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Neural crest (NC) contributes to various structures of the eye including cornea, ciliary body and retina. The association of NC-derived cells with hyaloid vessels in the form of pericytes is established. Similarly, persistence of NC-derived cells in the inner retina layer of the mature retina has been suggested. To date, no specific function has been attributed to them. NC-derived Bone morphogenetic protein 7 (BMP7) controls neurogenic properties in the brain and regulates glia differentiation. Here, we assessed the role of NC-derived BMP7 in the adult retina.BMP7 expression was determined using Bmp7LacZ reporter mice. BMP7 was expressed in GCL, IPL, OPL, and photoreceptors in P0, P14 and P30 retinas. Lineage tracing confirmed the presence of NC-derived cells in the GCL, INL, and ONL. Some but not all cells associated with vasculature. To test the function of NC-derived Bmp7, Bmp7fl/flWnt1cre (Bmp7ncko) mice were assessed by histological and functional methods. Loss of NC-derived cells in the GCL and INL and mild structural abnormalities were observed in the Bmp7ncko retina. Electroretinography revealed reduced a wave under photopic conditions and b wave under both scotopic and photopic conditions. The neuronal circuitry in the inner retina appeared affected, evidenced by decreased Calbindin in the GCL, IPL and INL. In the outer retina, S-opsin was increased. BMP7 expression in the mutant retina was strongly decreased at birth, but increased expression from cells other than NC was observed in the adult retina. This was associated with an increase in IBA1, suggestive that loss of NC-derived BMP7 predisposes to development of gliosis-like changes in the adult retina. Overall, our data reveal an important contribution of NC-derived BMP7 for the development and function of the inner and outer retina.

To compare thickness and reflectance of retinal layer findings in patients with idiopathic epiretinal membranes (ERMs) before and after surgery with those of normal controls.Retrospective study.Patients with ERMs before and after surgery and healthy controls.Spectral-domain (SD) OCT imaging of eyes with ERMs before and after surgery and of healthy eyes were analyzed for morphologic appearance and using a customized algorithm to measure retinal layer reflectance and thickness. Findings were correlated with visual acuity outcomes.Retinal layer thickness and reflectance.Thirty-four ERM and 12 healthy eyes were identified. Mean preoperative best-corrected visual acuity (BCVA) improved from 0.53±0.31 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/68) to 0.41±0.25 logMAR (Snellen equivalent, 20/51) after surgery (P = 0.030). Differences in reflectance and thickness of retinal layers were identified among the preoperative ERM, postoperative ERM, and healthy eyes. High preoperative reflectance of the internal limiting membrane (ILM) to outer plexiform layer (OPL) was correlated with better postoperative BCVA (r = -0.451; P = 0.007). A larger improvement in BCVA was correlated with preoperative thick measurements of the outer nuclear layer (r = 0.514; P = 0.002), high reflectance of the group of layers from the ILM to the OPL (r = 0.426; P = 0.012), and low reflectance of the photoreceptor layer (r = -0.453; P = 0.007). Using linear regression analysis, better postoperative BCVA was associated with better preoperative vision (standardized regression coefficient, 0.553; P = 0.001) and high reflectance of the group of layers from the ILM to OPL (standardized regression coefficient, -0.526; P = 0.001). A larger improvement in BCVA was associated with worse preoperative BCVA (standardized regression coefficient, -0.539; P0.001) and high reflectance of the group of layers from the ILM to OPL (standardized regression coefficient, -0.428; P = 0.001).Quantitative differences in reflectance and thickness among preoperative, postoperative, and normal SD OCT imaging allow assessment of retina layer changes secondary to ERMs. High reflectance of the ILM to OPL correlated with and was associated with better postoperative BCVA and improvement in BCVA.

Background We investigated structural injury patterns in the peripapillary retinal nerve fibre layer (p-RNFL) and ganglion cell inner plexiform layer (GCIPL) caused by ethambutol treatment. Methods Sixty-four patients undergoing ethambutol treatment at Zhejiang Chinese Medicine and Western Medicine Integrated Hospital were recruited. Fourteen (14) exhibited visual dysfunction (abnormal group), and the remaining 50 had no visual dysfunction (subclinical group). The thickness of the p-RNFL, total macular retina layer and GCIPL were measured using Cirrus-HD Optical coherence tomography (Cirrus-HD OCT, Cirrus high-definition optical coherence tomography), and compared with 60 healthy, age-matched controls. Results The p-RNFL thickness was similar in both subclinical and control groups. When compared with the control group, p-RNFL thickness in the abnormal group was significantly increased in the inferior and superior quadrants (GEE, P = 0.040, P = 0.010 respectively). In contrast with the subclinical group, p-RNFL thickness in the inferior quadrant was increased in the abnormal group (GEE, P = 0.047). The GCIPL thickness in the inferonasal and inferior sectors was significantly deceased in the subclinical group when compared with controls (GEE, P = 0.028, P = 0.047, respectively). The average and minimum value of GCIPL thickness, and thickness in the superonasal, inferior, inferotemporal, superotemporal and superior sectors were significantly decreased in the abnormal group when compared with controls (GEE, P = 0.016, P = 0.001, P = 0.028, P = 0.010, P = 0.012, P = 0.015, P = 0.010, respectively). The cube average macular thickness (CAMT) in the abnormal group was significantly thinner than controls (GEE, P = 0.027). Conclusions GCIPL measurements using Cirrus-HD OCT detected retinal ganglion cell layer loss following ethambutol treatment, before visual dysfunction occurred.

Purposeto evaluate and correlate the alterations of microvascular and chorioretinal structure in Type 2 diabetes mellitus (T2DM) patients without clinical signs of DR.MethodsT2DM patients were randomized sampled from Guangzhou Diabetic Eye Study and healthy controls from the community of Guangzhou, China were recruited in this cross-sectional study. Demographic, clinical and ocular parameters were regularly obtained. Retinal thickness (RT), retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness, outer retina layer (ORL) thickness and choroid thickness (CT) were automatically evaluated by swept-source optical coherence tomography (SS-OCT) in the 1, 3, and 6 mm centered on fovea. Vessel density (VD) was obtained by OCT angiography (OCTA) in the 1 and 3 mm centered on the fovea.Results1,444 eyes of 1,444 individuals (722 T2DM patients and 722 healthy controls) were included in the final analyses. Macular average RNFL was thinned (P < 0.001), average GC-IPL was thickened (P < 0.001), and ORL was thickened (P = 0.012) in DM patients compared with healthy controls independent of confounding factors. VD was significantly increased in diabetic patients without DR. Correlations were found between VD and specific layers of retina both in DM patients and in healthy controls. Especially in DM patients, average RT in positively related with parafoveal VD (β= 0.010, 95%CI: 0.003 to 0.017) and total average VD (β= 0.010,95%CI: 0.003 to 0.016). Specifically, RNFL thickness is inversely related with VD, while both GC-IPL and ORL thickness are positively related with VD in diabetic patients without DR.ConclusionThis study reports and correlates the early alterations of chorioretinal structure and retinal superficial vessels in T2DM patients even before the onset of clinical signs of DR. Findings of this study may provide novel insights to explore the pathogenesis of DR.

Purpose The purpose of this study was to test the hypothesis that anti-oxidant and / or anti-inflammation drugs that suppress rod death in cyclic light-reared Pde6brd10 mice are also effective in dark-reared Pde6brd10 mice. Methods In untreated dark-reared Pde6brd10 mice at post-natal (P) days 23 to 24, we measured the outer nuclear layer (ONL) thickness (histology) and dark-light thickness difference in external limiting membrane-retinal pigment epithelium (ELM-RPE) (optical coherence tomography [OCT]), retina layer oxidative stress (QUEnch-assiSTed [QUEST] magnetic resonance imaging [MRI]); and microglia/macrophage-driven inflammation (immunohistology). In dark-reared P50 Pde6brd10 mice, ONL thickness was measured (OCT) in groups given normal chow or chow admixed with methylene blue (MB) + Norgestrel (anti-oxidant, anti-inflammatory), or MB or Norgestrel separately. Results P24 Pde6brd10 mice showed no significant dark-light ELM-RPE response in superior and inferior retina consistent with high cGMP levels. Norgestrel did not significantly suppress the oxidative stress of Pde6brd10 mice that is only found in superior central outer retina of males at P23. Overt rod degeneration with microglia/macrophage activation was observed but only in the far peripheral superior retina in male and female P23 Pde6brd10 mice. Significant rod protection was measured in female P50 Pde6brd10 mice given 5 mg/kg/day MB + Norgestrel diet; no significant benefit was seen with MB chow or Norgestrel chow alone, nor in similarly treated male mice. Conclusions In early rod degeneration in dark-reared Pde6brd10 mice, little evidence is found in central retina for spatial associations among biomarkers of the PDE6B mutation, oxidative stress, and rod death; neuroprotection at P50 was limited to a combination of anti-oxidant/anti-inflammation treatment in a sex-specific manner.

To develop an automated retina layer thickness measurement tool for the ImageJ platform, to quantitate nuclear layers following the retina contour. We developed the ThicknessTool (TT), an automated thickness measurement plugin for the ImageJ platform. To calibrate TT, we created a calibration dataset of mock binary skeletonized mask images with increasing thickness masks and different rotations. Following, we created a training dataset and performed an agreement analysis of thickness measurements between TT and two masked manual observers. Finally, we tested the performance of TT measurements in a validation dataset of retinal detachment images. In the calibration dataset, there were no differences in layer thickness between measured and known thickness masks, with an overall coefficient of variation of 0.00%. Training dataset measurements of immunofluorescence retina nuclear layers disclosed no significant differences between TT and any observer’s average outer nuclear layer (ONL) (p = 0.998), inner nuclear layer (INL) (p = 0.807), and ONL/INL ratio (p = 0.944) measurements. Agreement analysis showed that bias between TT vs. observers’ mean was lower than between any observers’ mean against each other in the ONL (0.77 ± 0.34 µm vs 3.25 ± 0.33 µm) and INL (1.59 ± 0.28 µm vs 2.82 ± 0.36 µm). Validation dataset showed that TT can detect significant and true ONL thinning (p = 0.006), more sensitive than manual measurement capabilities (p = 0.069). ThicknessTool can measure retina nuclear layers thickness in a fast, accurate, and precise manner with multi-platform capabilities. In addition, the TT can be customized to user preferences and is freely available to download.

To identify common optical coherence tomography (OCT) characteristics of taxane-related CME (T-CME) to differentiate it from CME associated with other causes (O-CME) and to present multimodal imaging findings of T-CME. To differentiate T-CME from O-CME, pooled SD-OCT images from 14 previous publications and images obtained from our multicenter case series of 3 patients with multimodal imaging of T-CME were compared with 16 consecutive cases of O-CME. Images were graded by 2 masked retinal specialists based on the presence of pre-specified OCT characteristics such as CME centered around fovea, outer retinal cysts more prominent compared with inner retinal cysts, continuous outer plexiform layer (OPL) and inner plexiform layer (IPL), intact outer retina layer, attenuation of outer retina layers by overlying retinal layers, and the presence of subretinal fluid. Comparing 19 and 16 SD-OCT images of T-CME and O-CME, respectively, T-CME showed a significantly higher rate of the continuous OPL and IPL layer and a higher composite score of the various pre-specified OCT features. All other individual features showed no significant difference between T-CME and O-CME. All our patients had T-CME that had vague petalloid patterns on the late-stage FFA, with late leakage on ICGA. OCT angiography in one case showed an intact foveal avascular zone. T-CME is a rare but important complication of taxane chemotherapy. Specific OCT features such as an intact continuous OPL and IPL layer combined with other OCT features can help distinguish T-CME from O-CME, and early diagnosis is clinically important as cessation of taxanes before the retinal layers are disrupted may prevent permanent vision loss.

BackgroundTo evaluate retinal thickness profiles in eyes with and without diabetic retinopathy (DR) using spectral-domain optical coherence tomography (SD-OCT) among individuals with diabetes.MethodsParticipants were recruited from the Singapore Epidemiology of Eye Diseases Study, a population-based study among Chinese, Malays and Indians aged 40 years or older residing in Singapore. All participants underwent standardised systemic and ophthalmic examinations. Average thickness of the macula, ganglion cell-inner plexiform layer and outer retina layer (from the outer plexiform layer to the retinal pigment epithelium layer) were measured using SD-OCT. DR status and severity were graded based on fundus photographs using the modified Airlie House classification system. Participants with macular oedema were excluded.Results2240 eyes from 1280 participants were included. Of these, 1764 (78.7%) eyes had no DR, 351 (15.7%) eyes had minimal or mild DR and 125 (5.6%) eyes had moderate or worse DR. After adjusting for age, gender, ethnicity, axial length, hypertension, glycated haemoglobin, body mass index, total cholesterol and diabetes duration, eyes with DR had thicker macula (245.44 µm vs 243.04 µm, P=0.03) and outer retina (124.26 µm vs 123.08 µm, P=0.01) than eyes without DR. When stratified by DR severity, thicker macula (250.24 µm vs 242.88 µm, P=0.011) and outer retina (126.4 µm vs 123.0 μm, P=0.006) were observed in eyes with moderate or worse, but not minimal or mild DR, compared with eyes without DR.ConclusionsEven in the absence of macular oedema, eyes with DR, particularly those with more severe DR, had thicker macular and outer retinal layers than eyes without DR.

Significance: Selective retina therapy (SRT) selectively targets the retinal pigment epithelium (RPE) and reduces negative side effects by avoiding thermal damages of the adjacent photoreceptors, the neural retina, and the choroid. However, the selection of proper laser energy for the SRT is challenging because of ophthalmoscopically invisible lesions in the RPE and different melanin concentrations among patients or even regions within an eye. Aim: We propose and demonstrate SRT monitoring based on speckle variance optical coherence tomography (svOCT) for dosimetry control. Approach: M-scans, time-resolved sequence of A-scans, of ex vivo bovine retina irradiated by 1.7-μs duration laser pulses were obtained by a swept-source OCT. SvOCT images were calculated as interframe intensity variance of the sequence. Spatial and temporal temperature distributions in the retina were numerically calculated in a 2-D retinal model using COMSOL Multiphysics. Microscopic images of treated spots were obtained before and after removing the upper neural retinal layer to assess the damage in both RPE and neural layers. Results: SvOCT images show abrupt speckle variance changes when the retina is irradiated by laser pulses. The svOCT intensities averaged in RPE and photoreceptor layers along the axial direction show sharp peaks corresponding to each laser pulse, and the peak values were proportional to the laser pulse energy. The calculated temperatures in the neural retina layer and RPE were linearly fitted to the svOCT peak values, and the temperature of each lesion was estimated based on the fitting. The estimated temperatures matched well with previously reported results. Conclusion: We found a reliable correlation between the svOCT peak values and the degree of retinal lesion formation, which can be used for selecting proper laser energy during SRT.

C244 Aided Diagnosis (CAD) using Artificial Intelligence (AI) techniques is being widely used these days especially in the field of medical imaging. Central Serous Chorioretinopathy (CSCR) is a common visual impairment syndrome that is predominately found amongst the young age fellows. Its main reason is the abnormal accumulation of serous in macula which is the central region of retina layer. Optical Coherence Tomography (OCT) is a non-invasive mean of eye inspection that helps in the early diagnosis of retina related diseases more efficiently than traditional methods. In this paper we report a CAD based fully automated algorithm for the detection of CSCR affected subjects using k-NN classifier. We extracted three discrete features based on the thickness of the retina layer and area of serous deposits. We have studied 80 retinal subjects (40 healthy and 40 CSCR affected OCT scans) during our research and accurately classified all the test cases for a value of k = 5, achieving 100% efficiency.

To understand the pathogenesis of ophthalmic disease, utilizing small animal models such as mouse is necessary because of their ease of maintenance and availability. For identifying pathophysiology and drug development of retinal diseases in mouse model, optical coherence tomography angiography (OCTA) is promising imaging modality visualizing not only microstructure but also microvasculature. In this study, we serially imaged 3D structure and angiography of laser-induced choroidal neovascularization (CNV) in the mouse retina with/without anti-VEGF treatment. Also, the volume changes of CNV and avascular region in choroid layer are measured for identifying effects of anti-VEGF. A lab-built high-speed OCTA prototype using the wavelength-swept laser centered at 1040 nm with 230 kHz A-scan rate acquired 3-D volumetric data consisted of 1024 x 1024 x 3 A-scans. The OCTA scanned 1.7 mm x 1.7 mm area around ONH. For obtaining angiography, amplitude decorrelation from 3 consecutive B-scans at each position was generated. Seven days after the laser photocoagulation at mouse retina for generation of the laser-induced CNV, intravitreal administration of Fc and VEGF-Trap was given in the therapeutic arm. The OCTA were performed at 6, 14, 21 and 35 days after laser photocoagulation. Vasculatures of inner retina, outer retina and choroid layers were separately visualized after RPE flattening and layer segmentation. To investigate therapeutic effects of anti-VEGF treatment, the relative area and volume of CNV in outer retina layer is measured. Also, total volume of avascular zone surrounding the laser injury site in choroid layer is also analyzed.

The intravitreal injection of N-methyl-d-aspartate (NMDA), a glutamate analogue, is an established model for fast retinal ganglion cell (RGC) degeneration. Yet, NMDA does not cause specific RGC damage. Now, the effects on the whole retina were analyzed. Additionally, the related effects for the structure and apoptotic levels of the optic nerve were investigated. Therefore, different NMDA concentrations were intravitreally injected in rats (20, 40, or 80 nmol NMDA or PBS). At days 3 and 14, Brn-3a+ RGCs were degenerated. A damage of calretinin+ amacrine cells was also recognized at day 14. Only a slight damage was observed in regard to PKCα+ bipolar cells, while rhodopsin+ photoreceptors remained intact. A long-lasting retinal microglia response was observed from day 3 up to day 14. Furthermore, a partial degeneration of the optic nerve was noted. At day 3, the SMI-32+ neurofilaments were just slightly affected, whereas the neurofilament structure was further degenerated at day 14. However, the luxol fast blue (LFB)-stained myelin structure remained intact from day 3 up to day 14. Interestingly, apoptotic mechanisms, like FasL and Fas co-localization as well as caspase 3 activation, were restricted to the optic nerve of the highest NMDA group at this late stage of degeneration. The degeneration of the optic nerve is probably only a side effect of neuronal degeneration of the inner retinal layers. The intact myelin structure might form a barrier against the direct influence of NMDA. In conclusion, this model is very suitable to test therapeutic agents, but it is important to analyze all inner retina layers and the optic nerve to determine their efficacy in this model more precisely.

Age-related macular degeneration (AMD) is an eye condition that is considered to be one of the leading causes of blindness among people over 50. Recent studies suggest that the mechanical properties in retina layers are affected during the early onset of disease. Therefore, it is necessary to identify such changes in the individual layers of the retina so as to provide useful information for disease diagnosis. In this study, we propose using an acoustic radiation force optical coherence elastography (ARF-OCE) system to dynamically excite the porcine retina and detect the vibrational displacement with phase resolved Doppler optical coherence tomography. Due to the vibrational mechanism of the tissue response, the image quality is compromised during elastogram acquisition. In order to properly analyze the images, all signals, including the trigger and control signals for excitation, as well as detection and scanning signals, are synchronized within the OCE software and are kept consistent between frames, making it possible for easy phase unwrapping and elasticity analysis. In addition, a combination of segmentation algorithms is used to accommodate the compromised image quality. An automatic 3D segmentation method has been developed to isolate and measure the relative elasticity of every individual retinal layer. Two different segmentation schemes based on random walker and dynamic programming are implemented. The algorithm has been validated using a 3D region of the porcine retina, where individual layers have been isolated and analyzed using statistical methods. The errors compared to manual segmentation will be calculated.

The Cngb1 locus-encoded β-subunit of rod cGMP-gated cation channel and associated glutamic acid rich proteins (GARPs) are required for phototransduction, disk morphogenesis, and rod structural integrity. To probe individual protein structure/function of the GARPs, we have characterized several transgenic mouse lines selectively restoring GARPs on a Cngb1 knockout (X1−/−) mouse background. Optical coherence tomography (OCT), light and transmission electron microscopy (TEM), and electroretinography (ERG) were used to analyze 6 genotypes including WT at three and ten weeks postnatal. Comparison of aligned histology/OCT images demonstrated that GARP2 accelerates the rate of degeneration. ERG results are consistent with the structural analyses showing the greatest attenuation of function when GARP2 is present. Even 100-fold or more overexpression of GARP1 could not accelerate degeneration as rapidly as GARP2, and when co-expressed GARP1 attenuated the structural and functional deficits elicited by GARP2. These results indicate that the GARPs are not fully interchangeable and thus, likely have separate and distinct functions in the photoreceptor. We also present a uniform murine OCT layer naming nomenclature system that is consistent with human retina layer designations to standardize murine OCT, which will facilitate data evaluation across different laboratories.

Human retina is different from other ocular tissues, such as cornea, crystalline lens and vitreous because of high scattering performance. As an anisotropic tissue, we cannot neglect its impact on the polarization state of the scattered light. In this paper, Mie scattering and radiative transfer theory are applied to analyze the polarization state of backscattered light from four types of retinal tissues, including neural retina, retinal pigment epithelial (RPE), choroid and sclera. The results show that the most backscattered zones in different depths have almost the same electrical fields of Jones vector, which represents the polarization state of light, whether neural retina layer is under normal incidence or oblique incidence. Very little change occurs in the polarization of backscattered light compared to that of the incident light. Polarization distribution of backward scattered light from neural retina layer doesn’t make apparent effects on polarization phase shifting in spectral domain OCT because its thickness is far less than photon mean free path, while other retinal tissues do not meet this rule.

The retinal pigment epithelium (RPE) is a monolayer to function as a compact barrier between photoreceptor and choroid and also a regulator of the overlying photoreceptor layer by providing nutrients. If RPE is damaged, choroidal neovascularization is occurred, accompanied by inflammation, which leads to degeneration of whole retina layer and furthermore, loss of vision. Thus, the preservation of RPE layer is very critical treatment to block the progression and occurrence of diverse ocular disease, inducing age-related macular degeneration (AMD). In this study, we explored the new role of SP in RPE regeneration. After confirming the expression of NK-1R on ARPE-19 cells, we treated SP to ARPE-19 cells in vitro to evaluate the effect of SP on proliferation rate and migratory capacity. SP could promote proliferation and migration of ARPE-19 in dose-dependent manner in vitro. Based on the in vitro data, 5nmole/kg of SP was intravitreally treated to laser-induced RPE damaged mice in vivo, showing that PBS-injected mice had severed disturbed retina layer, whereas SP-injected mice maintained retina layer more intact without detachment of RPE. In addition to histological comparison, the efficacy of SP was assessed according to the score that indicate the severity of retina degeneration. This confirmed that SP can exert the beneficial effect on laser-induced RPE damage. Collectively, our findings suggest that SP can stimulate the regeneration of RPE layer and thus, it may be possible that SP is used as the new therapeutics for RPE-damaged disease including AMD.

Purpose. To compare two different spectral-domain optical coherence tomography (OCT) systems in regard to full macular thickness (MT) and ganglion cell layer-inner plexiform layer (GCIPL) measures and in regard to structure-function correlation when compared to standard automated perimetry (SAP).Methods. Seventeen primary open angle glaucoma patients and 16 controls (one eye per subject) were enrolled. MT and GCIPL thicknesses were measured by Cirrus and Spectralis OCTs. Octopus Perimeter 101 (G2 protocol) reports sensitivity in mean defect (dB). Differences between measurements were assessed with Student’st-test and Bland Altman. Diagnostic performance was also compared between each parameter calculating the areas under the operator receiver (ROC). Linear models were used to investigate structure-function association between OCT and SAP.Results. Disagreement between OCTs in both MT and GCIPL values was significant. Spectralis values were thicker than Cirrus. Average difference between OCTs was 21.64 μm (SD 4.5) for MT and 9.8 μm (SD 5.4) for GCIPL (p<0.001). Patients differed significantly from controls in both OCTs, in both measurements. MT and GCIPL were negatively associated with MD (p<0.001).Conclusions. Although OCT values were not interchangeable, both machines differentiated patients from controls with statistical significance. Structure-function analysis results were comparable, when either OCT was compared to SAP.

By the method of indirect immunohistochemistry, distribution of transferrin and of transferrin receptor of the type 1 (TFR1) was studied in the formed rat eye retina at the period of early postnatal ontogenesis (from birth to opening of eyelids). It has been established that the character of distribution of these proteins and intensity of specific staining change dependent on the retina formation stage. Retina of the newborn rat is characterized by diffuse transferrin distribution in nuclear retina layer (in the neuroblast layer-NBL) and in the ganglionic cell layer (GCL) as well as in the eye pigment epithelium (PE); relative immunoreactivity to transferrin is not high. At the 5th postnatal day, immunoreactivity to transferrin is maximal and is revealed both in nuclear and in plexiform layers of retina and in the eye PE, the greatest signal being characteristic of NBL. At the 10th postnatal day the transferrin signal intensity in retina decreases, specific staining is revealed in GCL, PE, and in the area of formed outer segments of photoreceptors. At the 15th postnatal day, transferrin is revealed in GCL, in outer and inner photoreceptor segments and in the eye PE. TFR1 is present in all retina layers at all stages of the retina formation; the relative immunoreactivity to TFR1 sharply rises beginning from the 10th postnatal day; correlation between distribution of transferrin and TFR1 is detected in the entire retina of newborn rats as well as in the external retina area at subsequent stages of its development. A possible role of transferrin at various stages of formation of retina is discussed.

The aim of the study was to investigate the thickness and volume profiles of each retinal layer in postoperative patients with epiretinal membranes. Twenty-four patients who underwent pars plana vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane were included. The best corrected visual acuity, thickness, and volume were recorded from the medical records through a retrospective review. Spectral domain optical coherence tomography was used to measure the average thickness and volume of each retinal layer before surgery and 6 months postoperatively. All 24 patients were monitored for 60 months after surgery. In all Early Treatment Diabetic Retinopathy Study (ETDRS) subfields, the thickness and volume of the retinal nerve fiber layer and the inner retinal layer decreased significantly. In contrast, the thickness and volume of the ganglion cell layer, inner nuclear layer, inner plexiform layer, and outer plexiform layer only decreased in some ETDRS subfields. Finally, there was no significant change in the thickness or volume of the outer nuclear layer (ONL), retinal pigment epithelium (RPE), and photoreceptor layers in all ETDRS subfields. The thickness and volume of the inner retina layer decreased significantly after pars plana vitrectomy using ILM peeling. However, there was no significant change in the thickness and volume of the outer retinal layers (ONL, RPE, and photoreceptor) after surgery.

The distribution of hyaluronan (HA) in the posterior eye wall from the vitreous through the sclera, with special consideration to localization in the retina and interphotoreceptor matrix (IPM), was evaluated in mouse tissues using an HA specific probe (bHABC, biotinylated hyaluronan binding complex). The vitreous body was positive for HA, as was Bruch's membrane, expansive areas within the choroid, sclera and perimysial connective tissue of extraocular muscle. No HA-staining was detected in the IPM or in any other retina layer except for the basal lamina (inner limiting membrane of the retina) which abuts the vitreous. Predigestion of sections with trypsin or chondroitinase ABC before bHABC application did not produce additional HA-staining in the retina or IPM.

Modeling of the retina in accordance with its physiological structure plays a key role in development of the high-performance image processing methods for sight restoration studies. In the literature, some Gaussian filter based artificial retinal processing models have been presented. In this study, as an alternative method to models which does not consider the characteristics of image content, adaptive DoG filter based artificial retina model that adaptively changes the bandwidths of the DoG filters according to local image data is developed. This model has two layers: the first layer models the interactions between receptors, horizontal and bipolar cells, the second layer models the interactions between bipolar, amacrine and ganglion cells of the retina layer. To evaluate the contribution of the model for image quality, some tests are performed by using video inputs. For this purpose, in these tests, spike counts based reconstructed images obtained by using this model, are analyzed. The retina model developed in this study which includes a 3-Dimensional Two-Stage Adaptive DOG (3D-ADOG) filter and the standard DOG filter based retina model are analyzed by using the statistical parameters of Mean Gray Level, Universal Quality Index and Histogram Similarity Ratio. In addition, the Histogram Similarity Ratio versus time is obtained and shown graphically for each model. From these performance analyses; it is concluded that 3D-ADOG filter-based retina model is closer to the original image in comparison with well-known classical DoG filter-based retina model and retinal implant systems based on this model will provide a better visual perception.

A mathematical framework for estimation of the conductivity map of the retina is presented. The problem is formulated and solved in two-dimensional space considering hypothetical inhomogeneity in the conductivity profile at each layer of the retina in x and y directions. Finite element analysis is used to solve the equation of continuity in steady state to simulate voltage measurements as well as estimate the conductivity map. The results of simulated noisy data for an inhomogeneous retina layer and the fovea, which has a more complicated geometry, are presented. The error study of the estimated conductivity map shows that the error for an inhomogeneous conductivity profile is approximately 2% and the error for calculating the fovea conductivity map is just above 8%. This method can be extended to three-dimensions and can also be used to measure the impedance of different layers of the retina for alternating currents.

We have used Monte Carlo simulation of autofluorescence in the retina to determine that noninvasive detection of nutritional iron deficiency is possible. Nutritional iron deficiency (which leads to iron deficiency anemia) affects more than 2 billion people worldwide, and there is an urgent need for a simple, noninvasive diagnostic test. Zinc protoporphyrin (ZPP) is a fluorescent compound that accumulates in red blood cells and is used as a biomarker for nutritional iron deficiency. We developed a computational model of the eye, using parameters that were identified either by literature search, or by direct experimental measurement to test the possibility of detecting ZPP non-invasively in retina. By incorporating fluorescence into Steven Jacques' original code for multi-layered tissue, we performed Monte Carlo simulation of fluorescence in the retina and determined that if the beam is not focused on a blood vessel in a neural retina layer or if part of light is hitting the vessel, ZPP fluorescence will be 10-200 times higher than background lipofuscin fluorescence coming from the retinal pigment epithelium (RPE) layer directly below. In addition we found that if the light can be focused entirely onto a blood vessel in the neural retina layer, the fluorescence signal comes only from ZPP. The fluorescence from layers below in this second situation does not contribute to the signal. Therefore, the possibility that a device could potentially be built and detect ZPP fluorescence in retina looks very promising.

In the paper we present an algorithm for the identification of retina layers using the Canny edge detection for images obtained with OCT (Optical Coherence Tomography) Copernicus. The developed algorithm is an extension of the approaches covered in [4] and allows the identification and detection of hyaline-retinal border layers, the retina and other. The algorithm was implemented in the Matlab environment and the C language.

Reflection of laser radiation from the upper and lower bound of the quasi-crystal layers by retina (a layer of nervous fibers and photoreceptor disks) in the framework of holographic model of physiological optics was considered. Cases of dark-adapted and completely decolorized photoreceptor disks were considered. Two problems were considered for reflection from the lower bounds: (1) ordinary wave reflection from crystal-isotropic media interface; (2) extraordinary wave reflection from crystal-isotropic media interface. Graphs for two components of back-scattered field, depending upon the laser incidence angle at retina and the angle between incidence plane and optical axis of retina layer nerve fibers were obtained. Cases of dark-adapted and completely decolorized photoreceptor disks were considered. The results obtained may be used in laser methods for diagnostics and treatment of ophthalmologic diseases.

MRI has recently been used for noninvasive examination of retinal structure and function in rats and cats. However, the advantages of quantitative high-resolution MRI of retina from mice have not yet been explored. In the present study, T(1) and T(2) relaxation time constants and the directional apparent diffusion coefficient (ADC) in the retina of C57/BL6 mice were measured. Three MR-detected retina layers and a MR-detected choroid layer were observed on both T(1)- and T(2)-weighted images at an image resolution of 47 x 47 x 400 microm(3). The significantly higher ADC parallel to than that perpendicular to the optic nerve in the MR-detected outer retina layer at the central retina reflects the known cellular organization of the photoreceptor cells. This study establishes, for the first time, normative metrics of T(1), T(2), and ADC of the mouse retina. These MR parameters are expected to be useful in future evaluation of developmental and pathological alterations of retinal cell layers in mice.

The expression levels of rod opsin and glial fibrillary acidic protein (GFAP) capture important structural changes in the retina during injury and recovery. Quantitatively measuring these expression levels in confocal micrographs requires identifying the retinal layer boundaries and spatially corresponding the layers across different images. In this paper, a method to segment the retinal layers using a parametric active contour model is presented. Then spatially aligned expression levels across different images are determined by thresholding the solution to a Dirichlet boundary value problem. Our analysis provides quantitative metrics of retinal restructuring that are needed for improving retinal therapies after injury.

A holographic model of physiological optics, declaring Fourier hologram of light intensity formation and registering in eyes of higher animal was developed. Computer simulation of light propagation in quasi crystal retina layers and graphs for intensity distribution of ordinary and extraordinary rays in retina, depending upon the light angle at retina, the angle between incidence plane and optical axis of retina layer nerve fibers, and the plane of light polarization was conducted. Computer simulation of Haidenger effect was carried out. A very good correspondence between theoretical calculation and Haidinger brushes, observed in experiment. Was obtained. This confirms the validity of holographic model of physiological optics.

With the help of adaptive optics (AO) technology, cellular level imaging of living human retina can be achieved. Aiming to reduce distressing feelings and to avoid potential drug induced diseases, we attempted to image retina with dilated pupil and froze accommodation without drugs. An optimized liquid crystal adaptive optics camera was adopted for retinal imaging. A novel eye stared system was used for stimulating accommodation and fixating imaging area. Illumination sources and imaging camera kept linkage for focusing and imaging different layers. Four subjects with diverse degree of myopia were imaged. Based on the optical properties of the human eye, the eye stared system reduced the defocus to less than the typical ocular depth of focus. In this way, the illumination light can be projected on certain retina layer precisely. Since that the defocus had been compensated by the eye stared system, the adopted 512 × 512 liquid crystal spatial light modulator (LC-SLM) corrector provided the crucial spatial fidelity to fully compensate high-order aberrations. The Strehl ratio of a subject with −8 diopter myopia was improved to 0.78, which was nearly close to diffraction-limited imaging. By finely adjusting the axial displacement of illumination sources and imaging camera, cone photoreceptors, blood vessels and nerve fiber layer were clearly imaged successfully.

PURPOSE To investigate the tomographic characteristics of the outer retina and choroid and their relationship with visual acuity in X-linked juvenile retinoschisis (XLRS) patients using spectral-domain optical coherence tomography (SD-OCT). METHODS In this retrospective, observational, case-control study, we analyzed 20 eyes of 10 patients with XLRS using SD-OCT. The clinical and tomographic features of the outer retina, including the external limiting membrane (ELM), inner segment/outer segment (IS/OS) junction, cone cell outer segment tips (COST) line, photoreceptor outer segment (PROS) length, and choroid, were evaluated. As controls, 40 age-, sex-, and refraction-matched healthy eyes (1:2 matched) were randomly selected and imaged in parallel. RESULTS The most prevalent area of abnormality in the outer retina layer of our patients was the outer plexiform layer (OPL; 60% of all affected eyes) and COST line (75% of all affected eyes). On average, the subfoveal choroid and PROS lengths were 35 μm thicker and 19 μm thinner, respectively, in XLRS patients (P = 0.084 and P < 0.001, respectively). A dominant IS/OS junction, COST line defects, and PROS length were related to patient best-corrected visual acuity (BCVA; P = 0.029, P = 0.001, and P < 0.001, respectively) by univariate analysis. Cone cell outer segment tips line defect and PROS length were the only factors related to BCVA in multivariate analysis (P = 0.028 and 0.003, respectively). CONCLUSIONS Outer plexiform layer and photoreceptor microstructure defects are frequent in XLRS patients. Cone cell outer segment tips line defects and shortened PROS lengths as well as other photoreceptor microstructure defects may be closely related to poor vision in XLRS.

The retinal thickness analyzer (RTA) is an ophthalmic imaging instrument for the measurement and mapping of the thickness of the retina. The RTA is based on the principle of optical triangulation. A laser beam, which is offset from the optical axis of the eye, is projected onto the retina so that it hits the retina at an angle relative to the optical axis. The light reflected back from this beam at the retina is imaged onto a CCD camera through an off-axis aperture opposite the offset of the incident beam. This cause the light reflected from different layers of the retina to be offset in the image. The size of the offset of light from a retina layer is a measure of the depth of the layer in the retina. Image processing algorithms, which is used to analyze the image for determination of the retinal thickness and structure. A curve fitting procedure based on a physical model of retinal light scattering is used. Thickness determination repeatability is 13 microns (1 sigma). For the registration of thickness measurements, conventional images of the retina are acquired in coincidence with the thickness measurements. Feature extraction algorithms are used to register these images relative to each other and to locate the thickness data on the retina.

During eye development, optic vesicles evaginate laterally from the neural tube and develop into two bilayered eye cups that are composed of an outer pigment epithelium layer and an inner neural retina layer. Despite their similar embryonic origin, the pigment epithelium and neural retina differentiate into two very distinct tissues. Previous studies have demonstrated that the developmental potential of the pigmented epithelial cells is not completely restricted; until embryonic day 4.5 in chick embryos, the cells are able to switch their phenotype and differentiate into neural retina when treated with fibroblast growth factors (FGF) (Park, C. M., and Hollenberg, M. J. (1989). Dev. Biol. 134, 201-205; Pittack, C., Jones, M., and Reh, T. A. (1991). Development 113, 577-588; Guillemot, F. and Cepko, C. L. (1992). Development 114, 743-754). These studies motivated us to test whether FGF is necessary for neural retina differentiation during the initial stages of eye cup development. Optic vesicles from embryonic day 1.5 chick were cultured for 24 hours as explants in the presence of FGF or neutralizing antibodies to FGF2. The cultured optic vesicles formed eye cups that contained a lens vesicle, neural retina and pigmented epithelium, based on morphology and expression of neural and pigmented epithelium-specific antigens. Addition of FGF to the optic vesicles caused the presumptive pigmented epithelium to undergo neuronal differentiation and, as a consequence, a double retina was formed. By contrast, neutralizing antibodies to FGF2 blocked neural differentiation in the presumptive neural retina, without affecting pigmented epithelial cell differentiation. These data, along with evidence for expression of several FGF family members and their receptors in the developing eye, indicate that members of the FGF family may be required for establishing the distinction between the neural retina and pigmented epithelium in the optic vesicle.