AMD), received a daily supplement consisting of 12
mg L and 1
mg Z, both provided as ester 120
mg vitamin C, 17.6
mg vitamin E, 10
mg zinc, 40
μg selenium (Ocuvite Lutein™) for a period of 6 months. MPOD was measured, by 2-wavelength autofluorescence (AF), on five occasions during the period of supplementation, and once again 3 months following discontinuation of the supplement. A control (C) group of 28 subjects (mean ±SD age: 71.0 ±8.1 years), who received no dietary supplementation or modification, was examined at baseline and once again after a mean of 29.4 (±9.3) weeks. At baseline, mean (±SD) MPOD (at 0.5°) was 0.504 (±0.197) and 0.525 (±0.189) in the I and C groups, respectively. There was a statistically significant increase in MPOD (at 0.5°) for the I group (0.1 ±0.009;
p
<
0.0008), whereas no significant increase was seen in the C group (0.03 ±0.02;
p
>
0.05), over the period of supplementation. In order to classify supplemented subjects into quartiles, in terms of MPOD response, we calculated the difference between MPOD (at 0.5°) at visit 6 and at baseline (visit 1). Quartile 1 (the “non-responder” quartile) displayed no increase in MPOD (at 0.5°), in spite of rises seen in serum concentrations of L and Z. The three “responder” quartiles reached similar final plateaus of MPOD (at 0.5°), reflected in final mean (±SEM) values of 0.59 (±0.04) optical density unit (ODU), 0.64 (±0.03) ODU and 0.64 (±0.03) ODU for quartiles 2, 3 and 4, respectively. Subjects with low baseline MPOD were more likely to exhibit a dramatic rise in MPOD, or to exhibit no rise in MPOD, in response to supplements than subjects with medium to high baseline MPOD values. Supplementation with 12
mg L and 1
mg Z, combined with co-antioxidants, resulted in an increase of MPOD at 0.5° eccentricity in a majority of subjects, including those afflicted with AMD. However, there remains a substantial proportion of subjects for whom, in spite of rises in serum concentrations of L and Z in these subjects, MPOD augmentation in response to supplemental L, Z and co-antioxidants could not be detected over the study period, thus indicating that intestinal malabsorption of these carotenoids is not responsible for the lack of a macular response to such supplements. Further, our results suggest that saturable mechanisms play a role in the retinal capture and/or stabilisation of the macular carotenoids.
ObjectivesSelf-Examination Low-Cost Full-Field Optical Coherence Tomography (SELFF-OCT) is a novel OCT technology that was specifically designed for home monitoring of neovascular age-related macular ...degeneration (AMD). First clinical findings have been reported before. This trial investigates an improved prototype for patients with AMD and focusses on device operability and diagnostic accuracy compared with established spectral-domain OCT (SD-OCT).DesignProspective single-arm diagnostic accuracy study.SettingTertiary care centre (University Eye Clinic).Participants46 patients with age-related macular degeneration.InterventionsPatients received short training in device handling and then performed multiple self-scans with the SELFF-OCT according to a predefined protocol. Additionally, all eyes were examined with standard SD-OCT, performed by medical personnel. All images were graded by at least 2 masked investigators in a reading centre.Primary outcome measureRate of successful self-measurements.Secondary outcome measuresSensitivity and specificity of SELFF-OCT versus SD-OCT for different biomarkers and necessity for antivascular endothelial growth factor (anti-VEGF) treatment.ResultsIn 86% of all examined eyes, OCT self-acquisition resulted in interpretable retinal OCT volume scans. In these patients, the sensitivity for detection of anti-VEGF treatment necessity was 0.94 (95% CI 0.79 to 0.99) and specificity 0.95 (95% CI 0.82 to 0.99).ConclusionsSELFF-OCT was used successfully for retinal self-examination in most patients, and it could become a valuable tool for retinal home monitoring in the future. Improvements are in progress to reduce device size and to improve handling, image quality and success rates.Trial registration numberDRKS00013755, CIV-17-12-022384.
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.
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.
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).
Ringlike structures in the MP spatial profile are fairly common, show a high degree of bilaterality, and appeared inversely related with ARM.
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.
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.
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.
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.
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.
Purpose
Genetic factors contribute to the development and progression of age-related macular degeneration (AMD). We aimed to assess the association of drusen as phenotypic characteristics of early ...AMD and their progression with polymorphisms in the
CFH
,
ABCA1,
and
ARMS2
genes.
Methods
In the Münster Aging and Retina Study (MARS), drusen were detected in 406 patients with early AMD and 170 healthy controls according to the International Classification using fundus photographs, with a follow-up examination after 2.6 years (median). Six drusen features were assessed: drusen number (</≥20); confluence of drusen (</≥50 %), largest drusen size (</≥175 μm); area occupied by drusen (</≥10 %); most frequent drusen size (</≥175 μm), and presence of soft, indistinct drusen (no/yes). Based on these features, an unweighted summary drusen severity score (DSS; categorized in “low”, “intermediate” and “high”) was calculated. The relationship of each drusen feature and the DSS with
CFH
rs1061170,
ABCA1
rs1883025, and
ARMS2
rs10490924 at baseline and after 2.6 years was analyzed using multivariate logistic regression models.
Results
Cross-sectionally, each drusen feature was associated with a higher frequency of the
CFH
and
ARMS2
risk variants. Compared to healthy eyes, the
CFH
risk variant was more common in eyes with early as well as advanced drusen features, while the
ARMS2
variant was only associated with advanced drusen. After 2.6 years, 43 % of the eyes showed a progression of at least 1 unit in the DSS. The progression from low to higher DSS was inversely associated with
ABCA1
(OR = 0.54), and the progression from intermediate to high DSS was positively related to
CFH
rs1061170 (OR = 2.3;
p
< 0.05 for each).
Conclusions
Variants in
CFH
,
ABCA1
, and
ARMS2
genes are related to the presence and progression of drusen in early AMD.
CFH
and, inversely,
ABCA1
seem to be involved in early drusen development, while the role of
ARMS2
is more pronounced in advanced stages of early AMD.
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.
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.
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.
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.
Background: The clinical appearance of macular neovascularization (MNV) in age-related macular degeneration (nAMD) varies widely, but so far, this has had no relevance in terms of therapeutic ...approaches or prognosis. Therefore, our purpose was to investigate if and which differences exist in the vascular architecture of MNV and to quantify them. Methods: In 90 patients with newly diagnosed nAMD, MNV was identified by means of optical coherence tomography angiography (OCTA), and automated quantitative vascular analysis was carried out. The analyzed vascular parameters were area, flow, fractal dimension (FD), total vascular length (sumL), number of vascular nodes (numN), flow, and average vessel caliber (avgW). The current classification of MNVs divides them according to their localization into type 1 (grown from the choroid below the RPE), type 2 (grown from the choroid through RPE), and type 3 (grown from the retina toward the RPE). We compared the analyzed vascular parameters of each of the three MNV types. Kruskal−Wallis test was applied, Dunn test was performed for post hoc analysis, and for pairwise comparison, p-values were adjusted using Bonferroni comparison. Results: Regarding the MNV area, there was no significant difference between types 1 and 2, but type 3 was significantly smaller than types 1 and 2 (p < 0.00001). For FD, types 1 and 2 did not differ significantly, but again, type 3 was lower than type 1 and 2 (p < 0.00001). The numN were significantly higher in types 1 and 3 than in 2 (p < 0.005), but not between types 1 and 3. No significant differences were found between MNV types for flow. As for sumL, types 1 and 2 did not differ significantly, but type 3 was significantly lower than types 1 and 2 (p < 0.00001). For avgW, there was no significant difference between types 1 and 2 or between types 2 and 3, but type 3 was significantly larger than type 1 (p < 0.05). Conclusions OCTA yields detailed information on the vascular morphology of MNV in patients with nAMD and is able to show differences among types 1, 2, and 3. Especially comparing types 1 and 2 with type 3 reveals significant differences in area, FD, sumL, and numN. One explanation could be the similar pathogenesis of types 1 and 2 with their origin in the choroid and their growth towards the retinal pigment epithelium (RPE), whereas type 3 originates in the deep capillary plexus. Between types 1 and 2, however, only the numN differ significantly, which could be due to the fact that type 1 spreads horizontally below the RPE and, thus, display more vascular branching, while type 2 grows more vertically through the RPE and under the neurosensory retina. Detailed information about the pathologic vasculature is important for proper monitoring of the disease and to assess the efficacy of medication, especially with regard to new substances. This should be taken into consideration in future studies.
Purpose
The aim of this study was to find out whether the vascular architecture of untreated macular neovascularisations (MNV) in neovascular age-related macular degeneration (nAMD) as visualised ...with optic coherence tomography angiography (OCTA) is associated with functional and known morphological alterations of the retina in optic coherence tomography (SD-OCT).
Methods
The study design was retrospective with consecutive patient inclusion. In 107 patients with newly diagnosed nAMD, MNV were detected by means of OCTA and automated quantitative vascular analysis was performed. The MNV characteristics measured were area, flow density, total vascular length (sumL), density of vascular nodes (numN), fractal dimension (FD) and average vascular width (avgW). These parameters were assessed for associations with vision (BCVA), central retinal thickness (CRT), fluid distribution, the elevation of any pigment epithelial detachment (PED), the occurrence of subretinal haemorrhage and atrophy.
Results
BCVA was significantly worse with greater MNV area and sumL. Fluid distribution differed significantly in relation to area (
p
< 0.005), sumL (
p
< 0.005) and FD (
p
= 0.001). Greater PED height was significantly associated with higher numN (
p
< 0.05) and lower avgW (
p
< 0.05). Atrophy was present significantly more often in MNV with larger area (
p
< 0.05), higher sumL (
p
< 0.05) and higher flow density (
p
= 0.002). None of the MNV parameters had a significant association with CRT or the occurrence of haemorrhage.
Conclusion
OCTA is not restricted to evaluation of secondary changes but offers the opportunity to analyse the vascular structure of MNV in detail. Differences in vascular morphology are associated with certain secondary changes in retinal morphology. There are thus grounds for optimism that further research may identify and classify OCTA-based markers to permit more individualised treatment of nAMD.
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