We report a large field of view FOV low-cost smart fundus camera with non-mydriatic and spectral band illumination features for the purpose of diagnosing central nervous system diseases such as Alzheimer’s disease. By combining a customized optical lens group, ring light emitting diode light source, Li-battery, and Raspberry Pi we can port the spectrally selected light source through a 4 mm diameter pupil. Taking advantage of the open hardware platform and Linux operating system, we integrate two narrowband filters explicitly selected based on the unique spectrums of biomarkers (580 nm and 660 nm) with a Raspberry Pi camera module to obtain high quality images for the purpose of enhancing the visibility of retinal vasculature and nerve fiber layer.
The development of effective therapies for cognitive impairment (CI), especially due to Alzheimer’s disease, demands diagnosing the condition during the prodromal phase. The diagnosis of CI involves expensive and invasive methods, such as positron emission tomography and cerebrospinal fluid assessment via spinal tap. Hence, a comparatively lower cost and noninvasive method of diagnosis is imperative. The human retina is an extension of the brain characterized by similarities in vascular and neural structures. The complications of CI are not only limited to the brain but also affect the retina for which the loss of retinal ganglion cells has been associated with neurodegeneration in the brain. The loss of retinal ganglion cells in individuals with CI may be related to reduced vascular demand and a potential remodeling of the retinal vascular branching complexity. Retinal imaging biomarkers may provide a low cost and noninvasive alternative for the diagnosis of CI. In this study, the retinal vascular branching complexity of patients with CI was characterized using the singularity spectrum multifractal dimension and lacunarity parameter. A reduced vascular branching complexity was observed in subjects with CI when compared to age- and sex-matched cognitively healthy controls. Significant associations were also found between retinal vascular and functional parameters.
Reliable retinal layer thickness measurements using optical coherence tomography (OCT) are important to track the subtle retinal changes in longitudinal studies. A total of 10 eyes (5 healthy subjects, 40±13 years old) were enrolled to study the inter-session repeatability and identify the pitfalls affecting the reliabilities. Each eye was scanned using spectral domain OCT (Spectralis SDOCT, Heidelberg Engineering) for 3 sessions with 30 seconds rest in between. The first and second sessions were scanned independently and the third one was scanned with the first one as the baseline visit. Each session consisted of a confocal scanning laser ophthalmoscopy (cSLO) image and 61 B-scans of 496×768 pixels. The first, second and third sessions were named as baseline, unregistered and registered sessions; respectively. Seven retinal layers labeled as RNFL, GCL+IPL, INL, OPL, ONL, IS and OS were segmented using a custom software (OCTRIMA3D) and measured in the ETDRS grid. Inter-session standard deviation (σ), coefficient of repeatability (CR) and coefficient of variations (COV) were calculated to quantify the repeatability. Paired t-test of COVs was used to compare the repeatability and the level of significance was set at 5%. We obtained that values of the CR <5 μm and COV of 5%, were revealed only in the outer layers. The values of COV were not significantly different (p<0.05) in the unregistered scanning session. Our results show that the rotations in the unregistered scanning sessions do not cause significant change in repeatability.
This study is designed to test the repeatability of the quantitative analysis of intraretinal layer thickness and cup-disc ratio of the optic nerve head using ultra-high resolution optical coherence tomography (UHR-OCT). Group A, containing 23 eyes of 12 healthy subjects, was imaged twice and group B, containing eight eyes of four subjects, was imaged three times. Intraretinal layers were segmented manually and the cup-to-disc ratio of the optic nerve head was analyzed. Custom-built automatic segmentation software was also used to segment a set of images for comparison. A total of nine intraretinal layers were visualized and extracted manually. With group A, the central foveal thickness was 186.4 ± 15.9 μm (mean ± SD). The average retinal thickness was 296.4 ± 21.3 μm. The best repeatability, obtained when two repeated scans were taken, was obtained for the outer nuclear layer followed by the ganglion cell layer, the inner nuclear layer, the retinal nerve fiber layer and the worst was obtained for the outer segment. The intraclass correlation ranged from 0.824 to 0.997. The coefficients of repeatability ranged from 3.24 to 18.3 μm, corresponding to 1.47% to 26.20%. With group B, high interclass correlations were found and the automatic segmentation results were compatible with the manual results. Our results indicated that more retinal features might be imageable using UHR-OCT.
Purpose: To compare thickness measurements between Fourier-domain optical coherence tomography (FD-OCT) and time-domain OCT images analyzed with a custom-built OCT retinal image analysis software (OCTRIMA). Methods: Macular mapping (MM) by StratusOCT and MM5 and MM6 scanning protocols by an RTVue-100 FD-OCT device are performed on 11 subjects with no retinal pathology. Retinal thickness (RT) and the thickness of the ganglion cell complex (GCC) obtained with the MM6 protocol are compared for each early treatment diabetic retinopathy study (ETDRS)-like region with corresponding results obtained with OCTRIMA. RT results are compared by analysis of variance with Dunnett post hoc test, while GCC results are compared by paired t-test. Results: A high correlation is obtained for the RT between OCTRIMA and MM5 and MM6 protocols. In all regions, the StratusOCT provide the lowest RT values (mean difference 43 ± 8 μm compared to OCTRIMA, and 42 ± 14 μm compared to RTVue MM6). All RTVue GCC measurements were significantly thicker (mean difference between 6 and 12 μm) than the GCC measurements of OCTRIMA. Conclusion: High correspondence of RT measurements is obtained not only for RT but also for the segmentation of intraretinal layers between FD-OCT and StratusOCT-derived OCTRIMA analysis. However, a correction factor is required to compensate for OCT-specific differences to make measurements more comparable to any available OCT device.
We demonstrate quantitative analysis and error correction of optical coherence tomography (OCT) retinal images by using a custom-built, computer-aided grading methodology. A total of 60 Stratus OCT (Carl Zeiss Meditec, Dublin, California) B-scans collected from ten normal healthy eyes are analyzed by two independent graders. The average retinal thickness per macular region is compared with the automated Stratus OCT results. Intergrader and intragrader reproducibility is calculated by Bland-Altman plots of the mean difference between both gradings and by Pearson correlation coefficients. In addition, the correlation between Stratus OCT and our methodology-derived thickness is also presented. The mean thickness difference between Stratus OCT and our methodology is 6.53 µm and 26.71 µm when using the inner segment/outer segment (IS/OS) junction and outer segment/retinal pigment epithelium (OS/RPE) junction as the outer retinal border, respectively. Overall, the median of the thickness differences as a percentage of the mean thickness is less than 1% and 2% for the intragrader and intergrader reproducibility test, respectively. The measurement accuracy range of the OCT retinal image analysis (OCTRIMA) algorithm is between 0.27 and 1.47 µm and 0.6 and 1.76 µm for the intragrader and intergrader reproducibility tests, respectively. Pearson correlation coefficients demonstrate R2>0.98 for all Early Treatment Diabetic Retinopathy Study (ETDRS) regions. Our methodology facilitates a more robust and localized quantification of the retinal structure in normal healthy controls and patients with clinically significant intraretinal features.
We determine the reliability and reproducibility of retinal thickness measurements with a custom-built OCT retinal image analysis software (OCTRIMA). Ten eyes of five healthy subjects undergo repeated standard macular thickness map scan sessions by two experienced examiners using a Stratus OCT device. Automatic/semi automatic thickness quantification of the macula and intraretinal layers is performed using OCTRIMA software. Intraobserver, interobserver, and intervisit repeatability and reproducibility coefficients, and intraclass correlation coefficients (ICCs) per scan are calculated. Intraobserver, interobserver, and intervisit variability combined account for less than 5% of total variability for the total retinal thickness measurements and less than 7% for the intraretinal layers except the outer segment/ retinal pigment epithelium (RPE) junction. There is no significant difference between scans acquired by different observers or during different visits. The ICCs obtained for the intraobserver and intervisit variability tests are greater than 0.75 for the total retina and all intraretinal layers, except the inner nuclear layer intraobserver and interobserver test and the outer plexiform layer, intraobserver, interobserver, and intervisit test. Our results indicate that thickness measurements for the total retina and all intraretinal layers (except the outer segment/RPE junction) performed using OCTRIMA are highly repeatable and reproducible.
The development of improved segmentation algorithms for more consistently accurate detection of retinal boundaries is a potentially useful solution to the limitations of existing optical coherence tomography (OCT) software. We modeled artifacts related to operator errors that may normally occur during OCT imaging and evaluated their influence on segmentation results using a novel segmentation algorithm. These artifacts included: defocusing, depolarization, decentration, and a combination of defocusing and depolarization. Mean relative reflectance and average thickness of the automatically extracted intraretinal layers was then measured. Our results show that defocusing and depolarization errors together have the greatest altering effect on all measurements and on segmentation accuracy. A marked decrease in mean relative reflectance and average thickness was observed due to depolarization artifact in all intraretinal layers, while defocus resulted in a less-marked decrease. Decentration resulted in a marked but not significant change in average thickness. Our study demonstrates that care must be taken for good-quality imaging when measurements of intraretinal layers using the novel algorithm are planned in future studies. An awareness of these pitfalls and their possible solutions is crucial for obtaining a better quantitative analysis of clinically relevant features of retinal pathology.
A 2-D finite element model of the cornea is developed to simulate corneal reshaping and the resulting deformation induced by refractive surgery. In the numerical simulations, linear and nonlinear elastic models are applied when stiffness inhomogeneities varying with depth are considered. Multiple simulations are created that employ different geometric configurations for the removal of the corneal tissue. Side-by-side comparisons of the different constitutive laws are also performed. To facilitate the comparison, the material property constants are identified from the same experimental data, which are obtained from mechanical tests on corneal strips and membrane inflation experiments. We then validate the resulting models by comparing computed refractive power changes with clinical results. Tissue deformations created by simulated corneal tissue removal using finite elements are consistent with clinically observed postsurgical results. The model developed provides a much more predictable refractive outcome when the stiffness inhomogeneities of the cornea and nonlinearities of the deformations are included in the simulations. Finite element analysis is a useful tool for modeling surgical effects on the cornea and developing a better understanding of the biomechanics of the cornea. The creation of patient-specific simulations would allow surgical outcomes to be predicted based on individualized finite element models.
We evaluate the ability of a nonlinear anisotropic diffusion process to enhance the contrast for structural boundary regions and to reduce the speckle noise in optical coherence tomography (OCT) images. We also investigate the suitability of various image features, such as gradient magnitude and intensity or gradient profiles, for boundary localization. The results suggest that the nonlinear anisotropic diffusion method has potential in assisting segmentation and quantification of fluid-filled regions in clinical OCT images.
A finite element method was used to study the biomechanical behavior of the cornea and its response to refractive surgery when stiffness inhomogeneities varying with depth are considered.
Side-by-side comparisons of different constitutive laws that have been commonly used to model refractive surgery were also performed. To facilitate the comparison, the material property constants were identified from the same experimental data, which were obtained from mechanical tests on corneal strips and membrane inflation experiments. We then validated the resulting model by comparing computed refractive power changes with clinical results.
The model developed provides a much more predictable refractive outcome when the stiffness inhomogeneities of the cornea and nonlinearities of the deformations are included in the finite element simulations. Thus, it can be stated that the inhomogeneous model is a more accurate representation of the corneal material properties in order to model the biomechanical effects of refractive surgery. The simulations also revealed that the para-central and peripheral parts of the cornea deformed less in response to pressure loading compared to the central cornea and the limbus. Furthermore, the deformations in response to pressure loading predicted by the non-homogeneous and nonlinear model, showed that the para-central region is mechanically enhanced in the meridional direction. This result is in agreement with the experimentally documented regional differences reported in the literature by other investigators.
We evaluated the efficacy, safety, and stability of femtosecond laser intrastromal refractive procedures in ex vivo and in vivo models. When compared with longer pulsewidth nanosecond or picosecond laser pulses, femtosecond laser-tissue interactions are characterized by significantly smaller and more deterministic photodisruptive energy thresholds, as well as reduced shock waves and smaller cavitation bubbles. We utilized a highly reliable, all-solid-state femtosecond laser system for all studies to demonstrate clinical practicality. Contiguous tissue effects were achieved by scanning a 5 μm focused laser spot below the corneal surface at pulse energies of approximately 2 - 4 microjoules. A variety of scanning patterns was used to perform three prototype procedures in animal eyes; corneal flap cutting, keratomileusis, and intrastromal vision correction. Superior dissection and surface quality results were obtained for lamellar procedures (corneal flap cutting and keratomileusis). Preliminary in vivo evaluation of intrastromal vision correction in a rabbit model revealed consistent and stable pachymetry changes, without significant inflammation or loss of corneal transparency. We conclude that femtosecond laser technology may be able to perform a variety of corneal refractive procedures with high precision, offering advantages over current mechanical and laser devices and techniques.
We investigated three potential femtosecond laser ophthalmic procedures: intrastromal refractive surgery, transcleral photodisruptive glaucoma surgery and photodisruptive ultrasonic lens surgery. A highly reliable, all-solid-state system was used to investigate tissue effects and demonstrate clinical practicality. Compared with longer duration pulses, femtosecond laser-tissue interactions are characterized by smaller and more deterministic photodisruptive energy thresholds, smaller shock wave and cavitation bubble sizes. Scanning a 5 (mu) spot below the target tissue surface produced contiguous tissue effects. Various scanning patterns were used to evaluate the efficacy, safety, and stability of three intrastromal refractive procedures in animal eyes: corneal flap cutting, keratomileusis, and intrastromal vision correction (IVC). Superior dissection and surface quality results were obtained for the lamellar procedures. IVC in rabbits revealed consistent, stable pachymetric changes, without significant inflammation or corneal transparency degradation. Transcleral photodisruption was evaluated as a noninvasive method for creating partial thickness scleral channels to reduce elevated intraocular pressure associated with glaucoma. Photodisruption at the internal scleral surface was demonstrated by focusing through tissue in vitro without collateral damage. Femtosecond photodisruptions nucleated ultrasonically driven cavitation to demonstrate non-invasive destruction of in vitro lens tissue. We conclude that femtosecond lasers may enable practical novel ophthalmic procedures, offering advantages over current techniques.
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