Age-related Macular Degeneration Images Research Articles

Unleashing the power of optical attenuation coefficients to facilitate segmentation strategies in OCT imaging of age-related macular degeneration: perspective.

The use of optical attenuation coefficients (OAC) in optical coherence tomography (OCT) imaging of the retina has improved the segmentation of anatomic layers compared with traditional intensity-based algorithms. Optical attenuation correction has improved our ability to measure the choroidal thickness and choroidal vascularity index using dense volume scans. Algorithms that combine conventional intensity-based segmentation with depth-resolved OAC OCT imaging have been used to detect elevations of the retinal pigment epithelium (RPE) due to drusen and basal laminar deposits, the location of hyperpigmentation within the retina and along the RPE, the identification of macular atrophy, the thickness of the outer retinal (photoreceptor) layer, and the presence of calcified drusen. OAC OCT algorithms can identify the risk-factors that predict disease progression in age-related macular degeneration.

Reticular Pseudodrusen: Interreader Agreement of Evaluation on OCT Imaging in Age-Related Macular Degeneration

PurposeTo determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence.DesignInterreader agreement study.ParticipantsTwelve readers from 6 reading centers.MethodsAll readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to ≥ 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image.Main Outcome MeasuresInterreader agreement, as assessed by Gwet’s first-order agreement coefficient (AC1).ResultsWhen evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions, and ≥ 5 definite lesions on en face IR images corresponding to Stage 2 or 3 lesions (AC1 = 0.60–0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions (AC1 = 0.58–0.65) and increasing levels of agreement with increasing RPD stage (AC1 = 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC1 = 0.68), but only fair agreement for this evaluation on selected B-scans (AC1 = 0.30).ConclusionsThere was generally substantial or near-substantial—but not near-perfect—agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading.Financial Disclosure(s)Proprietary or commercial disclosure may be found after the references. To determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence. Interreader agreement study. Twelve readers from 6 reading centers. All readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to ≥ 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image. Interreader agreement, as assessed by Gwet’s first-order agreement coefficient (AC1). When evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions, and ≥ 5 definite lesions on en face IR images corresponding to Stage 2 or 3 lesions (AC1 = 0.60–0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions (AC1 = 0.58–0.65) and increasing levels of agreement with increasing RPD stage (AC1 = 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC1 = 0.68), but only fair agreement for this evaluation on selected B-scans (AC1 = 0.30). There was generally substantial or near-substantial—but not near-perfect—agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading.

Retromode Imaging in Age-Related Macular Degeneration.

Background and Objectives: Retromode is a relatively new retinal-imaging technique that is based on the transillumination principle and is obtained with a scanning laser ophthalmoscope that uses light in the infrared spectrum. The laser light penetrates into the deep retinal layers and the choroid. Retromode images are captured with a laterally displaced aperture, and the detector captures only the scattered light. The result is a high-contrast pseudo-three-dimensional image. Age-related macular degeneration (AMD) is a disabling retinal disease. AMD is characterized in its early stage by small and intermediate drusen formation, while the signs of intermediate AMD are large drusen and/or pigmentary abnormalities. Late AMD has two forms, geographic atrophy, which is the advanced form of dry AMD, and wet AMD. Most of the lesions of AMD are located in the outer layers of the retina. This new imaging method can provide a glimpse of the deep retinal layers' topographic changes in a non-invasive, fast, and effective way that can match the other imaging tools available. Materials and Methods: The literature review was performed by searching the PubMed database using the following combination of keywords: retromode imaging and age-related macular degeneration. Relevant images similar to the ones in the literature were identified and used as models. Results: The purpose of this article is to highlight the utility of incorporating retromode imaging into the multimodal evaluation of the retina in patients with AMD and to gather and integrate these findings into a brief but comprehensive paper. Conclusions: Retromode imaging is a good screening, diagnosis, and monitoring tool for patients with AMD.

Impact of the Aging Lens and Posterior Capsular Opacification on Quantitative Autofluorescence Imaging in Age-Related Macular Degeneration.

PurposeThe purpose of this study was to investigate quantitative autofluorescence (qAF8) in patients with and without early or intermediate age-related macular degeneration (AMD); to determine the impact of the aged crystalline lens and posterior capsular opacification (PCO).MethodsIn phakic and pseudophakic eyes ≥60 years, AMD status was determined by the Beckman system. PCO presence and severity was extracted from clinical records. qAF8 was calculated using custom FIJI plugins. Differences in qAF8, stratified by lens status, PCO severity, and AMD status, were analyzed using generalized estimating equations.ResultsIn 210 eyes of 115 individuals (mean age = 75.7 ± 6.6 years), qAF8 was lower in intermediate AMD compared to early AMD (P = 0.05). qAF8 did not differ between phakic and pseudophakic eyes (P = 0.8909). In phakic (n = 83) and pseudophakic (n = 127) eyes considered separately, qAF8 did not differ by AMD status (P = 0.0936 and 0.3494, respectively). Qualitative review of qAF images in phakic eyes illustrated high variability. In pseudophakic eyes, qAF8 did not differ with PCO present versus absent (54.5% vs. 45.5%). Review of implanted intraocular lenses (IOLs) revealed that 43.9% were blue-filter IOLs.ConclusionsqAF8 was not associated with AMD status, up to intermediate AMD, considering only pseudophakic eyes to avoid noisy images in phakic eyes. In pseudophakic eyes, qAF8 was not affected by PCO. Because blue-filter IOLs may reduce levels of exciting light for qAF8, future studies investigating qAF in eyes with different IOL types are needed.Translational RelevanceTo reduce variability in observational studies and clinical trials requiring qAF8, pseudophakic participants without blue-filter IOLs or advanced PCO should be preferentially enrolled.

Imaging of Age-Related Macular Degeneration by Adaptive Optics Scanning Laser Ophthalmoscopy in Eyes With Aged Lenses or Intraocular Lenses.

PurposeTo assess the performance of adaptive optics scanning laser ophthalmoscopy (AOSLO) in a large sample of eyes with or without age-related macular degeneration (AMD) and with cataracts or intraocular lenses (IOLs).MethodsPatients with various degrees of AMD and age-similar normal subjects underwent fundus photography. Cataract severity and IOL clarity were assessed by fundus reflex photographs. In phakic eyes, lenticular opacity was graded as nuclear, cortical, or posterior subcapsular cataract. In eyes with IOLs, lens clarity was assessed by posterior capsule opacification (PCO). Quality of AOSLO images of the macular photoreceptor mosaic was classified as good, adequate or inadequate by human graders in a subjective assessment of cone visibility.ResultsA total of 159 eyes in 80 subjects (41 males, 39 females, aged 72.5 ± 11.5 years, 16 normals) were examined. Seventy-nine eyes had IOLs, and 80 eyes were phakic. AOSLO produced good images in 91 eyes (57%), adequate images in eight eyes (5%), and inadequate images in 27 eyes (17%). AOSLO did not acquire images in 33 eyes (21%), because of dense lenticular opacity, widespread PCO, or problems specific to individual subjects.ConclusionsAOSLO images considered at least Adequate or better for visualizing cone photoreceptors were acquired from 62% of study eyes.Translational RelevanceAOSLO can be used as an additional imaging modality to investigate the structure of cone photoreceptors in research on visual function in AMD and in clinical trials involving older patients.

Assessment of Novel Genome-Wide Significant Gene Loci and Lesion Growth in Geographic Atrophy Secondary to Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a common threat to vision loss in individuals older than 50 years. While neovascular complications in AMD are treatable, there is currently no therapy for geographic atrophy secondary to AMD. Geographic atrophy lesion progression over time shows considerable interindividual variability, but little is known about prognostic factors. To elucidate the contribution of common genetic variants to geographic atrophy lesion growth. This pooled analysis combined 4 independent studies: the Fundus Autofluorescence Imaging in Age-Related Macular Degeneration (FAM) study, the Directional Spread in Geographic Atrophy (DSGA) study, the Age-Related Eye Disease Study (AREDS), and the Geographic Atrophy Treatment Evaluation (GATE) study. Each provided data for geographic atrophy lesion growth in specific designs. Patients with geographic atrophy secondary to AMD were recruited to these studies. Genotypes were retrieved through the database of Genotypes and Phenotypes (for AREDS) or generated at the Cologne Center for Genomics (for FAM, DSGA, and GATE). The correlation between square root-transformed geographic atrophy growth rate and 7 596 219 genetic variants passing quality control was estimated using linear regression. The calculations were adjusted for known factors influencing geographic atrophy growth, such as the presence of bilateral geographic atrophy as well as the number of lesion spots and follow-up times. Slopes per allele, 95% CIs, and P values of genetic variants correlated with geographic atrophy lesion growth. A total of 935 patients (mean [SD] age, 74.7 [7.8] years; 547 female participants [59.0%]) were included. Two gene loci with conservative genome-wide significance were identified. Each minor allele of the genome-wide associated variants increased the geographic atrophy growth rate by a mean of about 15% or 0.05 mm per year. Gene prioritization within each locus suggests the protein arginine methyltransferase 6 gene (PRMT6; chromosome 1; slope, 0.046 [95% CI, 0.026-0.066]; P = 4.09 × 10-8) and the lanosterol synthase gene (LSS; chromosome 21; slope, 0.105 [95% CI, 0.068-0.143]; P = 4.07 × 10-7) as the most likely progression-associated genes. These data provide further insight into the genetic architecture of geographic atrophy lesion growth. Geographic atrophy is a clinical outcome with a high medical need for effective therapy. The genes PRMT6 and LSS are promising candidates for future studies aimed at understanding functional aspects of geographic atrophy progression and also for designing novel and targeted treatment options.

Optical coherence tomography-angiography in the multimodal imaging of age-related macular degeneration – a review

Макулната дегенерация, свързана с възрастта е водеща причина за необратима загуба на зрителната функция при хора над 65 години в развитите страни. Заболеваемостта ѝ се очаква да се увеличи с около 50% до 2020 г. предвид удължената продължителност на живот и увеличение на застаряващото население в световен мащаб. Загубата на централното зрение при късните форми на болестта - географска атрофия и хориоидална неоваскуларизация, представлява сериозен социален и икономически проблем. Това изисква редовен скрининг, ранно диагностициране и своевременно лечение на заболяването. Ангио-оптичната кохерентна томография e сравнително нов диагностичен метод. Базирайки се на своята неинвазивност, методът е все по-разпространен при макулната дегенерация, свързана с възрастта.

Optical Coherence Tomographic Angiography Imaging in Age-Related Macular Degeneration.

Optical coherence tomographic angiography (OCTA) is emerging as a rapid, noninvasive imaging modality that can provide detailed structural and flow information on retinal and choroidal vasculature. This review contains an introduction of OCTA and summarizes the studies to date on OCTA imaging in age-related macular degeneration.

Infrared reflectance imaging in age-related macular degeneration.

PurposeThe purpose of this article is to describe the appearance of age‐related macular degeneration (AMD) phenotypes using infrared (IR) reflectance imaging. IR reflectance imaging of the retina has the potential to highlight specific sub‐retinal features and pathology. However, its role in macular disease, specifically AMD, is often underestimated and requires clarification.Recent findingsRecent advances in clinical methods, imaging and scientific knowledge may be integrated to improve the accuracy of disease stratification in AMD. In particular, IR imaging holds an underutilised sensitivity to detect reticular pseudodrusen, which have been repeatedly described as a high‐risk sign for late AMD.SummaryThis article provides clinically relevant descriptions of AMD phenotypes using IR reflectance imaging. The findings are integrated with images from cases seen at the Centre for Eye Health. As primary eye‐care providers assume a critical role in the detection, diagnosis and management of AMD, we also provide a chair‐side reference to assist clinicians in interpreting IR images in AMD.

Directional Kinetics of Geographic Atrophy Progression in Age-Related Macular Degeneration with Foveal Sparing

To describe the directional kinetics of the spread of geographic atrophy (GA) spread in eyes with age-related macular degeneration and foveal sparing. Prospective, noninterventional natural history study: Fundus Autofluorescence Imaging in Age-Related Macular Degeneration (FAM; clinicaltrials.gov identifier, NCT00393692). Participants of the FAM study exhibiting foveal sparing of GA. Eyes were examined longitudinally with fundus autofluorescence (FAF; excitation wavelength, 488 nm; emission wavelength, >500 nm) and near infrared (NIR) reflectance imaging (Spectralis HRA+OCT or HRA2; Heidelberg Engineering, Heidelberg, Germany). Areas of foveal sparing and GA were measured by 2 independent readers using a semiautomated software tool that allows for combined NIR reflectance and FAF image grading (RegionFinder; Heidelberg Engineering). A linear mixed effect model was used to model GA kinetics over time. Change of GA lesion size over time (central vs. peripheral progression). A total of 47 eyes of 36 patients (mean age, 73.8±7.5 years) met the inclusion criteria. Mean follow-up time was 25.2±16.9 months (range, 5.9-74.6 months). Interreader agreement for measurements of GA and foveal-sparing size were 0.995 and 0.946, respectively. Mean area progression of GA toward the periphery was 2.27±0.22 mm(2)/year and 0.25±0.03 mm(2)/year toward the center. Analysis of square root-transformed data revealed a 2.8-fold faster atrophy progression toward the periphery than toward the fovea. Faster atrophy progression toward the fovea correlated with faster progression toward the periphery in presence of marked interindividual differences. The results demonstrate a significantly faster centrifugal than centripetal GA spread in eyes with GA and foveal sparing. Although the underlying pathomechanisms for differential GA progression remain unknown, local factors may be operative that protect the foveal retina-retinal pigment epithelial complex. Quantification of directional spread characteristics and modeling may be useful in the design of interventional clinical trials aiming to prolong foveal survival in eyes with GA.

Advances in Imaging in Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of severe visual loss in people aged 50 years or older in the developed world. Advances in ocular imaging have driven many of the major breakthroughs in our understanding of the disease’s pathogenesis, as well as many improvements in diagnosis and treatment. In this review, we describe the latest advances in ocular imaging applicable to patients with AMD. We begin with an overview of topographic imaging techniques, with an emphasis on emerging technologies such as ultrawidefield imaging, fundus autofluorescence, and adaptive optics. We next describe the latest advances in optical coherence tomography imaging, with an emphasis on novel image acquisition and analysis techniques of use for patients with AMD. In both cases, we describe the current state of the art for clinical imaging of patients with AMD and highlight new approaches likely to appear in clinical settings in the near future.

Spectral-domain Optical Coherence Tomography Imaging of Age-related Macular Degeneration

Spectral-domain optical coherence tomography (SD-OCT) high-speed, high-resolution imaging of the macula has become an essential tool for evaluating dry and wet age-related macular degeneration (AMD). This high-speed, high-resolution imaging strategy, combined with new innovative algorithms, permits reproducible measurements of the anatomic changes associated with AMD, which include drusen, geographic atrophy (GA), and choroidal neovascularization (CNV). To visualize drusen and larger retinal pigment epithelial detachments, an algorithm was developed for Cirrus HD-OCT (Carl Zeiss Meditec, Dublin CA) to detect elevations in the retinal pigment epithelium (RPE). To visualize GA, an algorithm was developed to provide en face visualization of the macula, which easily identifies and measures areas where the RPE has been lost. To visualize CNV and the associated macular fluid, an algorithm was developed to measure the retinal thickness between the internal limiting membrane and the RPE. No other imaging modality is capable of qualitatively and quantitatively following patients at all stages of AMD, which makes SD-OCT the ideal instrument for following disease progression and the effect of therapies.

Spectral-domain Optical Coherence Tomography Imaging of Age-related Macular Degeneration

Spectral-domain optical coherence tomography (SD-OCT) high-speed, high-resolution imaging of the macula has become an essential tool for evaluating dry and wet age-related macular degeneration (AMD). This high-speed, high-resolution imaging strategy, combined with new innovative algorithms, permits reproducible measurements of the anatomical changes associated with AMD, which include drusen, geographic atrophy (GA) and choroidal neovascularisation (CNV). To visualise drusen and larger retinal pigment epithelial detachments, an algorithm was developed for Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) to detect elevations in the retinal pigment epithelium (RPE). To visualise GA, an algorithm was developed to provide en face visualisation of the macula, which easily identifies and measures areas where the RPE has been lost. To visualise CNV and the associated macular fluid, an algorithm was developed to measure the retinal thickness between the internal limiting membrane and the RPE. No other imaging modality is capable of qualitatively and quantitatively following patients at all stages of AMD, which makes SD-OCT the ideal instrument for following disease progression and the effect of therapies.

Three-dimensional ultrahigh resolution optical coherence tomography imaging of age-related macular degeneration

Ultrahigh resolution optical coherence tomography (OCT) enhances the ability to visualize different intra retinal layers. In age-related macular degeneration (AMD), pathological changes in individual retinal layers, including photoreceptor inner and outer segments and retinal pigment epithelium, can be detected. OCT using spectral / Fourier domain detection enables high speed, volumetric imaging of the macula, which provides comprehensive three-dimensional tomographic and morphologic information. We present a case series of AMD patients, from mild drusen to more advanced geographic atrophy and exudative AMD. Patients were imaged with a research prototype, ultrahigh resolution spectral / Fourier domain OCT instrument with 3.5 microm axial image resolution operating at 25,000 axial scans per second. These cases provide representative volumetric datasets of well-documented AMD pathologies which could be used for the development of visualization and imaging processing methods and algorithms.

Autofluorescence Imaging in Age-Related Macular Degeneration Complicated by Choroidal Neovascularization: A Prospective Study

Autofluorescence Imaging in Age-Related Macular Degeneration Complicated by Choroidal Neovascularization: A Prospective Study

Autofluorescence Imaging in Age-Related Macular Degeneration Complicated by Choroidal Neovascularization: A Prospective Study

To determine if integrity of the retinal pigment epithelium (RPE)/photoreceptor complex as assessed by autofluorescence imaging can be predicted on the basis of visual acuity (VA), size, or fluorescein angiographic characteristics of the lesion in the early stage of choroidal neovascularization in age-related macular degeneration (AMD). Prospective, observational, consecutive case series. Seventy-nine eyes of 78 patients with untreated early-stage subfoveal neovascular AMD. Digital color fundus photography and fluorescein angiography were carried out by certified photographers using the same camera throughout the study. Confocal scanning laser ophthalmoscopy images were obtained using a retinal angiograph. Autofluorescence images were compared with digital fluorescein angiography and fundus color photographs using IMAGEnet. Autofluorescence at the macula was correlated with VA, angiographic lesion characteristics, lesion size, and length of symptoms. Of the 79 eyes studied, 40 had classic and predominantly classic choroidal neovascularization, 10 had minimally classic, 29 had occult, 75 were subfoveal, and 4 were juxtafoveal. In 54 eyes, autofluorescence was continuous at the central macula, and this correlated significantly with VA, lesion size, and symptom length but not choroidal neovascularization type. However, there was considerable overlap between the 2 groups such that the integrity of RPE autofluorescence could not be predicted on the basis of these criteria. Intact autofluorescence at the macula in early choroidal neovascularization correlates with VA, lesion size, and symptom length but not lesion type. None predict with any certainty the integrity of the outer retina. Our data suggest that the RPE/photoreceptor complex may be intact at the macula for several months in the presence of choroidal neovascularization, suggesting that VA might be rescued if treatment were effective in suppressing neovascular growth without damaging the RPE/retina complex, although this remains to be tested. It would be sensible to assess autofluorescence in treatment protocols to test this concept because it may be a marker for earlier disease and predict outcomes of treatment.

En pratique, apport et place respective des différentes explorations

Imaging of age-related macular degeneration mainly depends on the stage of the disease. Age-related maculopathy and geographic atrophy only require color or monochromatic fundus photographies. Exudative age-related macular degeneration requires first fluorescein angiography. The results of fluorescein angiography may lead to further investigations: indocyanine green angiography and/or optical coherence tomography. The latter is more and more frequently performed to monitor the follow up of treated choroidal neovascularization. La documentation de la dégénérescence maculaire liée à l’âge dépend essentiellement de la forme présentée. Les formes non exsudatives ne nécessitent, en règle générale, qu’une documentation par rétinographies en couleur ou en lumière monochromatique. Les formes exsudatives nécessitent, en première intention, une angiographie à la fluorescéine, éventuellement complétée par une angiographie au vert d’indocyanine (ICG) et/ou une tomographie par cohérence optique (OCT). Ce dernier examen prend une place de plus en plus importante pour la documentation du suivi thérapeutique des formes néovasculaires traitées.

Analysis of changes of color Doppler flow imaging in age-related macular degeneration

To study the specific imaging of age-related macular degeneration (AMD) by color Doppler flow imaging (CDFI). Routine CDFI was carried out in 98 cases of AMD to observe the character of blood flow in AMD, to establish the diagnosis criteria of different types of AMD and to different the AMD from malignant choroidal melanoma, metastatic carcinoma of the choroid, choroidal nevus and macular edema. CDFI in dry form AMD did not detect changes in most patients, mildly elevated lesions presented in some cases. In wet form of AMD, CDFI showed solid lesion with irregular surface contour. The internal structure of these lesions was middle degree. Choroidal excavation was not found. Numerous blood flow signals could be found at the base of the lesion. Spot blood flow signals were present on the surface of the lesion. There was no abnormal blood flow signal in the mass. The different acoustic properties between wet form and dry form included configuration, surface and internal structure, with or without vitreous hemorrhage. CDFI is a simple and reliable method in the diagnosis of AMD.

Three dimensional imaging in age-related macular degeneration

The ability of confocal scanning laser tomography to quantify the subretinal features was investigated. The slope ratios (anterior slope/posterior slope) of the axial intensity profiles were analyzed. The data fromnormal subjects showed only minimal influence of individual ocular pigmentation. In the eyes with agerelated macular degeneration, the light-tissue interactions vary according to the type of retinal features. Three-dimensional information could be obtained from the axial intensity profiles.