Search

Purpose In diabetic subjects, early visual functional alterations such as color vision deficiencies (CVDs) are known to precede clinically apparent diabetic retinopathy. Prominent photoreceptor outer segment degeneration and an increase in the number of retinal dual cones (co-expressing S- and M-opsins simultaneously) have been described in diabetic rat models, suggesting a connection with the development of CVDs. As cone opsin expression is controlled by thyroid hormones, we investigated the diabetic retina in association with thyroid hormone alterations. Methods In rat models of type 1 and 2 diabetes, dual cones were labeled by immunohistochemistry, and their numbers were analyzed in relation to free triiodothyronine (fT3) and free thyroxine (fT4) levels. Quantification of dual cones was also performed in human postmortem retinas. Additionally, a cross-sectional case-control study was performed where thyroid hormone levels were measured and color vision was assessed with Lanthony desaturated D15 discs. Results A higher number of dual cones was detectable in diabetic rats, correlating with fT4 levels. Dual cones were also present in postmortem human retinas, with higher numbers in the three diabetic retinas. As expected, age was strongly associated with CVDs in human patients, and the presence of diabetes also increased the risk. However, the current study failed to detect any effect of thyroid hormones on the development of CVDs. Conclusions Our results point toward the involvement of thyroid homeostasis in the opsin expression changes in diabetic rats and human samples. The evaluation of the possible clinical consequences warrants further research.

Successful retinal layer segmentation allows quantitative studies of the retinal structures based on OCT images, which mainly refer to the layer thickness measurements and morphology analyses. The aim of this chapter is to summarize the diagnostic capability of OCT based quantitative analysis for various eye diseases and additional factors affecting morphological measurements.

In the ophthalmic research, the measurement of the retinal thickness is usually employed for characterizing the structural changes of the retinal tissue. However, changes in the fractal dimension (FD) may provide additional information regarding the structure of the retinal layers and their early damage in ocular diseases. In the present paper, we investigated the possibility of detecting changes in the structure of the cellular layers of the retina by applying a two-dimensional fractal analysis to optical coherence tomography (OCT) images. OCT images were obtained from diabetic patients without retinopathy (DM, n = 38 eyes) and with mild diabetic retinopathy (MDR, n = 43 eyes) as well as in healthy subjects (Controls, n = 74 eyes). The two-dimensional fractal dimension was calculated using the differentiate box counting methodology. We evaluated the usefulness of quantifying the fractal dimension of layered structures in the detection of retinal damage. Generalized estimating equations considering within-subject inter-eye relations were used to test for differences between the groups. An adjusted p-value of

Purpose To evaluate and compare thickness changes in the retinal layers in the macula with optical coherence tomography (OCT) segmentation software after femtosecond laser–assisted phacoemulsification (study group) and conventional phacoemulsification (control group). Setting Department of Ophthalmology, Semmelweis University, Budapest, Hungary. Design Case-control study. Methods Total retinal thickness of the macula was evaluated using Stratus OCT 4 to 8 weeks postoperatively. The OCT images were segmented using OCT retinal image analysis software. Regional thickness data in the central area, inner rings, and outer rings were obtained and absolute and relative thicknesses of the individual retinal layers in the 2 study groups compared. Relative thickness was calculated as the ratio of the retinal layer to the total retinal thickness. Results All surgeries were uneventful. Statistically significant differences were found in absolute outer nuclear layer thickness and relative outer nuclear layer thickness in the inner and outer macular rings between the 2 groups. After adjusting for effective phaco time in multivariate modeling, type of surgery showed a significantly lower relative outer nuclear layer ratio in the inner retinal ring (0.26 with 95% confidence interval [CI], 0.25-0.27 versus 0.28 with 95% CI, 0.27-0.29; P =.03) and in the outer retinal ring (0.27 with 95% CI, 0.25-0.28 versus 0.29 with 95% CI, 0.28-0.31; P =.02) in the study group. Conclusion After cataract surgery, macular edema was detectable mainly in the outer nuclear layer in both groups but was significantly less using the femtosecond laser platform. Financial Disclosure Dr. Nagy is a consultant to Alcon-LenSx Lasers, Inc. The University of Miami and Dr. Cabrera DeBuc hold a pending patent used in the study (U.S. patent 61/139,082) and have the potential for financial benefit from its future commercialization. Drs. Ecsedy, Kovacs, Takacs, Tatrai, and Somfai have no financial or proprietary interest in any material or method mentioned.

OCT is usually employed for the measurement of retinal thickness. However, coherent reflected light carries more information characterizing the optical properties of tissue. Therefore, optical property changes may provide further information regarding cellular layers and early damage in ocular diseases. We investigated the possibility of OCT in detecting changes in the optical backscattered signal from layered retinal structures. OCT images were obtained from diabetic patients without retinopathy (DM, n = 38 eyes) or mild diabetic retinopathy (MDR, n = 43 eyes) and normal healthy subjects (n = 74 eyes). The thickness and reflectivity of various layered structures were assessed using a custom-built algorithm. In addition, we evaluated the usefulness of quantifying the reflectivity of layered structures in the detection of retinal damage. Generalized estimating equations considering within-subject inter-eye relations were used to test for differences between the groups. A modified p value of

Over the past two decades a significant number of OCT segmentation approaches have been proposed in the literature. Each methodology has been conceived for and/or evaluated using specific datasets that do not reflect the complexities of the majority of widely available retinal features observed in clinical settings. In addition, there does not exist an appropriate OCT dataset with ground truth that reflects the realities of everyday retinal features observed in clinical settings. While the need for unbiased performance evaluation of automated segmentation algorithms is obvious, the validation process of segmentation algorithms have been usually performed by comparing with manual labelings from each study and there has been a lack of common ground truth. Therefore, a performance comparison of different algorithms using the same ground truth has never been performed. This paper reviews research-oriented tools for automated segmentation of the retinal tissue on OCT images. It also evaluates and compares the performance of these software tools with a common ground truth.

Artificial UV irradiation of murine skin is a frequently used method for testing photosensitivity, study carcinogenesis and photoprotective effects of different compounds. However, doses of UV radiation and mouse strains used in experiments vary greatly. The genetic background of mice may influence the photosensitivity as melanin content, pigmentation and hair cycle parameters are dissimilar. Doses of UV are often expressed in relation to the minimal erythema dose (MED) that was not necessarily determined for the given strain. We set out to standardize the method of measuring photosensitivity in three commonly used mouse strains, C57BL/6N, Balb/c and SKH-1. We found that MED may not be determined for some strains as erythema development in mice with diverse genotypes differs greatly. We measured the oedema response in vivo and ex vivo by using OCT. Given the strain-specific variability of erythema, we introduced Clinically Relevant Dose (CRD) as a new term to replace MED in experiments, to describe the lowest dose that triggers a perceptible skin reaction in mice. Not only the CRD but the proportion of erythema and oedema were different in strains examined. C57BL/6N mice display skin reactions at the lowest UVB dose, while SKH-1 hairless mice show changes, mostly oedema, after higher doses of UVB. The cellular composition and skin thickness were examined by histopathology. IL-1beta and IL-6 levels in skin correlated with the increasing doses of UVB. Despite the variations in the degree of erythema and oedema, no major differences in cytokine expressions were seen among various strains of mice.

Optical coherence tomography (OCT) was introduced in the beginning of the 1990s as a new imaging tool that enables the high-resolution in vivo examination of biological tissues. It was first used in ophthalmology where the OCT technology revolutionized the diagnostics of the conditions of the macula and the vitreo-retinal interface. Today, there is intensive research on the possible applications of OCT in other specialties, e.g., angiology, oncology, gastroenterology, dermatology, and dentistry. In the future, OCT may play an important role in the diagnosis and monitoring of neurodegenerative diseases, owing to the fact that the retina is such a unique place of the nervous system where nerve fibers without myelin sheath forming direct synapses with the central nervous system can be found. These nerve fibers come from the ganglion cells of the retina, leave the eyeball through the lamina cribrosa, and then run towards the lateral geniculate body forming the optic nerve. According to recent studies, a pathological impairment of the retinal nerve fiber layer (RNFL) can be observed in numerous neurological conditions. Measuring the thickness of the nerve fiber layer with OCT may therefore be a reliable and accurate non-invasive method for the detection and monitoring of neurodegeneration, which, besides accurate diagnostics, may become an invaluable tool to assess the efficacy of neuroprotective substances.

Purpose The aim of this study was to evaluate the effect of axial length (AL) on the thickness of intraretinal layers in the macula using optical coherence tomography (OCT) image analysis. Methods Fifty three randomly selected eyes of 53 healthy subjects were recruited for this study. The median age of the participants was 29 years (range: 6 to 67 years). AL was measured for each eye using a Lenstar LS 900 device. OCT imaging of the macula was also performed by Stratus OCT. OCTRIMA software was used to process the raw OCT scans and to determine the weighted mean thickness of 6 intraretinal layers and the total retina. Partial correlation test was performed to assess the correlation between the AL and the thickness values. Results Total retinal thickness showed moderate negative correlation with AL (r = -0.378, p = 0.0007), while no correlation was observed between the thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCC), retinal pigment epithelium (RPE) and AL. Moderate negative correlation was observed also between the thickness of the ganglion cell layer and inner plexiform layer complex (GCL+IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL) and AL which were more pronounced in the peripheral ring (r = -0.402, p = 0.004; r = -0.429, p = 0.002; r = -0.360, p = 0.01; r = -0.448, p = 0.001). Conclusions Our results have shown that the thickness of the nuclear layers and the total retina is correlated with AL. The reason underlying this could be the lateral stretching capability of these layers; however, further research is warranted to prove this theory. Our results suggest that the effect of AL on retinal layers should be taken into account in future studies.

Background: To investigate the influence of scan distance on retinal boundary detection errors (RBDEs) and retinal thickness measurements by spectral domain optical coherence tomography (SD-OCT). Methods: 10 eyes of healthy subjects, 10 eyes with diabetic macular edema (DME) and 10 eyes with neovascular age-related macular degeneration (AMD) were examined with RTVue SD-OCT. The MM5 protocol was used in two consecutive sessions to scan the macula. For the first session, the device was set 3.5 cm from the eye in order to obtain detectable signal with low fundus image quality (suboptimal setting) while in the second session a distance of 2.5 cm was set with a good quality fundus image. The signal strength (SSI) value was recorded. The score for retinal boundary detection errors (RBDE) was calculated for ten scans of each examination. RBDE scores were recorded for the whole scan and also for the peripheral 1.0 mm region. RBDE scores, regional retinal thickness values and SSI values between the two sessions were compared. The correlation between SSI and the number of RBDEs was also examined. Results: The SSI was significantly lower with suboptimal settings compared to optimal settings (63.9±12.0 vs. 68.3±12.2, respectively, p = 0.001) and the number of RBDEs was significantly higher with suboptimal settings in the “all-eyes” group along with the group of healthy subjects and eyes with DME (9.1±6.5 vs. 6.8±6.3, p = 0.007; 4.4±2.6 vs. 2.5±1.6, p = 0.035 and 9.7±3.3 vs. 5.1±3.7, p = 0.008, respectively). For these groups, significant negative correlation was found between the SSI and the number of RBDEs. In the AMD group, the number of RBDEs was markedly higher compared to the other groups and there was no difference in RBDEs between optimal and suboptimal settings with the errors being independent of the SSI. There were significantly less peripheral RBDEs with optimal settings in the “all-eyes” group and the DME subgroup (2.7±2.6 vs. 4.2±2.8, p = 0.001 and 1.4±1.7 vs. 4.1±2.2, p = 0.007, respectively). Retinal thickness in the two settings was significantly different only in the outer-superior region in DME. Conclusions: Optimal distance settings improve SD-OCT SSI with a decrease in RBDEs while retinal thickness measurements are independent of scanning distance.

Purpose Differences in optical and irregularity measures of abnormal retinal tissue may provide additional information of impairment of the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer complex (GCL+IPL) in multiple sclerosis (MS). The purpose of our study was to estimate these retinal changes in MS. Methods Twenty-seven patients with MS were examined using Stratus OCT. The raw macular OCT data was exported and processed using OCTRIMA software and the fractal dimension (FD) and layer index (LI) values of seven intraretinal layers were obtained. The enrolled eyes were divided into two groups, based on ON in the history (ON+ group, n=13 and ON- group, n=14). Data of 73 healthy subjects (N) were used as controls. ANOVA with Newman-Keuls post-hoc analysis was used for the comparison of FD and LI values. The level of significance was set at p

Background The sensitivity of Optical Coherence Tomography (OCT) images to identify retinal tissue morphology characterized by early neural loss from normal healthy eyes is tested by calculating structural information and fractal dimension. OCT data from 74 healthy eyes and 43 eyes with type 1 diabetes mellitus with mild diabetic retinopathy (MDR) on biomicroscopy was analyzed using a custom-built algorithm (OCTRIMA) to measure locally the intraretinal layer thickness. A power spectrum method was used to calculate the fractal dimension in intraretinal regions of interest identified in the images. ANOVA followed by Newman-Keuls post-hoc analyses were used to test for differences between pathological and normal groups. A modified p value of Results Fractal dimension was higher for all the layers (except the GCL + IPL and INL) in MDR eyes compared to normal healthy eyes. When comparing MDR with normal healthy eyes, the highest AUROC values estimated for the fractal dimension were observed for GCL + IPL and INL. The maximum discrimination value for fractal dimension of 0.96 (standard error =0.025) for the GCL + IPL complex was obtained at a FD ≤ 1.66 (cut off point, asymptotic 95% Confidence Interval: lower-upper bound = 0.905-1.002). Moreover, the highest AUROC values estimated for the thickness measurements were observed for the OPL, GCL + IPL and OS. Particularly, when comparing MDR eyes with control healthy eyes, we found that the fractal dimension of the GCL + IPL complex was significantly better at diagnosing early DR, compared to the standard thickness measurement. Conclusions Our results suggest that the GCL + IPL complex, OPL and OS are more susceptible to initial damage when comparing MDR with control healthy eyes. Fractal analysis provided a better sensitivity, offering a potential diagnostic predictor for detecting early neurodegeneration in the retina.

Background: To identify local structural and optical derangement in the neural retina of individuals with type 1 diabetes having early diabetic retinopathy (DR) and compare with healthy non-diabetic controls and type 1 diabetic individuals having no DR. Methods: Optical coherence tomography (TDOCT) examination was performed on a total of 74 healthy eyes, 38 eyes with type 1 diabetes mellitus (DM) with no retinopathy and 43 eyes with mild DR (MDR). A total of 6 intraretinal layers were segmented on OCT images. Thickness and reflectance-based measurements were extracted for each OCT scan using features measured locally for each intraretinal layer. Results: In the analysis where local measures were averaged in the separated macular regions outside the foveola, the mean thickness values of the outer segment of photoreceptors (OS) in the perifoveal region, ganglion cell and inner plexiform layer (GCL+IPL) complex in the parafoveal and outer plexiform layer (OPL) in the foveal region were significantly smaller (13%, 8% and 36%; respectively, p

To assess the structure and function of the macula in advanced retinitis pigmentosa (RP).Twenty-nine eyes of 22 patients with RP were compared against 17 control eyes. Time-domain optical coherence tomography (OCT) data were processed using OCTRIMA (optical coherence tomography retinal image analysis) as a means of quantifying commercial OCT system images. The thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer complex (GCL+IPL), inner nuclear layer and outer plexiform layer complex (INL+OPL), and the outer nuclear layer (ONL) were measured. Multifocal electroretinography (mfERG) was performed; two groups were formed based on the mfERG findings. Fourteen eyes had no detectable central retinal function (NCRF) on mfERG; detectable but abnormal retinal function (DRF) was present in the mfERG of the other 15 eyes.The thickness of the ONL in the central macular region was significantly less in the NCRF eyes compared with that in both DRF eyes and controls. The ONL was significantly thinner in the pericentral region in both patient groups compared with that in controls, whereas the thickness of the GCL+IPL and INL+OPL was significantly decreased only in the NCRF eyes. The RNFL in the peripheral region was significantly thicker, whereas the thickness of the GCL+IPL and ONL was significantly thinner in both patient groups compared with that in controls.The results are consistent with degeneration of the outer retina preceding inner retinal changes in RP. OCT image segmentation enables objective evaluation of retinal structural changes in RP, with potential use in the planning of therapeutic interventions and conceivably as an outcome measure.

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.

Neuromyelitis optica (NMO, Devic-syndrome) is a rare, relapsing autoimmune disease of the central nervous system, which is distinguished from other demyelinating disorders by a recently identified, specific autoantibody. By demonstrating the anti-aquaporin-4 IgG in the serum, a heterogenous group of syndromes can be defined, called NMO-spectrum. In the future, optical coherence tomography may support this diagnosis besides the clinical features, imaging examinations and presence of serum antibody. Early recognition and treatment can improve clinical outcome even in serious condition. Long-term immunosuppressive therapy is advised to prevent further relapses and to stabilize or improve clinical status. Hereby, we report a case of a 51-year-old woman, under treatment for one and a half years. We summarize the current knowledge about the pathomechanism, diagnostic strategy and therapy of neuromyelitis optica. We review recent findings and the diagnostic value of a new, non-invasive ophtalmological examination, the optical coherence tomography. According to the first results, this method may be helpful in the early differential diagnosis of optic neuritis.

Purpose Stratus OCT enables fast and normal scanning of the macula. It is unknown whether there are any differences between the measured values by these two protocols, therefore our purpose was to compare the central subfield mean thickness (CSMT), center point thickness (CPT) and total macular volume (TMV) measured by the fast and the normal protocols of Stratus OCT. Methods Twenty-two eyes of 22 diabetic patients were recruited in this study. The inclusion criteria were diffuse diabetic macular edema on the fundus and CSMT more than 250 µm measured by the OCT fast protocol. Each eye was scanned by both types of OCT scanning protocols. CSMT, CPT and TMV values were recorded. The thickness values measured by the two types of protocols were compared using paired Student t-test. The level of significance was set at 0.05. Results No significant difference was found between any of the parameters measured by the two OCT protocols. The mean difference (MD) between CSMT and CPT measured by fast and normal protocols were 0.77 ± 10.50 µm (range, 1-29 µm; p=0.73) and 1.36 ± 21.55 µm (range, 0-52 µm; p=0.77) which were 0.24% and 0.45% of the mean thickness, respectively. In case of TMV, the MD was 0.01 ± 0.12 mm3 (range, 0-0.29 mm3; p=0.68) which was 0.12% of the mean TMV. Conclusion However, no significant difference was found between the thickness measurements, care must be taken when comparing CSMT and CPT values between the fast and normal protocols in eyes with diffuse diabetic macular edema because inner retinal boundary detection errors can be present at the cystoid cavities influencing the thickness measurements.

We determine the reliability and reproducibility of retinal thickness measurements with a custom-built OCT retinal image analy- sis software OCTRIMA. Ten eyes of five healthy subjects undergo repeated standard macular thickness map scan sessions by two expe- rienced examiners using a Stratus OCT device. Automatic/semi auto- matic 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/ reti- nal pigment epithelium RPE junction. There is no significant differ- ence 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 junc- tion performed using OCTRIMA are highly repeatable and reproducible. © 2009 Society of Photo-Optical Instrumentation Engineers. DOI: 10.1117/1.3268773

Purpose: Optical coherence tomography (OCT) enables high resolution, cross-sectional imaging of the retina. The various retinal layers can be distinguished on OCT images using an algorithm of our own design. In the present study we aimed to assess the intraobserver variability of the segmentation algorithm. Methods: Ten eyes of five healthy subjects were involved in the study (mean age 29 years). Standard macular mapping was performed using a Stratus OCT™ device. All OCT images were segmented using an algorithm of our own design, average thickness and volume data were obtained for the following cellular layers: retinal nerve fiber layer (RNFL), ganglion cell layer and internal plexiform layer complex (GCL+IPL), inner nuclear layer (INL), outer plexiform layer (OPL) and outer nuclear layer (ONL). A manual correction tool was developed to overwrite the automatic segmentation in particular cases where the algorithm failed. The segmentation of the same OCT scans was repeated after one week, and the Coefficient of Repeatability (CR) was calculated in order to assess the accuracy of all measurements. Results: The CR results for the thickness of the various cellular layers of the retina (in the order as they appeared above) were as follows: 0.47μm, 1.47μm, 0.50μm, 0.57μm, and 0.26μm. Similarly, the CR for the volumetric measurements were 0.054mm3, 0.057mm3, 0.017mm3, 0.015mm3, 0.014mm3, 0.025mm3, respectively. Conclusions: The volumetric and thickness results for the various cellular layers of the retina obtained with our custom segmentation algorithm are highly reproducible. According to our results the measurement accuracy of our algorithm is below the resolution of the Stratus OCT device.

The sensitivity of OCT images to sample diabetic morphology is tested by calculating attenuation coefficients and fractal dimension. Fractal analysis provided a better sensitivity, offering a potential diagnostic predictor for detecting early diabetic retinopathy.