In this paper, we propose a novel classification model for automatically identifying individuals with age-related macular degeneration (AMD) or Diabetic Macular Edema (DME) using retinal features ...from Spectral Domain Optical Coherence Tomography (SD-OCT) images. Our classification method uses retinal features such as the thickness of the retina and the thickness of the individual retinal layers, and the volume of the pathologies such as drusen and hyper-reflective intra-retinal spots. We extract automatically, ten clinically important retinal features by segmenting individual SD-OCT images for classification purposes. The effectiveness of the extracted features is evaluated using several classification methods such as Random Forrest on 251 (59 normal, 177 AMD and 15 DME) subjects. We have performed 15-fold cross-validation tests for three phenotypes; DME, AMD and normal cases using these data sets and achieved accuracy of more than 95% on each data set with the classification method using Random Forrest. When we trained the system as a two-class problem of normal and eye with pathology, using the Random Forrest classifier, we obtained an accuracy of more than 96%. The area under the receiver operating characteristic curve (AUC) finds a value of 0.99 for each dataset. We have also shown the performance of four state-of-the-methods for classification the eye participants and found that our proposed method showed the best accuracy.
Retinal visual prostheses ("bionic eyes") have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant ...such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration.
Clinicaltrials.gov NCT01603576.
Emergence of the high‐resolution optical coherence tomography has allowed better delineation of retinal layers, and many of the anatomical correlations of these layers have now been agreed upon. ...However, some anatomical correlates still remain contentious, such as the second hyper‐reflective band, which is now termed ellipsoid zone. Despite the lack of consensus of the actual origin of the ellipsoid zone, there has been much interest in evaluating its integrity and intensity in different disease processes. This review paper aims to provide an overview of the ellipsoid zone and its clinical and research applications.
To compare the effectiveness of low-luminance visual acuity (LLVA) and microperimetry as functional measures in early stages of age-related macular degeneration (AMD).
Prospective cross-sectional ...study.
One hundred seventy-nine participants with a clinical spectrum of non-neovascular AMD and 26 control participants.
Best-corrected visual acuity (BVCA), LLVA, and microperimetric retinal sensitivity were measured on 1 eye of all participants. Low-luminance deficit (LLD) was calculated as the difference between LLVA and BCVA. The functional parameters were compared between 6 clinical severity groups (from controls to non-foveal geographic atrophy GA), and the relationships and magnitude of these parameters were determined and compared.
Visual acuity parameters (BCVA, LLVA, and LLD) and central retinal sensitivity.
Best-corrected visual acuity, LLVA, and central retinal sensitivity were reduced significantly for all AMD clinical severity groups when compared with control participants (P ≤ 0.002), except for those with drusen between 63 and 125 μm (P ≥ 0.107). However, LLD was not significantly different from control participants in all groups (P ≥ 0.073), except in the non-foveal GA group (P = 0.008). A significant positive relationship between central retinal sensitivity and LLD (R = 0.613; P < 0.001), but not BCVA, suggests that there is a trend for LLVA to detect a greater extent of functional deficit than BCVA in eyes with increasingly poorer retinal sensitivity. However, the results of the linear regression models estimated central retinal sensitivity to be 6.1, 3.7, and 5.1 standard deviations (SDs) less than normal by the time BCVA, LLVA, and LLD, respectively, were 2 SDs less than normal.
In early stages of AMD, LLVA did not detect a greater extent of functional deficit than BCVA when compared with control participants. Although there was a trend for LLVA to be more effective at detecting foveal deficits than BCVA in eyes with increasingly poorer retinal sensitivity, both visual acuity measures were much less sensitive compared with microperimetry.
To characterize the pathological changes preceding the development of drusen-associated atrophy in eyes with age-related macular degeneration (AMD) using spectral-domain optical coherence tomography ...(SD-OCT).
Longitudinal and cross-sectional retrospective observational study.
A total of 181 participants with intermediate AMD in at least 1 eye (141 unilateral, 40 bilateral) were assessed longitudinally. A total of 230 participants with bilateral intermediate AMD (40 longitudinal participants with an additional 190 participants) were analyzed cross-sectionally.
Spectral-domain OCT, color fundus photography (CFP), near-infrared reflectance, and fundus autofluorescence imaging were performed in all participants at cross-section and every 3 months for up to 30 months in the longitudinal study. Spectral-domain OCT volume scans were examined for features that portend the development of drusen-associated atrophy, and the topography, prevalence, and risk factors of these features were determined through cross-sectional analysis.
The pathological features on SD-OCT preceding the development of drusen-associated atrophy and the characteristics of these features.
Twenty areas from 16 eyes of 16 participants developed drusen-associated atrophy after an average of 20 months (range, 8-30 months). Spectral-domain OCT features unique in these areas included: subsidence of the outer plexiform layer (OPL) and inner nuclear layer (INL), and development of a hyporeflective wedge-shaped band within the limits of the OPL. These characteristics were termed "nascent geographic atrophy" (nGA), describing features that portend the development of drusen-associated atrophy. Cross-sectional examination of participants with bilateral intermediate AMD revealed that independent risk factors for the presence of nGA included the presence of pigmentary changes (odds ratio OR, 16.84; 95% confidence interval CI, 2.42-117.24) and nGA in the fellow eye (OR, 4.15; 95% CI, 1.12-15.34); nGA was present in 21.9% of participants with drusen >125 μm and pigmentary changes in both eyes.
This study identified pathological changes occurring before the development of drusen-associated atrophy using SD-OCT, which we defined as nGA. Although nGA is undetectable on CFP, it is important for determining the risk of future vision loss in AMD and could be used as an earlier surrogate end point in interventional trials targeting the early stages of AMD.
To compare static rod function obtained with and without photobleach in control and intermediate age-related macular degeneration (iAMD) participants with and without subretinal drusenoid deposits ...(SDD).
In this cross-sectional study, retinal sensitivities within the central 24° retina were obtained twice using a dark-adapted chromatic perimeter, both with 505- and 625-nm stimuli. Tests were performed after 30 minutes of dark-adaptation either with or without a preceding photobleach. Multimodal imaging was performed to grade AMD and SDD status, and other retinal changes considered being risk factors for progression to late AMD. The sensitivity difference between both stimuli was used to assess rod function. The average point wise sensitivity difference (PWSD) was compared among the study groups.
Twenty-nine control subjects and 20 iAMD without SDD and 17 iAMD with SDD cases were recruited. The average PWSD of the SDD group was significantly reduced (more with photobleach) compared with that of the control (P < 0.001) and no-SDD groups (P < 0.001), but only within the central 8°. The average PWSD of the non-SDD group was also reduced compared with the control group but only for measurements with photobleach (P = 0.020). There was no difference in average PWSD between the presence and absence of hyperreflective foci and/or nascent geographic atrophy in iAMD eyes without SDD (P = 0.60) or with SDD (P = 0.12).
iAMD eyes with SDD are associated with worse static rod function compared with eyes without SDD. The greatest abnormality in rods is observed within the central 8° and when tested with a preceding photobleach.
To determine the relationship between structural parameters of the outer retina on spectral-domain optical coherence tomography (SD-OCT) and microperimetric retinal sensitivity in early stages of ...age-related macular degeneration (AMD).
Prospective, observational study.
Seventy-five eyes of 75 participants with early stages of AMD (drusen ≥ 125 μm, with/without pigmentary abnormalities) and 25 control participants of a similar age.
Participants underwent microperimetry testing and high-resolution SD-OCT scans. Structural parameters at 5 central points (0°, 1°, and 2.33° nasal and temporal to the fovea along the horizontal axis) corresponding to areas tested by microperimetry were compared. Structural parameters included outer segment (OS) length, thickness and elevation of the retinal pigment epithelium (RPE) band, grading of the inner-segment ellipsoid (ISe) band integrity, and presence of hyperreflective foci (HF).
Relationship between structural parameters and retinal sensitivity.
Retinal sensitivity was significantly correlated with RPE elevation (P<0.001), ISe grading (P<0.001), and presence of HF (P ≤ 0.018) at all test points, but not with OS length (P ≥ 0.093) or RPE thickness (P ≥ 0.125). However, multiple linear regression analyses revealed that only ISe grading (P ≤ 0.011) and RPE elevation (P ≤ 0.030) remained significantly associated with retinal sensitivity at all points. By using a simple linear model incorporating ISe grading and RPE elevation to predict values of retinal sensitivity, the 95% limits of agreement between the predicted and the actual value was ± 3.83 dB.
The integrity of the ISe band and drusen-associated RPE elevation are significant independent predictors of microperimetric retinal sensitivity. Our findings imply that these 2 structural parameters may be surrogate markers of retinal function in the early stages of AMD.
Diabetic retinopathy (DR) is a retinal microvascular disease characterized by inflammatory and angiogenic pathways. In this study, we evaluated NLRP3 inflammasome in a double transgenic mouse model, ...Akimba (Ins2
xVEGF
), which demonstrates hyperglycemia, vascular hyperpermeability and neovascularization seen in the proliferative DR. Retinal structural integrity, vascular leakage and function were examined by fundus photography, fluorescein angiography, optical coherence tomography, retinal flat mounts, laser speckle flowgraphy (LSFG), and electroretinography in Akimba and its parental strains, Akita (Ins2
) and Kimba (trVEGF029) mice. Inflammatory mechanisms involving NLRP3 inflammasome were investigated using real time-PCR, immunohistochemistry, ELISA and western blots. We observed an increased vascular leakage, reduced retinal thickness, and function in Akimba retina. Also, Akimba retina depicts decreased relative flow volume measured by LSFG. Most importantly, high levels of IL-1β along with increased NLRP3, ASC, and Caspase-1 at mRNA and protein levels were observed in Akimba retina. However, the in vivo functional role remains undefined. In conclusion, increased activation of macroglia (GFAP), microglia (Iba-1 and OX-42) and perivascular macrophages (F4/80 and CD14) together with pro-inflammatory (IL-1β and IL-6) and pro-angiogenic markers (PECAM-1, ICAM-1, VEGF, Flt-1, and Flk-1), suggested a critical role for NLRP3 inflammasome in the Akimba mouse model depicting advanced stages of DR pathogenesis.
To investigate the safety and efficacy of subretinal injection of human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) ...rats.
RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies.
No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells.
Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies.
•Human visual processing has biased sensitivities to gratings in various orientations.•Adults are usually least sensitive to oblique gratings (Oblique Effect).•Children are usually least sensitive to ...horizontal gratings (Horizontal Effect).•The horizontal effect is still present after four months with normal maturation.•Poor visual development may produce alternative patterns of meridional anisotropies.
It is important to understand the development of meridional anisotropies in neurotypical children since those with poor visual development, such as amblyopia, can have different patterns of meridional anisotropies. While the oblique effect is usually observed in adults, neurotypical children who have normal 20/20 visual acuity tend to demonstrate a horizontal effect electrophysiologically. In this longitudinal study, orientation-specific visual evoked potentials (osVEPs) and psychophysical grating acuity were used to investigate the changes in the meridional anisotropies in children aged 3.8 to 9.2 years over two visits averaging four months apart. While it was hypothesized that the electrophysiological horizontal effect may shift towards an oblique effect, it was found that the electrophysiological horizontal effect persisted to be present in response to the suprathreshold moderate contrast 4 cycles-per-degree grating stimuli. Psychophysical grating acuity, however, demonstrated an oblique effect when assessed binocularly. In addition, a significant effect of visit, representing an increase in the average age over this period, was observed in the average osVEP C3 amplitudes (4.5 μV) and psychophysical grating acuity (0.28 octaves or approximately 1-line on the logMAR chart). These findings are relevant when evaluating amblyopia treatments and interventions, as it confirms the necessity to take into account of the effect of normal maturation and learning effects when evaluating young children. Special attention should also be given to children with early-onset myopia and high astigmatism even when their visual acuity is 20/20 as the electrophysiological findings are suggestive of poor visual development, which warrants further investigation.
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