Real-Time Retinal Imaging with a Parallel OCT Using a CMOS Smart Array Detector

Optical coherence tomography (OCT) is a non-invasive interferometric imaging technique offering millimeter penetration depths of a sample with outstanding axial resolution. In this work a parallel Fourier domain optical coherence tomography (FD OCT) system is presented which records full tomograms of the sample structure in parallel. A fully parallel FD OCT system allows fast real time imaging of biological tissues.

Objective: Optic coherence tomography (OCT) is a contactless and fast neuroimaging method. Previous studies have observed thinning of the ganglion cell layer (GCL) and inner plexiform layer (IPL) in many neurodegenerative diseases. The aim of this study was to compare the GCL volume, retinal nerve fiber layer (RNFL), and IPL thickness in obsessive compulsive patients and controls using OCT to demonstrate neurodegeneration in obsessive compul-sive disorder (OCD). Methods: This study involved 50 OCD patients who were being followed by the Psychiatry Department of Adiyaman University Medical School and 50 healthy volunteers as control. OCT measurements were performed for both groups. The RNFL, IPL thickness, and GCL volumes were measured and recorded automatically by a spectral OCT device. Results: The RNFL thickness was lower in patients compared with controls at all mea-sured regions, and this decrease statistically significant in a few regions (left temporo-superior, left mean). The left and right choroid layer thickness acquired from three regions of choroid layer was higher in patients compared with controls. The GCL and IPL volumes were also significantly lower in the patient group. There was a significant negative correlation between the disease duration and OCT results. Discussion: These findings suggest that neurode-generation occurs during the course of OCD. This degeneration may be demonstrated by decreased GCL at early stages, and as the disease progresses, involvement of other retinal layers, such as the RNFL and IPL, may be observed.

Conventional optical coherence tomography (OCT) systems generally have a limited imaging range within a depth of only 1-2 mm and suffers from unwanted noise such as speckle, ghost or mirror noise. To overcome these limitations, we developed a motorized-stage-based OCT system with an extended imaging range, using a common-path Fourier-domain optical coherence tomography (CP-FD-OCT) configuration. Using this OCT systems, OCT image was obtained from an onion, and their subsurface structure were observed. The result showed that the OCT images obtained using our motorized-stage-based system had a significantly extended imaging range due to its real-time accurate depth tracking. Consequently, the devised CP-FD-OCT systems and algorithms have good potential for the further development of endoscopic OCT for microsurgery.

We present a three-dimensional (3-D) endoscopic optical coherence tomography (OCT) system based on a dual axis microelectromechanical system (MEMS) mirror. The diameter of MEMS mirror was 1.2 mm and both axes were capable of scanning up to 20° (optical) at greater than 1 kHz with excellent linearity. The MEMS mirror was packaged in a machined acrylic endoscopic housing which provided mechanical protection and electrical interconnects as well as optical alignment of the MEMS device to a focusing GRIN lens. The endoscopic MEMS probe was integrated and tested with both a fiber-based time domain (TD) OCT system and Fourier domain (FD) OCT system. Combining the 2-axis lateral scanning of the MEMS device with an axial scan allowed 3-D volume images to be obtained at a rate of 3 frames/s for the TD system and 7 frames/s for the FD system. In the initial investigations, in vivo 3-D OCT images of a human finger as well as images of animal tissue such as healthy rabbit trachea, normal and cancerous regions of hamster cheek pouch tissue were obtained. These images allowed real-time diagnosis of diseased tissue and also clearly delineated important features and tissue structures.

In recent years, optical coherence tomography (OCT) became gained importance in medical disciplines like ophthalmology, due to its noninvasive optical imaging technique with micrometer resolution and short measurement time. It enables e. g. the measurement and visualization of the depth structure of the retina. In other medical disciplines like dermatology, histopathological analysis is still the gold standard for skin cancer diagnosis. The EU-funded project VIAMOS (Vertically Integrated Array-type Mirau-based OCT System) proposes a new type of OCT system combined with micro-technologies to provide a hand-held, low-cost and miniaturized OCT system. The concept is a combination of full-field and full-range swept-source OCT (SS-OCT) detection in a multi-channel sensor based on a micro-optical Mirau-interferometer array, which is fabricated by means of wafer fabrication. This paper presents the study of an experimental proof-of-concept OCT system as a one-channel sensor with bulk optics. This sensor is a Linnik-interferometer type with similar optical parameters as the Mirau-interferometer array. A commercial wavelength tunable light source with a center wavelength at 845nm and 50nm spectral bandwidth is used with a camera for parallel OCT A-Scan detection. In addition, the reference microscope objective lens of the Linnik-interferometer is mounted on a piezo-actuated phase-shifter. Phase-shifting interferometry (PSI) techniques are applied for resolving the conjugate complex artifact and consequently contribute to an increase of image quality and depth range. A suppression ratio of the complex conjugate term of 36 dB is shown and a system sensitivity greater than 96 dB could be measured.

The aim of this study was to summarise existing findings regarding optical coherence tomography (OCT) measurements of ganglion cell layer (GCL) alterations in optic neuritis (ON) and multiple sclerosis (MS). Peer-reviewed studies published prior to April 2016 were searched using PubMed, EMBASE, Web of Science and Scopus. Studies were included if they measured GCL thickness using OCT in patients with either ON, MS or clinically isolated syndrome. For the meta-analysis, we compared GCL thickness in MS patients with and without prior ON, to healthy controls. 42/252 studies were reviewed. In acute ON, studies showed significant thinning of the GCL within the first 5weeks (n=5), earlier than retinal nerve fibre layer (RNFL) thinning. GCL thinning at 1-2months after acute ON predicted visual function at 6months (n=3). The meta-analysis showed that the thickness of the GCL was significantly reduced in MS patients both with and without previous ON compared to healthy controls. GCL thinning was associated with visual function in most studies (n=10) and expanded disability status scale (EDSS) scores (n=6). In acute ON, thinning of the GCL is measurable prior to RNFL thinning, and GCL thickness after 1-2months may predict visual function after 6months. Furthermore, GCL thinning occurs in MS both with and without prior ON, and may be associated with visual function and EDSS score. This suggests that the GCL is a promising biomarker, which may be used to examine in vivo neurodegeneration in ON and MS.

Background: Optical coherence tomography (OCT) is a noninvasive method of analyzing in vivo retinal architecture. It also measures retinal nerve fiber layer (RNFL) thickness, which is useful in managing diseases of the retina. Age-related thinning of the retinal ganglion cell complex has been measured using OCT. The present study is to evaluate the RNFL and ganglion cell layer (GCL) thickness using spectral domain OCT in patients with cognitive impairment (CI) and to study the correlation between RNFL and mini–mental state examination (MMSE) scores. Materials and Methods: A case–control study was done on 88 eyes of 44 patients, of which 27 belong to mild CI (MCI) and 17 were controls. They were assessed using MMSE/MINICOG/Montreal Cognitive Assessment tests and retinal OCT for RNFL, GCL, and inner plexiform layer (GCL + IPL) analysis. Results: RNFL thickness was reduced in all quadrants, more in superior and inferior quadrants in patients with MCI. GCL + IPL layer showed overall thinning in all quadrants, of which inferonasal and inferior quadrants were thinnest. Conclusion: MCI patients were prone to develop neurodegeneration even in the absence of microvascular changes in the retina. Hence, it is suggested to carry out routine evaluation of retina with OCT in all patients above the age of 60 to detect early neurodegenerative changes for early management. It is also noted that the sensitivity of GC + IPL was higher than that of RNFL to discriminate MCI from controls.

Mild traumatic brain injury (mTBI) is common with many patients suffering disabling long-term sequelae, with visual symptoms frequently reported. There are no objective biomarkers of mTBI that are routinely used in clinical practice. Optical coherence tomography (OCT) has been used in mTBI research, as it enables visualisation of the neuroretina, allowing measurement of the retinal nerve fibre layer and ganglion cell layer. This systematic review aims to appraise the available literature and assess whether there are significant changes within the retinal nerve fibre layer and ganglion cell layer in subjects after mTBI. A systematic review was carried out in accordance with PRISMA guidelines and registered with PROSPERO (Number: CRD42022360498). Four databases were searched for relevant literature published from inception until 1 September 2022. s and full texts were screened by three independent reviewers. Initial screening of databases yielded 341 publications, of these, three fulfilled all the criteria for inclusion. All three studies showed thinning of the retinal nerve fibre layer, whereas there were no significant changes in the ganglion cell layer. This systematic review demonstrated that thinning of the retinal nerve fibre layer (but not of the ganglion cell layer) is associated with mTBI. It provides preliminary evidence for the use of the retinal nerve fibre layer as a potential biomarker of damage to the visual system in mTBI. Further prospective longitudinal studies ensuring uniform diagnosis and accurate phenotyping of mTBI are needed to understand the effects on the visual system and potential of OCT as a prognostic biomarker.

A swept-source optical coherence tomography (OCT) system using mid-infrared light is demonstrated using commercially available light source and photodetectors. The light source is a tunable external cavity quantum cascade laser (QCL) with four laser modules and a wavelength range of 5.4μm – 12.8μm. The laser output is pulsed and has a maximum allowable duty cycle of 8%. A thermoelectrically cooled photovoltaic detector with a peak sensitivity at 8μm is configured in a Michelson interferometer setup. Noise from three sources are characterized: the analogue-to-digital converter (ADC), the detectors and the relative intensity noise (RIN). The ADC and the detector have a noise spectral density of 2.8 pW/√Hz and 21.4 pW/√Hz over a bandwidth of 100 MHz respectively; the value of RIN is -102 dB/Hz. The OCT system is used to collect the reflectivity profile of a mirror, which is measured with a signal to noise ratio (SNR) of 17.5 dB. Decreasing the time of sweep from 1s to 200ms has the effect of reducing the SNR by 4 dB.

IMPACT: Despite its importance in systemic diseases such as diabetes, the eye is notably difficult to examine for non-specialists; this study introduces a fully automated approach for eye disease screening, coupling a deep learning algorithm with a robotically-aligned optical coherence tomography system to improve eye care in non-ophthalmology settings. OBJECTIVES/GOALS: This study aims to develop and test a deep learning (DL) method to classify images acquired from a robotically-aligned optical coherence tomography (OCT) system as normal vs. abnormal. The long-term goal of our study is to integrate artificial intelligence and robotic eye imaging to fully automate eye disease screening in diverse clinical settings. METHODS/STUDY POPULATION: Between August and October 2020, patients seen at the Duke Eye Center and healthy volunteers (age ≥18) were imaged with a custom, robotically-aligned OCT (RAOCT) system following routine eye exam. Using transfer learning, we adapted a preexisting convolutional neural network to train a DL algorithm to classify OCT images as normal vs. abnormal. The model was trained and validated on two publicly available OCT datasets and two of our own RAOCT volumes. For external testing, the top-performing model based on validation was applied to a representative averaged B-scan from each of the remaining RAOCT volumes. The model’s performance was evaluated against a reference standard of clinical diagnoses by retina specialists. Saliency maps were created to visualize the areas contributing most to the model predictions. RESULTS/ANTICIPATED RESULTS: The training and validation datasets included 87,697 OCT images, of which 59,743 were abnormal. The top-performing DL model had a training accuracy of 96% and a validation accuracy of 99%. For external testing, 43 eyes of 27 subjects were imaged with the robotically-aligned OCT system. Compared to clinical diagnoses, the model correctly labeled 18 out of 22 normal averaged B-scans and 18 out of 21 abnormal averaged B-scans. Overall, in the testing set, the model had an AUC for the detection of pathology of 0.92, an accuracy of 84%, a sensitivity of 86%, and a specificity of 82%. For the correctly predicted scans, saliency maps identified the areas contributing most to the DL algorithm’s predictions, which matched the regions of greatest clinical importance. DISCUSSION/SIGNIFICANCE OF FINDINGS: This is the first study to develop and apply a DL model to images acquired from a self-aligning OCT system, demonstrating the potential of integrating DL and robotic eye imaging to automate eye disease screening. We are working to translate this technology for use in emergency departments and primary care, where it will have the greatest impact.

PurposeTo assess the differences in the retina nerve fiber layer (RNFL) and the ganglion cell layer (GCL) in subjects with multiple sclerosis (MS) versus subjects diagnosed as clinically isolated syndrome (CIS).Methods58 eyes of healthy controls, 67 eyes of MS patients (<10 years) and 10 eyes of patients diagnosed with CIS (<10 years) were included in the study. Measurements were taken using the Posterior Pole Retinal Thickness Map protocol [shows the thickness of the retina throughout the posterior pole (volumetric examination of 30° × 25° OCT]) with the Heidelberg Spectralis optical coherence tomography (OCT) device. We analyzed the 8x8 grid placed along the fovea symmetrically with the papilla. We analyzed the average thickness of the RNFL and the GCL in the 64 cells obtained.ResultsBoth groups, EM and CIS, present a significant thinning of the RNFL (27 and 32 cells respectively) and the GCL (45 and 20 cells respectively) with respect to the healthy controls. On the other hand, there has been a significant thinning of the RNFL in patients with MS (9 cells) versus GCL and a slightly significant thinning of the GCL (3 cells) in MS patients with CIS.ConclusionsOCT is able to detect significant changes in the retina of patients who do not meet dissemination criteria in time and space for the diagnosis of MS. These CIS patients present a significant thinning of the RNFL and the GCL with respect to healthy controls and there are slightly differences between MS and CIS in the RNFL and the GCL.

To investigate the early and late stages of posterior vitreous detachment (PVD) in the foveal area in correlation with age and gender. Three hundred and thirty-five emmetropic eyes of 271 Caucasian patients (216 women/119 men) were examined by optical coherence tomography (OCT) and ultrasound (US). Eyes were classified into groups according to the patients age (up to 69.9; 70-74.9; 75-79.9; over 80 years) and to the clinical findings [Vitreous state: Detached in US; Detached in OCT; Foveal adhesion (FA); Attached vitreous]. The mean age was 76 ± 8 ranging from 44 to 89 years in female and 72 ± 10 ranging from 46 to 87 years in male subjects. The vitreous was attached in 32% of all eyes, 18.5% had FA, 18.5% were detached in OCT and 68% were detached in US. While prevalence of FA decreases with increasing age, OCT-diagnosed detachments did not change significantly with age. Between the ages of 70 and 75, an increase in PVD rates occurred. The prevalence of PVD was similar in both genders. Women were significantly older than men in the late-stage PVD in the eyes. The use of OCT and US enabled us to detect a partial or total PVD in 80% of the eyes. A sudden increase in late-stage PVD between the ages of 70 and 75 was observed, correlating with the reported age prevalence of various macular diseases. In contrast to myopics, both genders of elderly emmetropics have a similar prevalence of PVD.

The non-classic presentation of paediatric celiac disease (CeD) becomes increasingly common in daily practice, which requires an awareness of eye findings. The purpose of this study was to evaluate eye involvement and effect of gluten-free diet on ocular involvement in paediatric CeD patients by measuring the thicknesses of choroid and ganglion cell complex (GCC) composed of retinal nerve fibre layer, ganglion cell layer and inner plexiform layer using enhanced depth imaging optical coherence tomography. Forty-three CeD patients aged between four and 16years (mean age: 9.9±4.1, 12 boys and 31 girls) and 48 healthy children (mean age: 11.3±4.1,17 boys and 31 girls) were compared. Following comprehensive eye examinations, thicknesses of choroid at three points and GCC layers (retinal nerve fibre layer at five points, ganglion cell layer and inner plexiform layer) were obtained using enhanced depth imaging optical coherence tomography. Measurement of thicknesses of choroid and GCC layers by a trained optical coherence tomography technician and an ophthalmologist who were not aware about group of children in paediatric CeD patients with 1year gluten-free diet was carried out. All layers of subfoveal, nasal and temporal choroid were significantly thinner in CeD than in the control group (P<.001, all, respectively). No significant difference was observed between the CeD and control groups in terms of GCC thicknesses (P>.05, all, respectively). Paediatric CeD caused thinning of subfoveal, nasal and temporal areas of choroid, and this change is apparent even after 1year gluten-free diet. This eye involvement should be more closely screened at diagnosis, and long-term clinical results of thin choroid should be determined. Thicknesses of GCC layers were not different in CeD group and may reveal the effect of diet or not involvement.

Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized as a condition with both neurodevelopmental and neurodegenerative components. This study aims to investigate retinal structural alterations in adults diagnosed with ADHD using optical coherence tomography (OCT) and to identify potential retinal biomarkers. The study included 31 adults diagnosed with ADHD according to DSM-5 criteria and 33 age- and sex-matched healthy controls. Retinal measurements were obtained from the right eye of all participants using the Spektralis® OCT system in accordance with the ETDRS protocol. Retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), ganglion cell complex (GCC), and central macular thickness (CMT) were measured. ADHD symptom severity was assessed using the Adult ADHD Self-Report Scale (ASRS). Group comparisons were made using independent t-tests, and correlations with clinical measures were evaluated using Pearson correlation analysis. Compared to healthy controls, the ADHD group showed a statistically significant thinning in the CMT, IPL, and GCC layers, especially at the 1 mm zone (p < 0.05). CMT (254.3 µm vs. 268.7 µm), IPL (35.2 µm vs. 38.4 µm), and GCC (78.5 µm vs. 82.3 µm). Similar thinning patterns were observed at the 3 mm zone for CMT and GCC, and at the 6 mm zone for IPL. No statistically significant differences were found in RNFL and GCL measurements. Thinning in specific retinal layers was significantly correlated with higher ADHD severity scores. Our study demonstrates that adults with ADHD exhibit measurable retinal thinning, particularly in the CMT, IPL, and GCC layers. These structural changes may reflect underlying neurodegenerative processes and suggest that retinal imaging via OCT could serve as a useful non-invasive biomarker in adult ADHD.

We present optical coherence quantitation technique to monitor the redox state of mitochondria enzyme Cytochrome oxidase (CytOx) in bone tissue by the use of optical coherence tomography (OCT) system. Superluminescent diode (SLD) with its peak emission wavelength ((lambda) = 820nm) on the absorption band of oxidized form of CytOx was used in the experiments. The reflectance returning from the liquid phantoms (naphthol green B with intralipid) and bone tissue specimens (periosteum of calvaria from newborn rats) as a function of penetration depth was used to quantify the absorption changes of the sample. Absorption coefficients of naphthol green B were accurately quantified by the linear relationship between attenuation coefficients from the slopes of the reflected signals and naphthol green B concentration. The results show that the attenuation coefficient decreases in periosteums as CytOx is reduced by sodium dithionite, demonstrating the feasibility of this method to quantify the redox state of tissues studied. A 70% +/- 7% (n=4) reduction of attenuation coefficients in periosteums was clearly observed with redox change of CytOx after 5 min reduction. In addition, the results demonstrate that the OCT system is also capable of imaging the calvaria tomographically with a resolution at 9 microns, which could only be previously obtained by the conventional excisional biopsy.