Spectral-domain Optical Coherence Tomography Technology Research Articles

Noninvasive Diagnosis of Regional Alteration of Retinal Morphology and Structure with Optical Coherence Tomography in Rodents.

Spectral-domain optical coherence tomography (SD-OCT) produces high-resolution images of retinal cross sections and is becoming a method of choice for in vivo analyses of retinal morphology in rodents. We have adopted this technology to identify and analyze alterations of retinal structure, particularly those with regional and subtle changes. In this technical brief, we will demonstrate the use of SD-OCT in identifying subtle changes in retinal structure and morphology due to the effect of mosaic gene deletion in conditional knockout mice and of uneven distribution of intravitreally delivered compounds, review the application of SD-OCT in measuring pathological lesion volumes, and discuss the major benefits of SD-OCT technology over the traditional histological methods.

The association between retinal nerve fibre layer thickness and corpus callosum index in different clinical subtypes of multiple sclerosis.

The objective of this paper is to evaluate the association between physical disability in multiple sclerosis (MS) patients, the thickness of the retinal nerve fibre layer (RNFL) and corpus callosum volumes, as expressed by the corpus callosum index (CCI). This study was based on a cohort of 212 MS patients and 52 healthy control subjects, who were age and gender matched. The MS patients included 144 women and 177 relapsing-remitting MS (RRMS) patients. Peripapillary and volumetric optical coherence tomography (OCT) scans of the macula were performed using spectral-domain OCT technology. All magnetic resonance imaging (MRI) scans were performed using 1.5-T systems. CCI and RNFL were lower in MS than healthy control subjects (0.341 versus 0.386, p<0.01 and 92.1 versus 105.0, p<0.01). In addition, CCI correlated with RNFL (r=0.464, p<0.01). This was also true for the subgroup of patients with no history of optic neuritis (ON). There is a correlation between the thickness of the RNFL and CCI values in MS patients with no history of ON, which suggests that OCT might be a suitable marker for neurodegeneration in MS clinical trials.

Macular SD-OCT Outcome Measures: Comparison of Local Structure-Function Relationships and Dynamic Range

PurposeWe tested the hypothesis that the macular ganglion cell layer (GCL) thickness demonstrates a stronger structure-function (SF) relationship and extends the useful range of macular measurements compared with combined macular inner layer or full thickness.MethodsNinety-eight glaucomatous eyes and eight normal eyes with macular spectral domain optical coherence tomography (SD-OCT) volume scans and 10-2 visual fields were enrolled. Inner plexiform layer (IPL), GCL, macular retinal nerve fiber layer (mRNFL), ganglion cell-inner plexiform layer (GCIPL), ganglion cell complex (GCC), and full thickness (FT) measurements were calculated for 8 × 8 arrays of 3° superpixels. Main outcome measures were local structure-function relationships between macular superpixels and corresponding sensitivities on 10-2 fields after adjusting for ganglion cell displacement, dynamic range of measurements, and the change point (total deviation value where macular parameters reached measurement floor).ResultsMedian (interquartile range [IQR]) mean deviation was −7.2 (−11.6 to −3.2) dB in glaucoma eyes. Strength of SF relationships was highest for GCIPL, GCL, GCC, and IPL (ρ = 0.635, 0.627, 0.621, and 0.577, respectively; P ≤ 0.046 for comparisons against GCIPL). Highest SF correlations coincided with the peak of GCL thickness, where the dynamic range was widest for FT (81.1 μm), followed by GCC (65.7 μm), GCIPL (54.9 μm), GCL (35.2 μm), mRNFL (27.5 μm), and IPL (20.9 μm). Change points were similar for all macular parameters (−7.8 to −8.9 dB).ConclusionsGCIPL, GCL, and GCC demonstrated comparable SF relationships while FT, GCC, and GCIPL had the widest dynamic range. Measurement of GCL did not extend the range of useful structural measurements. Measuring GCL does not provide any advantage for detection of progression with current SD-OCT technology.

Current interpretation of optical coherence tomography in the posterior pole

ObjectiveTo review the literature in order to describe the current nomenclature for the interpretation of retinal images of optical coherence tomography (OCT) in the macular area. MethodsA comprehensive literature search was conducted in the major biomedical databases since the introduction of OCT in ophthalmological field. ResultsQuantitative variations of central macular thickness and proper terminology used throughout the years are directly related to the technology and equipment used. ConclusionsThe current nomenclature of normal macular architecture represented in vivo on spectral domain OCT technology provides a clear and valid anatomical interpretation that can be applied, not only in research, but also in everyday practice.

Interpretación actual de la tomografía de coherencia óptica en el polo posterior

ObjectiveTo review the literature in order to describe the current nomenclature for the interpretation of retinal images of optical coherence tomography (OCT) in the macular area. MethodsA comprehensive literature search was conducted in the major biomedical databases since the introduction of OCT in ophthalmological field. ResultsQuantitative variations of central macular thickness and proper terminology used throughout the years are directly related to the technology and equipment used. ConclusionsThe current nomenclature of normal macular architecture represented in vivo on spectral domain OCT technology provides a clear and valid anatomical interpretation that can be applied, not only in research, but also in everyday practice.

Acute optic neuritis: a clinical paradigm for evaluation of neuroprotective and restorative strategies?

What makes the acute optic neuritis model unique in an era of trials for neuroprotective and myelin repair agents? Acute optic neuritis (AON) is a common, and often the earliest manifestation of central nervous system (CNS) inflammatory demyelinating disorders like multiple sclerosis (MS) and neuromyelitis optica (NMO). It affects at least half the patients with MS and is the presenting feature in 15–20% of patients. Vision loss in AON secondary to NMO tends to be more severe with less potential for recovery and greater axonal degeneration, as measured by optical coherence tomography (OCT) (Bennett et al., 2014). Several unique features of the afferent visual pathway (AVP) make the AON model an ideal system to study disease pathogenesis and evaluate potential neuroprotective and myelin repair strategies.

Effect of the blue filter intraocular lens on the progression of geographic atrophy.

To clinically evaluate the effect of blue light-filtering intraocular lenses (IOLs) on disease progression in patients with geographic atrophy (GA). Clinical data from 66 eyes of 40 patients were investigated, 27 with a blue filter and 39 with a non-blue filter IOL. Spectral-domain optical coherence tomography technology and the advanced retinal pigment epithelium analysis software tool were used to measure lesion size and monitor its progression over 1 year. The mean and median baseline area of GA for the total sample was 5.55 ± 4.72 mm2 and 4.40 mm2, respectively. There was a statistically significant difference of the mean (p = 0.0002) and median (p&lt;0.0001) GA progression in 1 year between the blue filter and non-blue filter IOL group (0.72 ± 0.39 SD mm2 mean and 0.70 mm2 median compared to 1.48 ± 0.88 SD mm2 and 1.30 mm2, respectively). The clinical data strongly support a photoprotective role of blue light-filtering IOLs on the progression of the atrophic form of dry age-related macular degeneration after cataract surgery.

Lrit3 Deficient Mouse (nob6): A Novel Model of Complete Congenital Stationary Night Blindness (cCSNB)

Mutations in LRIT3, coding for a Leucine-Rich Repeat, immunoglobulin-like and transmembrane domains 3 protein lead to autosomal recessive complete congenital stationary night blindness (cCSNB). The role of the corresponding protein in the ON-bipolar cell signaling cascade remains to be elucidated. Here we genetically and functionally characterize a commercially available Lrit3 knock-out mouse, a model to study the function and the pathogenic mechanism of LRIT3. We confirm that the insertion of a Bgeo/Puro cassette in the knock-out allele introduces a premature stop codon, which presumably codes for a non-functional protein. The mouse line does not harbor other mutations present in common laboratory mouse strains or in other known cCSNB genes. Lrit3 mutant mice exhibit a so-called no b-wave (nob) phenotype with lacking or severely reduced b-wave amplitudes in the scotopic and photopic electroretinogram (ERG), respectively. Optomotor tests reveal strongly decreased optomotor responses in scotopic conditions. No obvious fundus auto-fluorescence or histological retinal structure abnormalities are observed. However, spectral domain optical coherence tomography (SD-OCT) reveals thinned inner nuclear layer and part of the retina containing inner plexiform layer, ganglion cell layer and nerve fiber layer in these mice. To our knowledge, this is the first time that SD-OCT technology is used to characterize an animal model for CSNB. This phenotype is noted at 6 weeks and at 6 months. The stationary nob phenotype of mice lacking Lrit3, which we named nob6, confirms the findings previously reported in patients carrying LRIT3 mutations and is similar to other cCSNB mouse models. This novel mouse model will be useful for investigating the pathogenic mechanism(s) associated with LRIT3 mutations and clarifying the role of LRIT3 in the ON-bipolar cell signaling cascade.

Calibration-free B-scan images produced by master/slave optical coherence tomography

We report on a novel method to produce B-scan images in spectral domain optical coherence tomography (SD-OCT). The method proceeds in two steps. In the first step, using a mirror in the sample arm of the interferometer, channelled spectra are acquired for different values of the optical path difference (OPD) and stored as masks. In the second step, the mirror is replaced with an object and the captured channelled spectrum is correlated with each mask, providing the interference strength from the OPD value used to collect the respective mask. Such a procedure does not require data organized in equal frequency slots, and therefore there is no need for resampling as practiced in the conventional fast Fourier transform (FFT)-based SD-OCT technology. We show that the sensitivity drop-off versus OPD and the quality of B-scan images of the novel method are similar to those obtained in the conventional FFT-based SD-OCT, using spectral data linearly organized in frequency.

Optical Coherence Tomography in Pediatric Ophthalmology: Current Roles and Future Directions

The application of existing optical coherence tomography (OCT) technology to the pediatric population is limited in both the design specification of the device and its hardware. However, the potential of OCT in the pediatric population has not been fully realized. The authors review the literature, highlighting the currently available spectral-domain OCT technology and summarizing the reported normal pediatric OCT parameters for retinal nerve fiber layer and macular thickness. They also review the pediatric ophthalmological conditions in which OCT has been used and discuss advancements in OCT design and their potential applications to the pediatric population. The use of OCT in pediatric populations is likely to increase greatly in the coming years, aiding clinical decision-making and providing new insights into pediatric disease pathophysiology.

The comparison of manual vs automated disc margin delineation using spectral-domain optical coherence tomography

To examine the impact of manual vs automated disc margin delineation on optic nerve head (ONH) and retinal nerve fiber layer (RNFL) parameters using spectral-domain optical coherence tomography (SDOCT). A prospective cohort study consisting of normal, glaucoma suspect (GS) and glaucoma patients who underwent ONH and RNFL measurements using SDOCT technology (RTVue; Optovue Inc.). The retinal pigment epithelium/Bruch's membrane (RPE/BM) complex end points were automatically determined first, and were manually redefined subsequently. Analysis of variance, coefficient of variation (COV), concordance correlation coefficient (CCC), and Bland-Altman plots were used for the analyses. Ninety-nine eyes of 50 subjects (age 68±10 years) consisting of 36 glaucoma, 56 GS, and 7 normal eyes were included. The RNFL thickness measurements were similar (P>0.05) between the two methods of demarcation, except for the inferior-nasal sector (P=0.04). For the ONH measurements, the cup-to-disc (C/D) ratio and rim area showed significant differences between the two methods (P<0.001). COV/CCC values for the ONH parameters were as follows: cup area 17.6%/0.88; cup volume 7.4%/0.91; average C/D ratio 18.1%/0.78; rim area 25.3%/0.69; and rim volume 42.6%/0.71, respectively. CCC/COV values for the RNFL parameters were as follows: average 2.1%/0.98; inferior-temporal quadrant 8.1%/0.79; inferior-nasal quadrant INQ quadrant 12.6%/0.67; SNQ quadrant 7.8%/0.83; and STQ quadrant 7.8%/0.88, respectively. An overall high agreement and moderate-substantial concordance was observed between the demarcation methods. Automated disc margin delineation of SDOCT can be used reliably in clinical practice.

Comparison of VEP with contrast sensitivity and other measurements of central visual function

In order to evaluate alternative visual acuity testing techniques, especially to discriminate between small changes and for high visual acuity, we conducted a study covering several state-of-the-art techniques. In this cross-sectional study, a homogeneous cohort of healthy and young patients (n = 33; 66 eyes) underwent ETDRS vision acuity (VA) testing, testing for contrast sensitivity (CS), VA determination with spatial frequency sweep visual evoked potentials (VEP) and a series of examinations of perifoveal retinal nerve fibre layer thickness (RNFLT) using Spectralis SD-OCT. To simulate the effect of artificial media opacity, CS, and VEP were repeated with Bangerter foils. We found that Bangerter foils can be used to reduce VA effectively measured by VA testing and VEP VA. CS correlated significantly with VA (correlation coefficients ranging from 0.54 to 0.77). VEP may be used to estimate VA; nevertheless, we found no significant correlation. RNFLT did not correlate significantly with VA. CS seems to correlate well with VA when used for high VA. All other used examinations seem to have difficulties distinguishing between small differences in VA or when the VA is high.

Loss of retinal nerve fibre layer axons indicates white but not grey matter damage in early multiple sclerosis

Optical coherence tomography (OCT) has shown thinning of the retinal nerve fibre layer (RNFL) and total macular volume (TMV) in multiple sclerosis (MS) patients. Measures of retinal atrophy are associated with the brain parenchymal fraction (BPF) assessed by magnetic resonance imaging (MRI). However, in MS, data on the relation of OCT measures and grey and white matter volumes are contradictory. We performed a prospective cross-sectional study with a statistically pre-defined endpoint to test our hypothesis that OCT measures of neuro-axonal degeneration are related to global and partial brain atrophy in early forms of MS. Forty-four patients with clinically isolated syndrome (n = 10) or relapsing-remitting MS (n = 34; mean disease duration = 3.2 years, median EDSS = 1.5) were enrolled in the study. Peripapillary- and volumetric OCT scans of the macula were performed using latest spectral-domain OCT technology. BPF as well as white and grey matter fractions (WMF/GMF) were assessed by 1.5 Tesla MRI scans. Generalized estimating equation models adjusted for age and linear regression statistics were used to assess the association between OCT and MRI measures. RNFL thickness, TMV and age were significantly associated with BPF. RNFL thickness and TMV independently predicted WMF (P = 0.003 and P = 0.032) but not GMF (P = 0.717 and P = 0.357) when corrected for age. In contrast, age was strongly associated with GMF (P < 0.001) but not WMF. Our study suggests that, in early MS, OCT measures of retinal atrophy are related to volumetric changes in the white but not grey matter compartment as assessed by MRI. It further substantiates the association of retinal thinning and brain tissue loss in MS.

The Antiangiogenic Effects of Integrin α5β1 Inhibitor (ATN-161) In Vitro and In Vivo

Integrin α5β1 is involved in the development of choroidal neovascularization (CNV). Thus, the inhibition of integrin α5β1 may provide an alternative to the current standard of CNV therapy, which involves inhibition of vascular endothelial growth factor (VEGF) and is not effective in all patients. This study evaluated the antiangiogenic effects of ATN-161, a small peptide inhibitor of integrin α5β1, in human choroidal endothelial cells (hCECs) and in laser-induced CNV in rats. Furthermore, the utility of spectral-domain optical coherence tomography (SD-OCT) for dynamic observation of the development of CNV in animal models was assessed. The antiangiogenic potential of ATN-161 was evaluated in VEFG-stimulated hCECs by MTS proliferation assays, migration assays, and synthetic matrix capillary tube formation assays. To evaluate the antiangiogenic effects of ATN-161 in vivo, CNV was induced in rats by laser photocoagulation. ATN-161, scrambled peptide, or AF564 anti-VEGF antibody, were injected intravitreally immediately after photocoagulation. Eyes were examined by SD-OCT and fluorescein angiography on days 1, 7, and 14 after injection, and the areas of CNV were measured by analysis of choroidal flatmounts at day 14. ATN-161 inhibited VEGF-induced migration and capillary tube formation in hCECs, but did not inhibit proliferation. In vivo, injection of ATN-161 after laser photocoagulation inhibited CNV leakage and neovascularization to an extent similar to AF564. Furthermore, SD-OCT and histologic examinations indicated that ATN-161 significantly decreased the size of laser-induced lesions. Integrin α5β1 inhibition by ATN-161 may be a promising alternative therapy for CNV-related angiogenesis. In addition, SD-OCT technology allows excellent visualization of experimentally induced CNV in vivo.

Evaluation of anterior‐segment inflammation and retinal thickness change following cataract surgery

To investigate the physiological retinal response to uneventful cataract surgery using conventional time-domain (TD-OCT) and current spectral-domain optical coherence tomography (SD-OCT) in combination with an assessment of the anterior chamber inflammatory reaction by laser flare/cell meter (LCFM). Thirty-four patients scheduled for cataract surgery were included in this prospective pilot study. Retinal parameters were examined according to a standardized examination procedure using TD-OCT (Stratus; Carl Zeiss Meditec, Dublin, California, USA) and SD-OCT (Cirrus; Carl Zeiss Meditec) devices. The inflammatory reaction of the anterior chamber was measured by LFCM (Kowa FC-1000, Kowa Co. Ltd, Tokyo, Japan). Examinations were carried out preoperatively and at day 2, week 1 and week 4 postoperatively. A slight decrease of central retinal thickness values was identified at day 2 postoperatively followed by an increase of these parameters at week 4. LFCM showed peak values in all patients at day 2 postoperatively with a constant decrease at the following visits. No visible pathological retinal changes were seen after surgery. A biphasic retinal response after surgery could be shown with SD-OCT and TD-OCT technology. By using the advantages of rasterscanning mode, SD-OCT technology is superior to TD-OCT imaging in the investigation of the physiological retinal response to cataract surgery.

Spectral Domain Optical Coherence Tomography in the Diagnosis and Management of Glaucoma

Spectral domain optical coherence tomography (SD-OCT) is a relatively new imaging technology that is being used for the diagnosis and management of glaucoma. This article presents a review of the specific parameters analyzed by SD-OCT and the diagnostic capability, reproducibility, and limitations of the device. SD-OCT parameters useful for diagnosis of glaucoma include retinal nerve fiber layer analysis, optic nerve head analysis, and ganglion cell complex analysis. These parameters have proven to be at least as equivalent to time-domain technology in terms of diagnostic capability and superior in terms of reproducibility. SD-OCT technology may be limited by signal quality, image artifact, and confounding ocular disease.