Optical Coherence Tomography to Assess Neurodegeneration in Phenylalanine Hydroxylase Deficiency.
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ABSTRACT:
SUBMITTER: Lotz-Havla AS
PROVIDER: S-EPMC8703042 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Axonal and neuronal degeneration are important features of multiple sclerosis (MS) and other neurologic disorders that affect the anterior visual pathway. Optical coherence tomography (OCT) is a non-invasive technique that allows imaging of the retinal nerve fiber layer (RNFL), a structure which is principally composed of ganglion cell axons that form the optic nerves, chiasm, and optic tracts. Since retinal axons are nonmyelinated until they penetrate the lamina cribrosa, the RNFL is an ideal structure (no other central nervous system tract has this unique arrangement) for visualizing the processes of neurodegeneration, neuroprotection and, potentially, even neuro-repair. OCT is capable of providing high-resolution reconstructions of retinal anatomy in a rapid and reproducible fashion and permits objective analysis of the RNFL (axons) as well as ganglion cells and other neurons in the macula. In a systematic OCT examination of multiple sclerosis (MS) patients, RNFL thickness and macular volumes are reduced when compared to disease-free controls. Conspicuously, these changes, which signify disorganization of retinal structural architecture, occur over time even in the absence of a history of acute demyelinating optic neuritis. RNFL axonal loss in MS is most severe in those eyes with a corresponding reduction in low-contrast letter acuity (a sensitive vision test involving the perception of gray letters on a white background) and in those patients who exhibit the greatest magnitude of brain atrophy, as measured by validated magnetic resonance imaging techniques. These unique structure-function correlations make the anterior visual pathway an ideal model for investigating the effects of standard and novel therapies that target axonal and neuronal degeneration. We provide an overview of the physics of OCT, its unique properties as a non-invasive imaging technique, and its potential applications toward understanding mechanisms of brain tissue injury in MS, other optic neuropathies, and neurologic disorders.
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Project description:We propose an all-optical Fourier transformation system for real-time massive data processing in high speed optical coherence tomography (OCT). In the so-called optical computing OCT, fast Fourier transformation (FFT) of A-scan signal is optically processed in real time before being detected by photoelectric detector. Therefore, the processing time for interpolation and FFT in traditional Fourier domain OCT can be dramatically eliminated. A processing rate of 10 mega-A-scans/second was experimentally achieved, which is, to our knowledge, the highest speed for OCT imaging. Due to its fiber based all-optical configuration, this optical computing OCT system is ideal for ultrahigh speed volumetric OCT imaging in clinical application.
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Project description:Optical coherence tomography (OCT) is the gold standard for quantitative ophthalmic imaging. The majority of commercial and research systems require patients to fixate and be imaged in a seated upright position, which limits the ability to perform ophthalmic imaging in bedridden or pediatric patients. Handheld OCT devices overcome this limitation, but image quality often suffers due to a lack of real-time aiming and patient eye and photographer motion. We describe a handheld spectrally encoded coherence tomography and reflectometry (SECTR) system that enables simultaneous en face reflectance and cross-sectional OCT imaging. The handheld probe utilizes a custom double-pass scan lens for fully telecentric OCT scanning with a compact optomechanical design and a rapid-prototyped enclosure to reduce the overall system size and weight. We also introduce a variable velocity scan waveform that allows for simultaneous acquisition of densely sampled OCT angiography (OCTA) volumes and widefield reflectance images, which enables high-resolution vascular imaging with precision motion-tracking for volumetric motion correction and multivolumetric mosaicking. Finally, we demonstrate in vivo human retinal OCT and OCT angiography (OCTA) imaging using handheld SECTR on a healthy volunteer. Clinical translation of handheld SECTR will allow for high-speed, motion-corrected widefield OCT and OCTA imaging in bedridden and pediatric patients who may benefit ophthalmic disease diagnosis and monitoring.
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Project description:Background:Systemic lupus erythematosus (SLE) is a chronic, autoimmune and multisystemic disease. Recent studies with functional and structural magnetic resonance imaging and cognitive tests report an unexpectedly high frequency of central nervous system involvement, even in patients with asymptomatic SLE. The purpose of this study was to identify early signs of retinal neurodegeneration by comparing the thickness of the peripapillary retinal nerve fiber layer (pRNFL) and all macular layers between patients with SLE without ophthalmologic manifestations and healthy controls. The effect of disease duration and systemic comorbidities was also studied. Methods:Cross-sectional study, in which all participants underwent a complete ophthalmologic evaluation including retinal segmentation analysis with spectral domain-optical coherence tomography. Patients with SLE also received a detailed autoimmune disease specialist evaluation to assess the disease activity state and systemic involvement. For pRNFL thickness, the global and six peripapillary sectors were determined. Each macular layer thickness was determined in the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. A multiple linear regression analysis was performed to control for the effect of potential demographic, ophthalmic and systemic confounders. A second multivariable analysis, including patients with SLE only, was performed to assess the effect of disease-specific variables on the outcome measures. Results:Sixty-eight eyes of 68 patients with SLE and 50 eyes of 50 healthy controls were considered. The pRNFL was significantly thinner in the SLE group globally (p?=?0.026) and in the temporal superior (p?=?0.007) and temporal (p?=?0.037) sectors. In patients with SLE, chronic medication for hypercholesterolemia, hypertension and anticoagulants were associated with a significant thinning of the pRNFL. Patients with SLE presented significant thinning in the photoreceptor layer in five ETDRS areas (p?<?0.05). Shorter disease duration was associated with greater photoreceptor thinning in all ETDRS subfields. Neuropsychiatric SLE, higher disease activity and cardiovascular risk factors were associated with a thinner photoreceptor layer. No differences were observed in overall retinal thickness or the remaining macular layers. Conclusion:Patients with SLE present early signs of retinal neurodegeneration, as evidenced by a reduction in the photoreceptor layer and pRNFL. These signs are more pronounced in patients with higher cardiovascular risk burden or neuropsychiatric involvement.
| S-EPMC7171841 | biostudies-literature
Project description:This study aimed to identify the anterior segment high-resolution optical coherence tomography (HR-OCT) and HR-OCT angiography (HR-OCTA) features suggestive of limbal stem cell deficiency (LSCD) as confirmed by both impression cytology (IC) and in vivo confocal microscopy (IVCM). This was a single-centre prospective cross-sectional study including 24 eyes of 22 patients with clinical suspicion of LSCD based on peripheral superficial corneal vascularisation and scarring. On IC and IVCM, performed and interpreted by blinded observers, 12 eyes each were diagnosed with and without LSCD. Additionally, 10 eyes of 5 healthy volunteers with no ocular pathology were also imaged. The 136 HR-OCT/A images of these 34 eyes were analysed with respect to 12 imaging parameters; the parameters most suggestive of LSCD were identified and the sensitivity and specificity were calculated. In the LSCD group, the most common aetiology was ocular chemical burns (83%), whereas in the non-LSCD group, the most common aetiology was viral keratitis (67%). Multiple logistic regression analysis revealed that mean epithelial reflectivity, mean stromal reflectivity, and mean superficial vascular density were the parameters that were diagnostic of LSCD on HR-OCT/A (p < 0.0001). A ratio of the mean epithelial reflectivity to stromal reflectivity of >1.29 corresponded with a high sensitivity (91.7%) and specificity (98.75%); while a mean superficial vascular density score of >0.38 corresponded with a sensitivity of 97.9% and specificity of 73.8%. In conclusion, HR-OCT/A as a non-invasive imaging modality could prove to be a useful tool for confirming the diagnosis of LSCD, with potential clinical and research applications.
| S-EPMC8233779 | biostudies-literature
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.
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Project description:Acute glomerulonephritis caused by antiglomerular basement membrane marked by high mortality. The primary reason for this is delayed diagnosis via blood examination, urine analysis, tissue biopsy, or ultrasound and X-ray computed tomography imaging. Blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution, with reduced sensitivity. Optical coherence tomography is a noninvasive and high-resolution imaging technique that provides superior spatial resolution (micrometer scale) as compared to ultrasound and CT. Changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signals, such as optical attenuation and speckle variance. Furthermore, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, OCT has been utilized to quantify the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, its classification accuracy is clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improves from 76% to 95%. These results show that OCT combined with OCE can be a powerful tool for identifying and classifying nephritis. Therefore, the OCT/OCE method could potentially be used as a minimally invasive tool for longitudinal studies during the progression and therapy of glomerulonephritis as well as complement and, perhaps, substitute highly invasive tissue biopsies. Elastic-wave propagation in mouse healthy and nephritic kidneys.
| S-EPMC4956579 | biostudies-literature
Project description:The effectiveness of a phenylalanine-restricted diet to improve the outcome of individuals with phenylalanine hydroxylase deficiency (OMIM no. 261600) has been recognized since the first patients were treated 60 years ago. However, the treatment regime is complex, costly, and often difficult to maintain for the long term. Improvements and refinements in the diet for phenylalanine hydroxylase deficiency have been made over the years, and adjunctive therapies have proven to be successful for certain patients. Yet evidence-based guidelines for managing phenylalanine hydroxylase deficiency, optimizing outcomes, and addressing all available therapies are lacking. Thus, recommendations for nutrition management were developed using evidence from peer-reviewed publications, gray literature, and consensus surveys. The areas investigated included choice of appropriate medical foods, integration of adjunctive therapies, treatment during pregnancy, monitoring of nutritional and clinical markers, prevention of nutrient deficiencies, providing of access to care, and compliance strategies. This process has not only provided assessment and refinement of current nutrition management and monitoring recommendations but also charted a direction for future studies. This document serves as a companion to the concurrently published American College of Medical Genetics and Genomics guideline for the medical treatment of phenylalanine hydroxylase deficiency.
| S-EPMC3918542 | biostudies-literature
Project description:Spectral-domain optical coherence tomography (SD-OCT) represents a reliable tool for retinal layer volume and thickness measurement. The aim of this study was to evaluate retinal changes indicating neurodegenerative processes in patients with end-stage renal disease (ESRD) compared to healthy controls. This was a cross-sectional, single-center study comprising 32 ESRD patients and 38 controls. Sectoral retinal nerve fiber layer (RNFL) thickness and retinal layer volumes were obtained by SD-OCT. Age- and gender-adjusted retinal layer volumes such as total retinal volume (p?=?0.037), ganglion cell layer volume (GCL, p?=?0.003), ganglion cell layer - inner plexiform layer volume (GCL-IPL, p?=?0.005) and inner retinal layer volume (IRL, p?=?0.042) of the right eye were lower in ESRD patients. Inner plexiform layer volume of both eyes (IPL, right eye: p?=?0.017; left eye: 0.044) was reduced, as was RNFL thickness in the temporal superior sector (right eye: p?=?0.016). A subgroup analysis excluding patients with diabetes revealed that GCL (p?=?0.014) and GCL-IPL volume of the right eye (p?=?0.024) and temporal superior sector of the RNFL scan (p?=?0.021) in ESRD patients were still significantly thinner. We observed a decrease in several retinal layer volumes and temporal RNFL thickness indicative of retinal neurodegenerative processes in patients with ESRD.
| S-EPMC7093533 | biostudies-literature
Project description:ImportanceMild traumatic brain injury (TBI) may predispose individuals to progressive neurodegeneration.ObjectiveTo identify evidence of neurodegeneration through longitudinal evaluation of changes in retinal layer thickness using optical coherence tomography in veterans with a history of mild TBI.Design, setting, and participantsThis longitudinal cohort study evaluated veterans who were receiving services at the Minneapolis Veterans Affairs Health Care System. Symptomatic or mild TBI was diagnosed according to the Mayo TBI Severity Classification System. Participants in the age-matched control group had no history of TBI. Participants with any history or evidence of retinal or optic nerve disease that could affect retinal thickness were excluded. Data analysis was performed from July 2019 to February 2020.ExposuresThe presence and severity of mild TBI were determined through consensus review of self-report responses during the Minnesota Blast Exposure Screening Tool semistructured interview.Main outcomes and measuresChange over time of retinal nerve fiber layer (RNFL) thickness.ResultsA total of 139 veterans (117 men [84%]; mean [SD] age, 49.9 [11.1] years) were included in the study, 69 in the TBI group and 70 in the control group. Veterans with mild TBI showed significantly greater RNFL thinning compared with controls (mean [SE] RNFL slope, -1.47 [0.24] μm/y vs -0.31 [0.32] μm/y; F1,122 = 8.42; P = .004; Cohen d = 0.52). Functionally, veterans with mild TBI showed greater declines in visual field mean deviation (mean [SE] slope, -0.09 [0.14] dB/y vs 0.46 [0.23] dB/y; F1,122 = 4.08; P = .046; Cohen d = 0.36) and pattern standard deviation (mean [SE] slope, 0.09 [0.06] dB/y vs -0.10 [0.07] dB/y; F1,122 = 4.78; P = .03; Cohen d = 0.39) and high spatial frequency (12 cycles/degree) contrast sensitivity compared with controls. Cognitively, there was a significantly greater decrease in the number of errors over time during the Groton Maze Learning Test (GMLT) in controls compared with veterans with mild TBI (mean [SE] slope, -9.30 [1.48] errors/y vs -5.23 [1.24] errors/y; F1,127 = 4.43; P = .04; Cohen d = 0.37). RNFL tissue loss was significantly correlated with both worsening performance on the GMLT over time (Spearman ρ = -0.20; P = .03) and mild TBI severity (Spearman ρ = -0.25; P = .006). The more severe the mild TBI (larger Minnesota Blast Exposure Screening Tool severity score), the faster the reduction in RNFL thickness (ie, the more negative the slope) across time.Conclusions and relevanceThis cohort study found longitudinal evidence for significant, progressive neural degeneration over time in veterans with mild TBI, as indicated by greater RNFL tissue loss in patients with mild TBI vs controls, as well as measures of function. These results suggest that these longitudinal measures may be useful biomarkers of neurodegeneration. Changes in this biomarker may provide early detection of subsequent cognitive and functional deficits that may impact veterans' independence and need for care.
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