Retinal layer measurements after successful macula-off retinal detachment repair using optical coherence tomography

PURPOSE Optical coherence tomography (OCT) was used to analyze the thickness of various retinal layers of patients following successful macula-off retinal detachment (RD) repair. METHODS Optical coherence tomography scans of patients after successful macula-off RD repair were reanalyzed with a subsegmentation algorithm to measure various retinal layers. Regression analysis was performed to correlate time after surgery with changes in layer thickness. In addition, patients were divided in two groups. Group 1 had a follow-up period after surgery of up to 7 weeks (range, 21-49 days). In group 2, the follow-up period was >8 weeks (range, 60-438 days). Findings were compared to a group of age-matched healthy controls. RESULTS Correlation analysis showed a significant positive correlation between inner nuclear-outer plexiform layer (INL-OPL) thickness and time after surgery (P=0.0212; r2=0.1551). Similar results were found for the ellipsoid zone-retinal pigment epithelium complex (EZ-RPE) thickness (P=0.005; r2=0.2215). Ganglion cell-inner plexiform layer thickness (GCL-IPL) was negatively correlated with time after surgery (P=0.0064; r2=0.2101). For group comparison, the retinal nerve fiber layer in both groups was thicker compared to controls. The GCL-IPL showed significant thinning in group 2. The outer nuclear layer was significantly thinner in groups 1 and 2 compared to controls. The EZ-RPE complex was significantly thinner in groups 1 and 2 compared to controls. In addition, values in group 1 were significantly thinner than in group 2. CONCLUSIONS Optical coherence tomography retinal layer thickness measurements after successful macular-off RD repair revealed time-dependent thickness changes. Inner nuclear-outer plexiform layer thickness and EZ-RPE thickness was positively correlated with time after surgery. Ganglion cell-inner plexiform layer thickness was negatively correlated with time after surgery.

Spectral-domain optical coherence tomography findings after severe exogenous endophthalmitis

PURPOSE To report outcomes and assess structural changes in the retina in patients with severe endophthalmitis. METHODS Retrospective, nonrandomized, interventional case series at a tertiary referral centre. Spectral domain optical coherence tomography (OCT) images of both eyes were acquired at least 5 months after pars plana vitrectomy. OCT images were analyzed using retinal layer segmentation. RESULTS Nine patients (46-80 years of age) were included in this study. Average ETDRS visual acuity before treatment was 23 letters and improved to 74 letters. In our cohort we did not find a generalized reduction of retinal layers using automated layer segmentation. CONCLUSION Our findings suggest that prompt treatment of severe endophthalmitis with intravitreal antibiotics followed by pars plana vitrectomy may lead to excellent visual outcomes with minimal damage to the retinal architecture.

Automatic estimation of noise parameters in Fourier-domain optical coherence tomography cross sectional images using statistical information

We present an application and sample independent method for the automatic discrimination of noise and signal in optical coherence tomography Bscans. The proposed algorithm models the observed noise probabilistically and allows for a dynamic determination of image noise parameters and the choice of appropriate image rendering parameters. This overcomes the observer variability and the need for a priori information about the content of sample images, both of which are challenging to estimate systematically with current systems. As such, our approach has the advantage of automatically determining crucial parameters for evaluating rendered image quality in a systematic and task independent way. We tested our algorithm on data from four different biological and nonbiological samples (index finger, lemon slices, sticky tape, and detector cards) acquired with three different experimental spectral domain optical coherence tomography (OCT) measurement systems including a swept source OCT. The results are compared to parameters determined manually by four experienced OCT users. Overall, our algorithm works reliably regardless of which system and sample are used and estimates noise parameters in all cases within the confidence interval of those found by observers.

Real-time ultra-high optical coherence tomography monitoring of optical tissue effects caused by selective retina therapy

Purpose: Selective retina therapy (SRT) has shown great promise compared to conventional retinal laser photocoagulation as it avoids collateral damage and selectively targets the retinal pigment epithelium (RPE). Its use, however, is challenging in terms of therapy monitoring and dosage because an immediate tissue reaction is not biomicroscopically discernibel. To overcome these limitations, real-time optical coherence tomography (OCT) might be useful to monitor retinal tissue during laser application. We have thus evaluated a proprietary OCT system for its capability of mapping optical changes introduced by SRT in retinal tissue. Methods: Freshly enucleated porcine eyes, covered in DMEM upon collection were utilized and a total of 175 scans from ex-vivo porcine eyes were analyzed. The porcine eyes were used as an ex-vivo model and results compared to two time-resolved OCT scans, recorded from a patient undergoing SRT treatment (SRT Vario, Medical Laser Center Lübeck). In addition to OCT, fluorescin angiography and fundus photography were performed on the patient and OCT scans were subsequently investigated for optical tissue changes linked to laser application. Results: Biomicroscopically invisible SRT lesions were detectable in OCT by changes in the RPE / Bruch's complex both in vivo and the porcine ex-vivo model. Laser application produced clearly visible optical effects such as hyperreflectivity and tissue distortion in the treated retina. Tissue effects were even discernible in time-resolved OCT imaging when no hyper-reflectivity persisted after treatment. Data from ex-vivo porcine eyes showed similar to identical optical changes while effects visible in OCT appeared to correlate with applied pulse energy, leading to an additional reflective layer when lesions became visible in indirect ophthalmoscopy. Conclusions: Our results support the hypothesis that real-time high-resolution OCT may be a promising modality to obtain additional information about the extent of tissue damage caused by SRT treatment. Data shows that our exvivo porcine model adequately reproduces the effects occurring in-vivo, and thus can be used to further investigate this promising imaging technique.

The association between in-stent neoatherosclerosis and native coronary artery disease progression: a long-term angiographic and optical coherence tomography cohort study.

AIMS The purpose of the present study was to investigate the relationship between in-stent neoatherosclerosis (NA) and native atherosclerosis progression of untreated coronary segments. METHODS AND RESULTS In-stent NA was assessed by optical coherence tomography (OCT) among patients included in the SIRTAX-LATE OCT study 5 years after drug-eluting stent (DES) (sirolimus-eluting and paclitaxel-eluting stents) implantation. Neoatherosclerosis was defined as the presence of fibroatheroma or fibrocalcific plaque within the neointima of stented segments with a longitudinal extension >1.0 mm. Atherosclerosis progression in untreated native coronary segments was evaluated by serial quantitative coronary angiography (QCA). The change in minimal lumen diameter (MLD) was serially assessed within matched segments at baseline and 5-year angiographic follow-up. The key clinical endpoint was non-target lesion (non-TL) revascularization throughout 5 years. A total of 88 patients with 88 lesions were available for OCT analysis 5 years after DES implantation. In-stent NA was observed in 16% of lesions with the majority of plaques being fibroatheromas (11.4%) followed by fibrocalcific plaques (5.7%). A total of 704 non-TL segments were serially evaluated by QCA. Between baseline and 5-year follow-up, the reduction in MLD was significantly more pronounced in patients with NA (-0.25 mm, 95% CI -0.36 to -0.17 mm) when compared with patients without NA (-0.13 mm, 95% CI -0.17 to -0.10 mm, P = 0.002). Similarly, non-TL revascularization was more frequent in patients with NA (78.6%) when compared with patients without NA (44.6%, P = 0.028) throughout 5 years. CONCLUSIONS In-stent NA is more common among patients with angiographic and clinical evidence of native atherosclerosis progression suggesting similar pathophysiological mechanisms.SIRTAX trial is registered at http://www.clinicaltrials.gov/ct2/show/NCT00617084.

Time-Resolved Ultra–High Resolution Optical Coherence Tomography for Real-Time Monitoring of Selective Retina Therapy

Purpose: Selective retina therapy (SRT) is a novel treatment for retinal pathologies, solely targeting the retinal pigment epithelium (RPE). During SRT, the detection of an immediate tissue reaction is challenging as tissue effects remain limited to intracellular RPE photodisruption. Time-resolved ultra-high axial resolution optical coherence tomography (OCT) is thus evaluated for the monitoring of dynamic optical changes at and around the RPE during SRT. Methods: An experimental OCT system with an ultra-high axial resolution of 1.78 µm was combined with an SRT system and time-resolved OCT M-scans of the target area were recorded from four patients undergoing SRT. OCT scans were analyzed and OCT morphology was correlated with findings in fluorescein angiography, fundus photography and cross-sectional OCT. Results: In cases where the irradiation caused RPE damage proven by fluorescein angiography, the lesions were well discernible in time-resolved OCT images but remained invisible in fundus photography and cross-sectional OCT acquired after treatment. If RPE damage was introduced, all applied SRT pulses led to detectable signal changes in the time-resolved OCT images. The extent of optical signal variation seen in the OCT data appeared to scale with the applied SRT pulse energy. Conclusion: The first clinical results proved that successful SRT irradiation induces detectable changes in the OCT M-scan signal while it remains invisible in conventional ophthalmoscopic imaging. Thus, real-time high-resolution OCT is a promising modality to monitor and analyze tissue effects introduced by selective retina therapy and may be used to guide SRT in an automatic feedback mode.

Quantitative Analysis of Mouse Retinal Layers Using Automated Segmentation of Spectral Domain Optical Coherence Tomography Images.

PURPOSE Quantification of retinal layers using automated segmentation of optical coherence tomography (OCT) images allows for longitudinal studies of retinal and neurological disorders in mice. The purpose of this study was to compare the performance of automated retinal layer segmentation algorithms with data from manual segmentation in mice using the Spectralis OCT. METHODS Spectral domain OCT images from 55 mice from three different mouse strains were analyzed in total. The OCT scans from 22 C57Bl/6, 22 BALBc, and 11 C3A.Cg-Pde6b(+)Prph2(Rd2) /J mice were automatically segmented using three commercially available automated retinal segmentation algorithms and compared to manual segmentation. RESULTS Fully automated segmentation performed well in mice and showed coefficients of variation (CV) of below 5% for the total retinal volume. However, all three automated segmentation algorithms yielded much thicker total retinal thickness values compared to manual segmentation data (P < 0.0001) due to segmentation errors in the basement membrane. CONCLUSIONS Whereas the automated retinal segmentation algorithms performed well for the inner layers, the retinal pigmentation epithelium (RPE) was delineated within the sclera, leading to consistently thicker measurements of the photoreceptor layer and the total retina. TRANSLATIONAL RELEVANCE The introduction of spectral domain OCT allows for accurate imaging of the mouse retina. Exact quantification of retinal layer thicknesses in mice is important to study layers of interest under various pathological conditions.

Long time remodeling during retinal degeneration evaluated by optical coherence tomography, immunocytochemistry and fundus autofluorescence

Purpose: To characterize the relationship between fundus autofluorescence (FAF), Optical Coherence Tomography (OCT) and immunohistochemistry (IHC) over the course of chronic retinal degeneration in the P23H rat. Methods: Homozygous albino P23H rats, Sprague–Dawley (SD) rats as controls and pigmented Long Evans (LE) rats were used. A Spectralis HRA OCT system was used for scanning laser ophthalmoscopy (SLO) imaging OCT and angiography. To determine FAF, fluorescence was excited using diode laser at 488 nm. A fast retina map OCT was performed using the optic nerve as a landmark. IHC was performed to correlate with the findings of OCT and FAF changes. Results: During the course of retinal degeneration, the FAF pattern evolved from some spotting at 2 months old to a mosaic of hyperfluorescent dots in rats 6 months and older. Retinal thicknesses progressively diminished over the course of the disease. At later stages of degeneration, OCT documented changes in the retinal layers, however, IHC better identified the cell loss and remodeling changes. Angiography revealed attenuation of the retinal vascular plexus with time. Conclusion: We provide for the first time a detailed long-term analysis of the course of retinal degeneration in P23H rats using a combination of SLO and OCT imaging, angiography, FAF and IHC. Although, the application of noninvasive methods enables longitudinal studies and will decrease the number of animals needed for a study, IHC is still an essential tool to identify retinal changes at the cellular level.

Functional Optical Coherence Tomography: In Vivo Applications in Dermatology and Neuroscience

Thesis (Ph.D.)--University of Washington, 2016-06

Fourier-domain optical coherence tomography: optimization of signal-to-noise ratio in full space

Optical coherence tomography (OCT) is an emerging coherence-domain technique capable of in vivo imaging of sub-surface structures at millimeter-scale depth. Its steady progress over the last decade has been galvanized by a breakthrough detection concept, termed spectral-domain OCT, which has resulted in a dramatic improvement of the OCT signal-to-noise ratio of 150 times demonstrated for weakly scattering objects at video-frame-rates. As we have realized, however, an important OCT sub-system remains sub-optimal: the sample arm traditionally operates serially, i.e. in flying-spot mode. To realize the full-field image acquisition, a Fourier holography system illuminated with a swept-source is employed instead of a Michelson interferometer commonly used in OCT. The proposed technique, termed Fourier-domain OCT, offers a new leap in signal-to-noise ratio improvement, as compared to flying-spot OCT systems, and represents the main thrust of this paper. Fourier-domain OCT is described, and its basic theoretical aspects, including the reconstruction algorithm, are discussed. (C) 2004 Elsevier B.V. All rights reserved.

Signal-to-noise ratio study of full-field Fourier-domain optical coherence tomography

We report a new approach in optical coherence tomography (OCT) called full-field Fourier-domain OCT (3F-OCT). A three-dimensional image of a sample is obtained by digital reconstruction of a three-dimensional data cube, acquired with a Fourier holography recording system, illuminated with a swept source. We present a theoretical and experimental study of the signal-to-noise ratio of the 3F-OCT approach versus serial image acquisition (flying-spot OCT) approach. (c) 2005 Optical Society of America.

Developments in contact lens measurement:a comparative study of industry standard geometric inspection and optical coherence tomography

Purpose: The aim of this study was to compare a developmental optical coherence tomography (OCT) based contact lens inspection instrument to a widely used geometric inspection instrument (Optimec JCF), to establish the capability of a market focused OCT system. Methods: Measurements of 27 soft spherical contact lenses were made using the Optimec JCF and a new OCT based instrument, the Optimec is830. Twelve of the lenses analysed were specially commissioned from a traditional hydrogel (Contamac GM Advance 49%) and 12 from a silicone hydrogel (Contamac Definitive 65), each set with a range of back optic zone radius (BOZR) and centre thickness (CT) values. Three commercial lenses were also measured; CooperVision MyDay (Stenfilcon A) in −10D, −3D and +6D powers. Two measurements of BOZR, CT and total diameter were made for each lens in temperature controlled saline on both instruments. Results: The results showed that the is830 and JCF measurements were comparable, but that the is830 had a better repeatability coefficient for BOZR (0.065 mm compared to 0.151 mm) and CT (0.008 mm compared to 0.027 mm). Both instruments had similar results for total diameter (0.041 mm compared to 0.044 mm). Conclusions: The OCT based instrument assessed in this study is able to match and improve on the JCF instrument for the measurement of total diameter, back optic zone radius and centre thickness for soft contact lenses in temperature controlled saline.

Reproducibility-repeatability of choroidal thickness calculation using optical coherence tomography

Purpose. To evaluate the repeatability and reproducibility of subfoveal choroidal thickness (CT) calculations performed manually using optical coherence tomography (OCT). Methods. The CT was imaged in vivo at each of two visits on 11 healthy volunteers (mean age, 35.72 ± 13.19 years) using the spectral domain OCT. CT was manually measured after applying ImageJ processing filters on 15 radial subfoveal scans. Each radial scan was spaced 12° from each other and contained 2500 A-scans. The coefficient of variability, coefficient of repeatability (CoR), coefficient of reproducibility, and intraclass correlation coefficient determined the reproducibility and repeatability of the calculation. Axial length (AL) and mean spherical equivalent refractive error were measured with the IOLMaster and an open view autorefractor to study their potential relationship with CT. Results. The within-visit and between-visit coefficient of variability, CoR, coefficient of reproducibility, and intraclass correlation coefficient were 0.80, 2.97% 2.44%, and 99%, respectively. The subfoveal CT correlated significantly with AL (R = -0.60, p = 0.05). Conclusions. The subfoveal CT could be measured manually in vivo using OCT and the readings obtained from the healthy subjects evaluated were repeatable and reproducible. It is proposed that OCT could be a useful instrument to perform in vivo assessment and monitoring of CT changes in retinal disease. The preliminary results suggest a negative correlation between subfoveal CT and AL in such a way that it decreases with increasing AL but not with refractive error.

Femtosecond laser micro-inscription of optical coherence tomography resolution test artifacts

Optical coherence tomography (OCT) systems are becoming more commonly used in biomedical imaging and, to enable continued uptake, a reliable method of characterizing their performance and validating their operation is required. This paper outlines the use of femtosecond laser subsurface micro-inscription techniques to fabricate an OCT test artifact for validating the resolution performance of a commercial OCT system. The key advantage of this approach is that by utilizing the nonlinear absorption a three dimensional grid of highly localized point and line defects can be written in clear fused silica substrates.

Three-dimensional calibration targets for optical coherence tomography

The recent expansion of clinical applications for optical coherence tomography (OCT) is driving the development of approaches for consistent image acquisition. There is a simultaneous need for time-stable, easy-to-use imaging targets for calibration and standardization of OCT devices. We present calibration targets consisting of three-dimensional structures etched into nanoparticle-embedded resin. Spherical iron oxide nanoparticles with a predominant particle diameter of 400 nm were homogeneously dispersed in a two part polyurethane resin and allowed to harden overnight. These samples were then etched using a precision micromachining femtosecond laser with a center wavelength of 1026 nm, 100kHz repetition rate and 450 fs pulse duration. A series of lines in depth were etched, varying the percentage of inscription energy and speed of the translation stage moving the target with respect to the laser. Samples were imaged with a dual wavelength spectral-domain OCT system and point-spread function of nanoparticles within the target was measured.