Effect of Disease Severity and Optic Disc Size on Diagnostic Accuracy of RTVue Spectral Domain Optical Coherence Tomograph in Glaucoma

PURPOSE. To evaluate the effect of disease severity and optic disc size on the diagnostic accuracies of optic nerve head (ONH), retinal nerve fiber layer (RNFL), and macular parameters with RTVue (Optovue, Fremont, CA) spectral domain optical coherence tomography (SDOCT) in glaucoma. METHODS. 110 eyes of 62 normal subjects and 193 eyes of 136 glaucoma patients from the Diagnostic Innovations in Glaucoma Study underwent ONH, RNFL, and macular imaging with RTVue. Severity of glaucoma was based on visual field index (VFI) values from standard automated perimetry. Optic disc size was based on disc area measurement using the Heidelberg Retina Tomograph II (Heidelberg Engineering, Dossenheim, Germany). Influence of disease severity and disc size on the diagnostic accuracy of RTVue was evaluated by receiver operating characteristic (ROC) and logistic regression models. RESULTS. Areas under ROC curve (AUC) of all scanning areas increased (P < 0.05) as disease severity increased. For a VFI value of 99%, indicating early damage, AUCs for rim area, average RNLI thickness, and ganglion cell complex-root mean square were 0.693, 0.799, and 0.779, respectively. For a VFI of 70%, indicating severe damage, corresponding AUCs were 0.828, 0.985, and 0.992, respectively. Optic disc size did not influence the AUCs of any of the SDOCT scanning protocols of RTVue (P > 0.05). Sensitivity of the rim area increased and specificity decreased in large optic discs. CONCLUSIONS. Diagnostic accuracies of RTVue scanning protocols for glaucoma were significantly influenced by disease severity. Sensitivity of the rim area increased in large optic discs at the expense of specificity. (Invest Ophthalmol Vis Sci. 2011;92:1290-1296) DOI:10.1167/iovs.10-5516

Effect of External Noise Correlation in Optical Coherence Resonance

Coherence resonance occurring in semiconductor lasers with optical feedback is studied via the Lang-Kobayashi model with external nonwhite noise in the pumping current. The temporal correlation and the amplitude of the noise have a highly relevant influence in the system, leading to an optimal coherent response for suitable values of both the noise amplitude and correlation time. This phenomenon is quantitatively characterized by means of several statistical measures.

Structure-function Relationships Using the Cirrus Spectral Domain Optical Coherence Tomograph and Standard Automated Perimetry

Purpose: To evaluate the relationship between glaucomatous structural damage assessed by the Cirrus Spectral Domain OCT (SDOCT) and functional loss as measured by standard automated perimetry (SAP). Methods: Four hundred twenty-two eyes (78 healthy, 210 suspects, 134 glaucomatous) of 250 patients were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study and from the African Descent and Glaucoma Evaluation Study. All eyes underwent testing with the Cirrus SDOCT and SAP within a 6-month period. The relationship between parapapillary retinal nerve fiber layer thickness (RNFL) sectors and corresponding topographic SAP locations was evaluated using locally weighted scatterplot smoothing and regression analysis. SAP sensitivity values were evaluated using both linear as well as logarithmic scales. We also tested the fit of a model (Hood) for structure-function relationship in glaucoma. Results: Structure was significantly related to function for all but the nasal thickness sector. The relationship was strongest for superotemporal RNFL thickness and inferonasal sensitivity (R(2) = 0.314, P < 0.001). The Hood model fitted the data relatively well with 88% of the eyes inside the 95% confidence interval predicted by the model. Conclusions: RNFL thinning measured by the Cirrus SDOCT was associated with correspondent visual field loss in glaucoma.

Coronary optical frequency domain imaging (OFDI) for in vivo evaluation of stent healing: comparison with light and electron microscopy

Coronary late stent thrombosis, a rare but devastating complication, remains an important concern in particular with the increasing use of drug-eluting stents. Notably, pathological studies have indicated that the proportion of uncovered coronary stent struts represents the best morphometric predictor of late stent thrombosis. Intracoronary optical frequency domain imaging (OFDI), a novel second-generation optical coherence tomography (OCT)-derived imaging method, may allow rapid imaging for the detection of coronary stent strut coverage with a markedly higher precision when compared with intravascular ultrasound, due to a microscopic resolution (axial approximately 10-20 microm), and at a substantially increased speed of image acquisition when compared with first-generation time-domain OCT. However, a histological validation of coronary OFDI for the evaluation of stent strut coverage in vivo is urgently needed. Hence, the present study was designed to evaluate the capacity of coronary OFDI by electron (SEM) and light microscopy (LM) analysis to detect and evaluate stent strut coverage in a porcine model.

Optical projection tomography reveals dynamics of HEV growth after immunization with protein plus CFA and features shared with HEVs in acute autoinflammatory lymphadenopathy

The vascular-stromal compartment of lymph nodes is important for lymph node function, and high endothelial venules (HEVs) play a critical role in controlling the entry of recirculating lymphocytes. In autoimmune and autoinflammatory diseases, lymph node swelling is often accompanied by apparent HEV expansion and, potentially, targeting HEV expansion could be used therapeutically to limit autoimmunity. In previous studies using mostly flow cytometry analysis, we defined three differentially regulated phases of lymph node vascular-stromal growth: initiation, expansion, and the re-establishment of vascular quiescence and stabilization. In this study, we use optical projection tomography to better understand the morphologic aspects of HEV growth upon immunization with ovalbumin/CFA (OVA/CFA). We find HEV elongation as well as modest arborization during the initiation phase, increased arborization during the expansion phase, and, finally, vessel narrowing during the re-establishment of vascular quiescence and stabilization. We also examine acutely enlarged autoinflammatory lymph nodes induced by regulatory T cell depletion and show that HEVs are expanded and morphologically similar to the expanded HEVs in OVA/CFA-stimulated lymph nodes. These results reinforce the idea of differentially regulated, distinct phases of vascular-stromal growth after immunization and suggest that insights gained from studying immunization-induced lymph node vascular growth may help to understand how the lymph node vascular-stromal compartment could be therapeutically targeted in autoimmune and autoinflammatory diseases.

Differential optical densities of intraretinal spaces

PURPOSE: To test the hypothesis that hyporeflective spaces in the neuroretina found on optical coherence tomography (OCT) examination have different optical reflectivities according to whether they are associated with exudation or degeneration. METHODS: Retrospective analysis of eyes with idiopathic perifoveal telangiectasia (IPT), diabetic macular edema (DME), idiopathic central serous chorioretinopathy (CSC), retinitis pigmentosa (RP), or cone dystrophy (CD) and eyes of healthy control subjects. OCT scans were performed. Raw scan data were exported and used to calculate light reflectivity profiles. Reflectivity data were acquired by projecting three rectangular boxes, each 50 pixels long and 5 pixels wide, into the intraretinal cystoid spaces, centrally onto unaffected peripheral RPE, and onto the prefoveolar vitreous. Light reflectivity in the retinal pigment epithelium (RPE), vitreous, and intraretinal spaces for the different retinal conditions and control subjects were compared. RESULTS: Reflectivities of the vitreous and the RPE were similar among the groups. Hyporeflective spaces in eyes with exudation (DME, RP, and CSC) had higher reflectivity compared with the mean reflectivity of the vitreous, whereas the cystoid spaces in the maculae of the eyes without exudation (CD and IPT) had a lower reflectivity than did the normal vitreous. CONCLUSIONS: Analysis of the light reflectivity profiles may be a tool to determine whether the density of hyporeflective spaces in the macula is greater or less than that of the vitreous, and may be a way to differentiate degenerative from exudative macular disease.

OPTiSPIM: integrating optical projection tomography in light sheet microscopy extends specimen characterization to nonfluorescent contrasts.

Mesoscopic 3D imaging has become a widely used optical imaging technique to visualize intact biological specimens. Selective plane illumination microscopy (SPIM) visualizes samples up to a centimeter in size with micrometer resolution by 3D data stitching but is limited to fluorescent contrast. Optical projection tomography (OPT) works with fluorescent and nonfluorescent contrasts, but its resolution is limited in large samples. We present a hybrid setup (OPTiSPIM) combining the advantages of each technique. The combination of fluorescent and nonfluorescent high-resolution 3D data into integrated datasets enables a more extensive representation of mesoscopic biological samples. The modular concept of the OPTiSPIM facilitates incorporation of the transmission OPT modality into already established light sheet based imaging setups.

Transversal and longitudinal images from the retina of the living eye using low coherence interferometry

An optical coherence tomography (OCT) system to produce both longitudinal and transversal images of the in vivo human eye is presented. For the first time, OCT transversal images collected from the living eye at 50-µm depth steps show details unobtainable with the state-of-the-art scanning laser ophthalmoscope. Images of up to 3×3?mm are produced from the retina in less than a second. For images larger than 1.6×1.6?mm, a path modulation is introduced by the galvanometric scanning mirror and is used as an effective phase modulation method.

Optical and structural ocular changes during incipient presbyopia

The primary aim of this thesis was to investigate the in vivo ocular morphological and contractile changes occurring within the accommodative apparatus prior to the onset of presbyopia, with particular reference to ciliary muscle changes with age and the origin of a myopic shift in refraction during incipient presbyopia. Commissioned semi-automated software proved capable of extracting accurate and repeatable measurements from crystalline lens and ciliary muscle Anterior Segment Optical Coherence Tomography (AS-OCT) images and reduced the subjectivity of AS-OCT image analysis. AS-OCT was utilised to document longitudinal changes in ciliary muscle morphology within an incipient presbyopic population (n=51). A significant antero-inwards shift of ciliary muscle mass was observed after 2.5 years. Furthermore, in a subgroup study (n=20), an accommodative antero-inwards movement of ciliary muscle mass was evident. After 2.5 years, the centripetal response of the ciliary muscle significantly attenuated during accommodation, whereas the antero-posterior mobility of the ciliary muscle remained invariant. Additionally, longitudinal measurement of ocular biometry revealed a significant increase in crystalline lens thickness and a corresponding decrease in anterior chamber depth after 2.5 years (n=51). Lenticular changes appear to be determinant of changes in refraction during incipient presbyopia. During accommodation, a significant increase in crystalline lens thickness and axial length was observed, whereas anterior chamber depth decreased (n=20). The change in ocular biometry per dioptre of accommodation exerted remained invariant after 2.5 years. Cross-sectional ocular biometric data were collected to quantify accommodative axial length changes from early adulthood to advanced presbyopia (n=72). Accommodative axial length elongation significantly attenuated during presbyopia, which was consistent with a significant increase in ocular rigidity during presbyopia. The studies presented in this thesis support the Helmholtz theory of accommodation and despite the reduction in centripetal ciliary muscle contractile response with age, primarily implicate lenticular changes in the development of presbyopia.

Transversal and longitudinal images from the retina of the living eye using low coherence interferometry

An optical coherence tomography (OCT) system to produce both longitudinal and transversal images of the in vivo human eye is presented. For the first time, OCT transversal images collected from the living eye at 50-µm depth steps show details unobtainable with the state-of-the-art scanning laser ophthalmoscope. Images of up to 3×3?mm are produced from the retina in less than a second. For images larger than 1.6×1.6?mm, a path modulation is introduced by the galvanometric scanning mirror and is used as an effective phase modulation method.

Measurement of scleral thickness in humans using anterior segment optical coherent tomography

Anterior segment optical coherent tomography (AS-OCT, Visante; Zeiss) is used to examine meridional variation in anterior scleral thickness (AST) and its association with refractive error, ethnicity and gender. Scleral cross-sections of 74 individuals (28 males; 46 females; aged between 18-40 years (27.7±5.3)) were sampled twice in random order in 8 meridians: [superior (S), inferior (I), nasal (N), temporal (T), superior-temporal (ST), superior-nasal (SN), inferior-temporal (IT) and inferior-nasal (IN)]. AST was measured in 1mm anterior-toposterior increments (designated the A-P distance) from the scleral spur (SS) over a 6mm distance. Axial length and refractive error were measured with a Zeiss IOLMaster biometer and an open-view binocular Shin-Nippon autorefractor. Intra- And inter-observer variability of AST was assessed for each of the 8 meridians. Mixed repeated measures ANOVAs tested meridional and A-P distance differences in AST with refractive error, gender and ethnicity. Only right eye data were analysed. AST (mean±SD) across all meridians and A-P distances was 725±46μm. Meridian SN was the thinnest (662±57μm) and I the thickest (806 ±60μm). Significant differences were found between all meridians (p<0.001), except S:ST, IT:IN, IT:N and IN:N. Significant differences between A-P distances were found except between SS and 6 mm and between 2 and 4mm. AST measurements at 1mm (682±48 μm) were the thinnest and at 6mm (818±49 μm) the thickest (p<0.001); a significant interaction occurred between meridians and A-P distances (p<0.001). AST was significantly greater (p<0.001) in male subjects but no significant differences were found between refractive error or ethnicity. Significant variations in AST occur with regard to meridian and distance from the SS and may have utility in selecting optimum sites for pharmaceutical or surgical intervention.

Optical micro-tomography “OPenT” allows the study of large toadfish Halobatrachus didactylus embryos and larvae

Batrachoidids, which include midshipman and toadfish are less known among embryologists, but are common in other fields. They are characteristic for their acoustic communication, and develop hearing and sound production while young juveniles. They lay large benthic eggs (>5mm) with a thick chorion and adhesive disk and slow development, which are particularly challenging for studying embryology. Here we took advantage of a classical tissue clearing technique and the OPenT open-source platform for optical tomography imaging, to image a series of embryos and larvae from 3 to 30mm in length, which allowed detailed 3D anatomical reconstructions non-destructively. We documented some of the developmental stages (early and late in development) and the anatomy of the delicate stato-acoustic organs, swimming bladder and associated sonic muscles. Compared to other techniques accessible to developmental biology labs, OPenT provided advantages in terms of image quality, cost of operation and data throughput, allowing identification and quantitative morphometrics of organs in larvae, earlier and with higher accuracy than is possible with other imaging techniques.

AUTOMATIC CORONARY WALL SEGMENTATION IN INTRAVASCULAR ULTRASOUND IMAGES USING BINARY MORPHOLOGICAL RECONSTRUCTION

Intravascular ultrasound (IVUS) image segmentation can provide more detailed vessel and plaque information, resulting in better diagnostics, evaluation and therapy planning. A novel automatic segmentation proposal is described herein; the method relies on a binary morphological object reconstruction to segment the coronary wall in IVUS images. First, a preprocessing followed by a feature extraction block are performed, allowing for the desired information to be extracted. Afterward, binary versions of the desired objects are reconstructed, and their contours are extracted to segment the image. The effectiveness is demonstrated by segmenting 1300 images, in which the outcomes had a strong correlation to their corresponding gold standard. Moreover, the results were also corroborated statistically by having as high as 92.72% and 91.9% of true positive area fraction for the lumen and media adventitia border, respectively. In addition, this approach can be adapted easily and applied to other related modalities, such as intravascular optical coherence tomography and intravascular magnetic resonance imaging. (E-mail: matheuscardosomg@hotmail.com) (C) 2011 World Federation for Ultrasound in Medicine & Biology.

Combined Laser and Intravitreal Triamcinolone for Proliferative Diabetic Retinopathy and Macular Edema: One-year Results of a Randomized Clinical Trial

PURPOSE: To evaluate laser combined with intravitreal triamcinolone acetonide (IVTA) for the management of patients with proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME). DESIGN: Randomized clinical trial. METHODS: SETTINGS: Single center. STUDY POPULATION: Twenty-two patients with bilateral treatment,naive moderate PDR and CSME. INTERVENTION: Laser (panretinal and macular) photocoagulation was performed in each eye, followed by IVTA in one randomly assigned eye. Best,corrected visual acuity (BCVA), fundus photography, and optical coherence tomography were performed at baseline and at months 1, 3, 6, 9, and 12. MAIN OUTCOME MEASURES:. Changes in BCVA, central macular thickness (CMT), and total macular volume (TMV). RESULTS: The mean logarithm of the minimal angle of resolution (logMAR) BCVA improved significantly, and mean CMT and TMV were significantly reduced in the IVTA group compared with the laser,only group (controls) at all study follow-up visits (P < .001). The mean logMAR BCVA (Snellen equivalent) was 0.44 (20/50(-2)) for the IVTA group and 0.38 (20/50(+1)) for the controls at baseline, and 0.12 (20/25(-1)) for the IVTA group and 0.32 (20/40(-1)) for the controls at 12 months (P < .001.). The mean CMT and TMV were, respectively, 360 mu m and 8.59 mm(3) for the IVTA group and 331 mu m and 8.44 mm(3) for the controls at baseline, and 236 mu m and 7.32 mm(3) for the IVTA group and 266 mu m and 7.78 mm(3) for the controls at 12 months (P < .001). CONCLUSIONS: The combination of laser photocoagulation with IVTA was associated with improved BCVA and decreased CMT and TMV when compared with laser photocoagulation alone for the treatment of moderate PDR with CSME. (Am J Ophthalmol 2009;147:291-297. (C) 2009 by Elsevier Inc. All rights reserved.)