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OPTICAL COHERENCE TOMOGRAPHY AND HISTOLOGY OF AGE-RELATED MACULAR DEGENERATION SUPPORT MITOCHONDRIA AS REFLECTIVITY SOURCES.

ABSTRACT: PURPOSE:Widespread adoption of optical coherence tomography has revolutionized the diagnosis and management of retinal disease. If the cellular and subcellular sources of reflectivity in optical coherence tomography can be identified, the value of this technology will be advanced even further toward precision medicine, mechanistic thinking, and molecular discovery. Four hyperreflective outer retinal bands are created by the exquisite arrangement of photoreceptors, Müller cells, retinal pigment epithelium, and Bruch membrane. Because of massed effects of these axially compartmentalized and transversely aligned cells, reflectivity can be localized to the subcellular level. This review focuses on the second of the four bands, called ellipsoid zone in a consensus clinical lexicon, with the central thesis that mitochondria in photoreceptor inner segments are a major independent reflectivity source in this band, because of Mie scattering and waveguiding. METHODS:We review the evolution of Band 2 nomenclature in published literature and discuss the origins of imaging signals from photoreceptor mitochondria that could make these organelles visible in vivo. RESULTS:Our recent data pertain to outer retinal tubulation, a unique neurodegenerative and gliotic structure with a highly reflective border, prominent in late age-related macular degeneration. High-resolution histology and multimodal imaging of outer retinal tubulation together provide evidence that inner segment mitochondria undergoing fission and translocation toward the nucleus provide the reflectivity signal. CONCLUSION:Our data support adoption of the ellipsoid zone nomenclature. Identifying subcellular signal sources will newly inform clinical.

SUBMITTER: Litts KM

PROVIDER: S-EPMC6230433 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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OPTICAL COHERENCE TOMOGRAPHY AND HISTOLOGY OF AGE-RELATED MACULAR DEGENERATION SUPPORT MITOCHONDRIA AS REFLECTIVITY SOURCES.

Litts Katie M KM Zhang Yuhua Y Freund K Bailey KB Curcio Christine A CA

Retina (Philadelphia, Pa.) 20180301 3

<h4>Purpose</h4>Widespread adoption of optical coherence tomography has revolutionized the diagnosis and management of retinal disease. If the cellular and subcellular sources of reflectivity in optical coherence tomography can be identified, the value of this technology will be advanced even further toward precision medicine, mechanistic thinking, and molecular discovery. Four hyperreflective outer retinal bands are created by the exquisite arrangement of photoreceptors, Müller cells, retinal p ...[more]

PMID: 29210936

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Project description:PurposeDescribe qualitative spectral-domain optical coherence tomography (SD-OCT) characteristics of eyes classified as intermediate age-related macular degeneration (nonadvanced AMD) from Age-Related Eye Disease Study 2 (AREDS2) color fundus photography (CFP) grading.DesignProspective cross-sectional study.ParticipantsWe included 345 AREDS2 participants from 4 study centers and 122 control participants who lack CFP features of intermediate AMD.MethodsBoth eyes were imaged with SD-OCT and CFP. The SD-OCT macular volume scans were graded for the presence of 5 retinal, 5 subretinal, and 4 drusen characteristics. In all, 314 AREDS2 participants with ?1 category-3 AMD eye and all controls each had 1 eye entered into SD-OCT analysis, with 63 eyes regraded to test reproducibility.Main outcome measuresWe assessed SD-OCT characteristics at baseline.ResultsIn 98% of AMD eyes, SD-OCT grading of all characteristics was successful, detecting drusen in 99.7%, retinal pigment epithelium (RPE) atrophy/absence in 22.9%, subfoveal geographic atrophy in 2.5%, and fluid in or under the retina in 25.5%. Twenty-eight percent of AMD eyes had characteristics of possible advanced AMD on SD-OCT. Two percent of control eyes had drusen on SD-OCT. Vision loss was not correlated with foveal drusen alone, but with foveal drusen that were associated with other foveal pathology and with overlying focal hyperreflectivity. Focal hyperreflectivity over drusen, drusen cores, and hyper- or hyporeflectivity of drusen were also associated with RPE atrophy.ConclusionsMacular pathologies in AMD can be qualitatively and reproducibly evaluated with SD-OCT, identifying pathologic features that are associated with vision loss, RPE atrophy, and even possibly the presence of advanced AMD not apparent on CFP. Qualitative and detailed SD-OCT analysis can contribute to the anatomic characterization of AMD in clinical studies of vision loss and disease progression.Financial disclosure(s)Proprietary or commercial disclosure may be found after the references.

Project description:PURPOSE:To detect and quantify choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography. DESIGN:Observational, cross-sectional study. PARTICIPANTS:A total of 5 normal subjects and 5 subjects with neovascular AMD were included. METHODS:A total of 5 eyes with neovascular AMD and 5 normal age-matched controls were scanned by a high-speed (100 000 A-scans/seconds) 1050-nm wavelength swept-source OCT. The macular angiography scan covered a 3 × 3-mm area and comprised 200 × 200 × 8 A-scans acquired in 3.5 seconds. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by 3-dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2-dimensional angiograms from the 3 layers. The CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views. MAIN OUTCOME MEASURES:The CNV angiogram, CNV area, and CNV flow index. RESULTS:En face OCT angiograms of CNV showed sizes and locations that were confirmed by fluorescein angiography (FA). Optical coherence tomography angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in 1 case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch's layer and classify type I and type II CNV. A feeder vessel could be identified in 1 case. Higher flow indexes were associated with larger CNV and type II CNV. CONCLUSIONS:Optical coherence tomography angiography provides depth-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD.

Project description:PurposeTo examine changes in retinal vasculature and ganglion cell layer (GCL) thickness in intermediate age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA).MethodsZeiss Cirrus Angioplex OCTA 6 × 6 mm scans and a macula 512 × 128 cube scans of the central retina were taken of 63 eyes with intermediate AMD and 51 control eyes. For OCTA scans, the superficial and deep capillary plexus were automatically segmented and vascular density quantified as total number of pixels contributing to the blood flow signal detectable by OCTA. Images were then skeletonized and vessel length, diameter index, morphology, and branching complexity determined. Foveal avascular zone (FAZ) characteristics and GCL thickness were extracted from in-built Angioplex software.ResultsVascular density was significantly reduced in the superficial capillary plexus of AMD eyes compared with normal eyes, particularly in the superior quadrant (42.4% ± 1.6% vs. 43.2% ± 1.4%; P < 0.05). A nonsignificant reduction was also seen in the deep capillary plexus (P = 0.06). Total vessel length and average vessel diameter were all significantly decreased in AMD eyes suggesting density changes were related to decreased vessel number and caliber. Vascular complexity and number of branch points was significantly decreased in the deep capillary plexus (P < 0.05) suggesting loss or significantly reduced flow of vessels. Average GCL thickness was also significantly reduced in the AMD eyes (P < 0.05). No significant changes in FAZ parameters were observed in AMD eyes.ConclusionsThis study suggests intermediate AMD affects both the quantity and morphology of inner retinal vasculature and may be associated with changes in inner retinal structure. This work builds upon the notion that AMD pathogenesis may extends beyond the outer retina.Translational relevanceBetter understanding of retinal vascular changes in AMD can provide insights in the development of treatment and prevention protocols for these diseases.

Project description:Importance:Whether optical coherence tomography angiography (OCT-A) outperforms OCT to detect glaucoma remains inconclusive. Objective:To compare (1) the diagnostic performance for detection of glaucoma and (2) the structure-function association between inner macular vessel density and inner macular thickness. Design, Setting, and Participants:This cross-sectional study included 115 patients with glaucoma and 35 healthy individuals for measurements of retinal thickness and retinal vessel density, segmented between the anterior boundary of internal limiting membrane and the posterior boundary of the inner plexiform layer, over the 3 × 3-mm2 macula using swept-source OCT. All participants were Chinese. Visual sensitivity corresponding to the 3 × 3-mm2 macular region was expressed in unlogged 1/lambert for investigation of the structure-function associations. Diagnostic performance was evaluated with area under the receiver operating characteristic curves (AUCs). The study was conducted between January 12, 2016, and December 12, 2016. Main Outcomes and Measures:Area under the receiver operating characteristic curve and R2 analysis. Results:Of the 115 patients with glaucoma, 42 (36.5%) were women (mean [SD] age, 53.5 [13.4] years); of the 35 individuals with healthy eyes, 25 (71.4%) were women (age, 60.6 [5.9] years). Inner macular vessel density and thickness were 4.3% (95% CI, 2.4%-6.1%) and 21.1 μm (95% CI, 17.4-24.9 μm) smaller, respectively, in eyes with glaucoma compared with healthy eyes. The AUC of mean inner macular thickness for glaucoma detection was greater than that of mean inner macular vessel density (difference, 0.17; 95% CI, 0.01-0.31; P = .03). At 90% specificity, the sensitivity of mean inner macular thicknesses for detection of glaucoma was greater than that of mean inner macular vessel densities (difference, 29.2%; 95% CI, 11.5%-64.6%; P = .02). The strength of the structure-function association was stronger for mean inner macular thickness than mean inner macular vessel density in the linear (difference in R2 = 0.38; 95% CI, 0.22-0.54; P < .001) and nonlinear (difference in R2 = 0.36; 95% CI, 0.21-0.51; P < .001) regression models. Conclusions and Relevance:In this study, OCT measurement of inner macular thickness shows a higher diagnostic performance to detect glaucoma and a stronger structure-function association than the currently used OCT-A measurement of inner macular vessel density. These findings may suggest that OCT-A of the macula has a limited role in the diagnostic evaluation of glaucoma.

Project description:BackgroundOCT-A is a recent imaging technique allowing a non-invasive assessment of the retinal and choroidal microvasculature, providing valuable data for the diagnosis and monitoring of wet AMD. We aim to determine the diagnosis accuracy, describe the morphological features, and assess the clinical activity of MNV in wet AMD using OCT-A.Materials and methodsWe conducted a descriptive cross-sectional study over a 15-month period. We enrolled patients with treatment-naive and treated MNV secondary to wet AMD. Macular OCT-A images were obtained using a swept-source OCT-A device (Triton SS-OCT, Topcon, Tokyo, Japan). Morphologic characteristics and semi-automated measurements were analyzed on the en face projection OCT-Angiograms. For the qualitative analysis, determined the sensitivity of detection of the MNV using OCTA. When detected, we described its shape, branching pattern, anastomoses and loops, and vessel termination. We looked for the halo sign and the feeder vessel. We then defined the lesion's "pattern" reflecting its exudative activity. For the quantitative analysis, we measured the lesion's area in square millimeters, when its borders were clearly defined.Results70 eyes from 55 patients were enrolled in this study. Type 1 MNV was identified in 57,1% eyes, type 2 in 21,4%, mixed type 1 and2 in 1,4%, type 3 in 1,4% and unclassified fibrotic MNV in 18,6%. 55,7% were active and 44,3% were inactive. Sensitivity of detection was 85% for type 1 lesions, 100% for type 2, mixed and type 3 lesions, and 92% for unclassified fibrotic lesions. It was 84,6% for active lesions and 96,8% for inactive lesions. For each detected lesion, shape was well-defined (medusa, glomerulus, seafan), long liner vessels or ill-defined. Branching pattern was dense or loose. Anastomoses and vascular loops were numerous or few. Termination was in an anastomotic arcade or in a dead-tree aspect. Halo sign was present or absent and feeder vessel was detected or not. All types combined, 41,3% of the lesions were "pattern I" and 58,7% were pattern II. We reported a correlation rate of 84,8% between the lesion's activity on MI and « pattern I » on OCT-A, and of 96,6% between absence of activity signs on MI and « pattern II » on OCT-A The mean area of inactive lesions was slightly larger than that of active lesions with respective values of 3.86 mm2 and 2.92 mm2.ConclusionOCT-A is a non-invasive, safe, and reproducible retinal imaging technique with a high sensitivity of detection of MNV in AMD. It provides useful qualitative and quantitative data. The involvement of OCT-A in the treatment decision for MNV in AMD is linked to identifying the "pattern" of the lesion reflecting its active or inactive status.

Dataset Information

OPTICAL COHERENCE TOMOGRAPHY AND HISTOLOGY OF AGE-RELATED MACULAR DEGENERATION SUPPORT MITOCHONDRIA AS REFLECTIVITY SOURCES.

Publications

OPTICAL COHERENCE TOMOGRAPHY AND HISTOLOGY OF AGE-RELATED MACULAR DEGENERATION SUPPORT MITOCHONDRIA AS REFLECTIVITY SOURCES.

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