Retinal Area Research Articles

Retinal and Choroidal Alterations in Diabetic Retinopathy Treatment using Subthreshold Panretinal Photocoagulation with Endpoint Management Algorithm: A Secondary Analysis of a Randomized Clinical Trial.

The aim of this study was to compare retinal and choroidal alterations in eyes with severe nonproliferative diabetic retinopathy (NPDR) after panretinal photocoagulation (PRP), using conventional pattern scan laser (PASCAL) and PASCAL with endpoint management (EPM). This was a post hoc analysis of a paired randomized clinical trial. Bilateral treatment-naïve eyes of an individual with symmetric severe NPDR were randomly allocated into the threshold PRP group and subthreshold EPM PRP group. Patients had follow-up visits at 1, 3, 6, 9, and 12months post-treatment. The retinal thickness (RT), choroidal thickness (CT), choroidal area, and choroidal vascularity index (CVI) were compared between the two groups and among different time points within the same group. Seventy eyes of 35 patients with diabetes mellitus (DM) were finally included for analysis at the 6- and 12-month visits, respectively. At 3 and 6months post-treatment, the RT in the subthreshold EPM PRP group was significantly thinner than that in the threshold PRP group. CT, stromal area, and luminal area were reduced earlier in the threshold PRP group than in the subthreshold EPM PRP group. CVI was not significantly different within the same group or between groups at most time points. At 12months post-treatment, retinal thickening and choroidal disturbance may be slightly less severe and more delayed in eyes receiving PRP using PASCAL with EPM than in those receiving PRP using conventional PASCAL. The EPM algorithm may be a good alternative in PRP when treating severe NPDR. ClinicalTrials.gov identifier, NCT01759121.

Comparison of quantitative assessment and efficiency of diabetic retinopathy diagnosis using ETDRS seven-field imaging and two ultra-widefield imaging.

This study compared the efficiency of diabetic retinopathy (DR) diagnosis and differences in the relative visible retinal area among the Early Treatment Diabetic Retinopathy Study (ETDRS) seven-field, ultra-widefield (UWF)-Optos, and UWF-Clarus fundus imaging methods. This was a prospective and clinic-based comparative study. All patients underwent three fundus examinations, and all images were graded using the ETDRS severity scale. We compared and analysed the agreement of DR severity and the relative visible retinal area among the three fundus examination methods, and the number and type of lesions outside the ETDRS seven-field (peripheral lesions) between the two UWF imaging methods. A total of 202 patients (386 eyes) were included. Weighted kappa for the agreement between ETDRS seven-field and blinded Optos images was 0.485; between ETDRS seven-field and blinded Clarus images, 0.924; and between blinded Optos and Clarus images, 0.461. Blinded Clarus showed excellent performance when a ETDRS scale was used for grading the images. The relative visible retinal area for ETDRS seven-field images was 195 ± 28 disc area (DA); single Optos images, 371 ± 69 DA; single Clarus images, 261 ± 65 DA; two-montage Clarus images, 462 ± 112 DA; and four-montage Clarus images, 598 ± 139 DA. The relative visible retinal area was statistically significant between any two of the imaging systems used. In total, 2015 and 4200 peripheral lesions were detected in single Optos and Clarus images, respectively (P < 0.001). These peripheral lesions on two UWF images suggested a more severe DR level in approximately 10% and 12% of eyes, respectively. UWF-Clarus fundus imaging offers a suitable assessment approach for DR severity; it could improve DR diagnosis and has the potential to replace ETDRS seven-field imaging after additional clinical trials.

ARA-net: an attention-aware retinal atrophy segmentation network coping with fundus images.

Accurately detecting and segmenting areas of retinal atrophy are paramount for early medical intervention in pathological myopia (PM). However, segmenting retinal atrophic areas based on a two-dimensional (2D) fundus image poses several challenges, such as blurred boundaries, irregular shapes, and size variation. To overcome these challenges, we have proposed an attention-aware retinal atrophy segmentation network (ARA-Net) to segment retinal atrophy areas from the 2D fundus image. In particular, the ARA-Net adopts a similar strategy as UNet to perform the area segmentation. Skip self-attention connection (SSA) block, comprising a shortcut and a parallel polarized self-attention (PPSA) block, has been proposed to deal with the challenges of blurred boundaries and irregular shapes of the retinal atrophic region. Further, we have proposed a multi-scale feature flow (MSFF) to challenge the size variation. We have added the flow between the SSA connection blocks, allowing for capturing considerable semantic information to detect retinal atrophy in various area sizes. The proposed method has been validated on the Pathological Myopia (PALM) dataset. Experimental results demonstrate that our method yields a high dice coefficient (DICE) of 84.26%, Jaccard index (JAC) of 72.80%, and F1-score of 84.57%, which outperforms other methods significantly. Our results have demonstrated that ARA-Net is an effective and efficient approach for retinal atrophic area segmentation in PM.

PREDICTION OF DIABETIC RETINOPATHY SEVERITY USING A COMBINATION OF RETINAL NEURODEGENERATION AND CAPILLARY NONPERFUSION ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To generate a prediction model of diabetic retinopathy (DR) severity stages based on retinal neurodegeneration and capillary nonperfusion area (NPA) detected using optical coherence tomography (OCT) and OCT angiography (OCTA). A total of 155 treatment-naïve eyes were retrospectively included. Macular ganglion cell/inner plexiform layer (mGCIPL) thickness in six macular regions was measured. A custom algorithm was used to calculate capillary NPA from 3 × 3 mm 2 and 12 × 12 mm 2 field OCTA images. The region of interest was selected as circular areas of 3 mm and 12 mm diameter and divided into six subsections. Classification and regression tree analysis identified the best predictors to discriminate between the five DR stages. Inferotemporal sector showed the largest mean NPA, and the inferior hemispheric NPA was significantly larger compared with the superior hemisphere. The mean mGCIPL thickness was significantly correlated with NPA of 12 × 12 mm 2 field in participants with early stage DR. Inferior hemispheric NPA of 12 × 12 mm 2 field and mean mGCIPL thickness were the two best variables to discriminate no DR versus mild nonproliferative DR (NPDR) and mild versus moderate NPDR (accuracy: 88.8% and 93.5%). Meanwhile, a combination of NPA of 12 × 12 mm 2 and 3 × 3 mm 2 fields was the best prediction model to discriminate moderate versus severe NPDR and severe NPDR versus PDR (accuracy: 91.8% and 94.1%). A combination model of capillary NPA and mGCIPL thickness may be a novel biomarker for predicting DR severity. Capillary nonperfusion seems to initially occur in the midperipheral retina with macular neurodegeneration and progress posteriorly.

Foveal avascular zone segmentation using deep learning-driven image-level optimization and fundus photographs.

The foveal avascular zone (FAZ) is a retinal area devoid of capillaries and associated with multiple retinal pathologies and visual acuity. Optical Coherence Tomography Angiography (OCT-A) is a very effective means of visualizing retinal vascular and avascular areas, but its use remains limited to research settings due to its complex optics limiting availability. On the other hand, fundus photography is widely available and often adopted in population studies. In this work, we test the feasibility of estimating the FAZ from fundus photos using three different approaches. The first two approaches rely on pixel-level and image-level FAZ information to segment FAZ pixels and regress FAZ area, respectively. The third is a training mask-free pipeline combining saliency maps with an active contours approach to segment FAZ pixels while being trained on image-level measures of the FAZ areas. This enables training FAZ segmentation methods without manual alignment of fundus and OCT-A images, a time-consuming process, which limits the dataset that can be used for training. Segmentation methods trained on pixel-level labels and image-level labels had good agreement with masks from a human grader (respectively DICE of 0.45 and 0.4). Results indicate the feasibility of using fundus images as a proxy to estimate the FAZ when angiography data is not available.

Spherical Aberration and Accommodative Insufficiency: Is There a Link?

Given the relationship between spherical aberrations and accommodation, the study of these aberrations can be helpful to understand accommodative response in subjects with accommodative dysfunctions. The purpose of this study was to evaluate on-axis and off-axis changes of primary and secondary spherical aberrations, Z(4,0) and Z(6,0), with accommodation in subjects with accommodative insufficiency (AI). Ten subjects with AI and eleven without any accommodative dysfunction (control) participated in this study. On-axis defocus Z(2,0), Z(4,0), and Z(6,0) were obtained in both groups with a Hartmann–Shack aberrometer for the unaccommodated state and with 1.00 D, 2.44 D, 3.83 D, and 4.73 D of accommodative stimuli. Z(4,0) and Z(6,0) were also measured on 11.5° and 23° temporal, nasal, superior, and inferior retinal areas for unaccommodated state and for 2.44 D of accommodative stimulus. In the control group, Z(4,0) became more negative with accommodation and Z(6,0) became more positive, as was expected according to previous studies. This tendency was not observed in the group of subjects with AI group for Z(4,0) or for Z(6,0). No differences on off-axis Z(4,0) and Z(6,0) were observed between the groups. The changes of spherical aberrations with accommodation seem different in subjects with AI compared to those without any accommodative dysfunction. Those with AI do not present a decrease in Z(4,0) and an increase in Z(6,0) with accommodation as occurs in eyes without this type of dysfunction. Understanding how the optics of the eye changes with accommodation can be helpful to understand the origin of accommodative dysfunctions.

“White without Pressure” Associated with Other Degenerations: Features of Vitreoretinal Interface on OCT Scans (Clinical Case)

“White without pressure” warrants special attention from ophthalmologists due to the lack of consensus on its etiopathogenesis and associated risk of rhegmatogenous retinal detachment. “White without pressure” appears in various quadrants of the fundus as an area white to gray in color. It is more common in persons with high myopia.The paper presents a clinical case of a 19-year-old male with an association between “white without pressure”, “dark without pressure”, vitreoretinal tuft and symptomatic floaters in the left eye. OCT scanning (SOLIX) was employed to assess the vitreoretinal interface. OCT revealed the intraretinal location of “white without pressure” and “dark without pressure” degenerations without vitreoretinal traction. “White without pressure” degeneration is hyperreflective at the level of the outer retina in the photoreceptor ellipsoid and myoid zones, and “dark without pressure” is hyporeflective at this level. Vitreoretinal tuft is a vitreoretinal degeneration located at the level of the inner limiting membrane. It was detected as a hyperreflective site with vitreoretinal adhesion leading to traction and thickening of the corresponding retinal area. The combination of the three degenerations poses a risk of rhegmatogenous retinal detachment due to the presence of the vitreoretinal tuft.

Retinopathy of prematurity protection conferred by uteroplacental insufficiency through erythropoietin signaling in an experimental Murine Model.

Recent clinical studies suggest that preeclampsia, characterized by uteroplacental insufficiency (UPI) and infant intrauterine growth restriction (IUGR), may be protective against retinopathy of prematurity (ROP) in preterm infants. Experimental models of UPI/IUGR have found an association of erythropoietin (EPO) with less severe oxygen-induced retinopathy (OIR); however, it is unclear if EPO/EPO receptor (EPOR) signaling was involved. We hypothesized that maternal UPI and resultant infant IUGR would protect against features of ROP through EPO/EPOR signaling. We compared transgenic mice with hypoactive EPOR signaling (hWtEPOR) to littermate wild-type mice (mWtEpoR) in a novel combined model of IUGR and ROP. Thromboxane A2 (TXA2) was infused into pregnant C57Bl/6J dams to produce UPI/IUGR; postnatal pups and their foster dams were subjected to a murine OIR model. Following hyperoxia, hematocrits were similar between littermate wild-type (mWtEpoR) TXA2/OIR and vehicle/OIR pups. mWtEpoR TXA2/OIR had increased serum EPO, retinal EPO and VEGF, and decreased avascular retinal area (AVA) compared to vehicle/OIR pups. In comparison to the mWtEpoR TXA2/OIR pups, AVA was not reduced in hWtEPOR TXA2/OIR pups. Our findings provide biologic evidence that UPI/OIR-induced endogenous EPOR signaling confers protection against hyperoxia-induced vascular damage that may be related to pathophysiology in ROP. Maternal preeclampsia and infant growth restriction confer retinovascular protection against high oxygen-induced damage through endogenous erythropoietin signaling.

Myopia in retinopathy of prematurity

Myopic changes in the fundus have been known to have a protective role in vasculopathy. The reduced metabolic demands prevent the progression of vascular disorders in myopic eyes. However, this theory might not be applicable for myopia in retinopathy of prematurity (ROP) babies. An increased retinal surface area in an eye with a longer axial length might aggravate the progression of ROP. We discuss two cases of unilateral progression of ROP in a longer axial length eye.

Analysis of Blood Flow in the Macula and Optic Nerve Head in Healthy Young Volunteers Using Laser Speckle Flowgraphy.

To assess optic nerve head (ONH) and macular blood flow in young healthy volunteers using laser speckle flowgraphy (LSFG). This is a prospective single-center study conducted at the Department of Ophthalmology, University Hospital Zurich from May to November 2021. Young, healthy men aged ≥ 18 years without ocular or systemic diseases were included. A corrected visual acuity (VA) of 0.0 logMAR or better in both eyes and an intraocular pressure (IOP) of 21 mmHg or lower were required for inclusion. Subjects exceeding a spherical equivalent (SE) of ± 6 diopters (dpt) were excluded. Blood flow in the macula and the ONH was recorded using the Nidek LSFG RetFlow device (Nidek Company, Ltd., Hirioshi-cho, Japan). Laser power was set to 0.5 Millivolts (mV). Mean blur rate (MBR) was recorded as a parameter for blood flow. MBR is a calculated parameter that represents relative blood flow velocity correlated with the real anatomical blood flow rate. Colored heat maps of the recorded retinal area were generated automatically by the RetFlow device. Final analyses included 83 eyes of 43 male volunteers. Mean age was 21.9 years (SD ± 1.5, range: 20 to 29). Mean corrected VA was - 0.1 logMAR (SD ± 0.05, range: - 0.2 to 0.0), mean IOP was 15.4 mmHg (SD ± 2.5, range: 8.5 to 18.5), and mean SE was - 0.3 dpt (SD ± 1.2, range: - 5.0 to 1.2). Mean ONH MBR was 37.44 (SD ± 7.9, range: 22.5 to 53.5) and mean macular MBR was 27.8 (SD ± 9.7, range: 6.4 to 57.7). Pearson's Test showed a strong correlation between macular and papillary blood flow (p < 0.05, coefficient: 0.647). This study provides both ONH and macular blood flow data in a healthy young male population, showing a strong correlation between ONH and macular blood flow in the examined eyes. Further investigations are required to assess the validity of MBR as a parameter for the combined evaluation of retinal blood flow at the macula and ONH in healthy volunteers and patients with various diseases.

Is it useful to do OCTA in coronary artery disease patients to improve SYNTAX-based cardiac revascularization decision?

BackgroundTo investigate retinal and optic disk microcirculation using optical coherence tomography angiography (OCTA) in order to predict related outcomes based on the SYNergy between PCI with TAXUS and Cardiac Surgery (SYNTAX) score (SS) system in coronary artery disease patients. Methods104 patients were grouped based on coronary angiography results: 32 chronic coronary syndrome (CCS) patients, 35 acute coronary syndrome (ACS) patients, and 37 healthy controls. The SS system determined atherosclerosis degree and lesion-related mortality risk, followed by scoring as SYNTAX I score (SS-I) and SYNTAX II score (SS-II). Patients were further subdivided into SS-I, SS-II percutaneous coronary intervention (PCI), and SS-II coronary artery by-pass grafting (CABG) groups. Following a thorough ophthalmological examination, an OCTA Angio Retina mode (6 × 6 mm) automatically quantified retinal and optic disk microcirculation. ResultsThe mean ages did not differ significantly among groups (p = 0.940). The outer retinal select area varied significantly among groups, with the highest values found in ACS patients (p = 0.040). Despite non-significant differences between SS-I patients and healthy controls, the former had lower capillary plexus vessel densities in all regions and in foveal vessel density 300 μm around foveal avascular zone (FD-300) (p>0.05). Vessel densities were lowest in SS-II PCI≥28.5 patients, particularly in whole (p = 0.034) and parafoveal (p = 0.009) superficial capillary plexus, and in FD-300 (p = 0.019). Vessel densities were lowest in SS-II CABG (p = 0.020), and perifoveal (p = 0.017) deep capillary plexus, and in FD-300 (p = 0.003). The outer retina flow area increased the most in SS-II CABG≥25.1 patients (p = 0.020). ConclusionsUsing OCTA, a non-invasive imaging technique, to assess retinal and optic disk microcirculation appears to have the potential to yield significant clinical results in the early diagnosis or prognosis of cardiovascular diseases.

APSified OCT-angiography analysis: Macula vessel density in healthy eyes during office hours.

Optical coherence tomography angiography (OCT-A) can visualize retinal capillary microcirculation non-invasively. In order to investigate potential factors influencing OCT-A diagnostics, the aim of the present study was to determine circadian changes in macular vessel density (VD) in healthy adults during office hours, considering axial length (AL) and subfoveal choroidal thickness (CT). In the prospective study 30 eyes of 30 healthy subjects (mean age 28.7 ± 11.8, range 19-60 years) were recruited who underwent repeated measurements of AL, subfoveal CT and three-layer macula VD (superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP)) on a single day at three predetermined timepoints (9 AM, 3 PM, and 9 PM). For better intra- and interindividual scan comparability, the new Anatomic Positioning System function (APS, part of Glaucoma Module Premium Edition [GMPE], Heidelberg Engineering, Germany) allowing analysis of identical retinal areas, was used for quantitative OCT-A analysis. Overall mean macula VD was unchanged during office hours in SVP, ICP and DCP, respectively (p>0.05). In addition, AL and CT showed no statistically significant changes over time (p>0.05). Rather, a large interindividual variance of VD with different peak time was observed. Contrary to the overall data, sectorial VD changed in dependency of office hours in all layers with an increase of VD in SVP between 9 AM and 9 PM (p = 0.003), in ICP between 3 PM and 9 PM (p = 0.000), in DCP between 9 AM and 9 PM (p = 0.048), and 3 PM and 9 PM (p = 0.000), respectively. Overall mean macula VD, subfoveal CT and AL tended not to show statistically significant changes over time in this cohort, whereas a regional analysis of VD did. Therefore, a circadian influence on capillary microcirculation should be kept in mind. Moreover, the results highlight the importance of a more detailed analysis of VD in different sectors and different vascular layers. In addition, the pattern of diurnal variation could vary inter-individually, thus a patient-specific fluctuation pattern would need to be considered when evaluating these parameters in clinical practice.

Loss of Müller cell glutamine synthetase immunoreactivity is associated with neuronal changes in late-stage retinal degeneration.

A hallmark of photoreceptor degenerations is progressive, aberrant remodeling of the surviving retinal neurons and glia following photoreceptor loss. The exact relationship between neurons and glia remodeling in this late stage of retinal degeneration, however, is unclear. This study assessed this by examining Müller cell dysfunction via glutamine synthetase immunoreactivity and its spatial association with retinal neuron subpopulations through various cell markers. Aged Rd1 mice retinae (P150 - P536, n = minimum 5 per age) and control heterozygous rd1 mice retinae (P536, n = 5) were isolated, fixed and cryosectioned. Fluorescent immunolabeling of glutamine synthetase was performed and retinal areas quantified as having low glutamine synthetase immunoreactivity if proportion of labeled pixels in an area was less than two standard deviations of the mean of the total retina. Other Müller cell markers such as Sox9 and Glial fibrillary acidic protein along with neuronal cell markers Calbindin, Calretinin, recoverin, Protein kinase C-α, Glutamic acid decarboxylase 67, and Islet-1 were then quantified within areas of low and normal synthetase immunoreactivity. Glutamine synthetase immunoreactivity was lost as a function of age in the rd1 mouse retina (P150 - P536). Immunoreactivity of other Müller cell markers, however, were unaffected suggesting Müller cells were still present in these low glutamine synthetase immunoreactive regions. Glutamine synthetase immunoreactivity loss affected specific neuronal populations: Type 2, Type 8 cone, and rod bipolar cells, as well as AII amacrine cells based on reduced recoverin, protein kinase Ca and parvalbumin immunoreactivity, respectively. The number of cell nuclei within regions of low glutamine synthetase immunoreactivity was also reduced suggesting possible neuronal loss rather than reduced cell marker immunoreactivity. These findings further support a strong interplay between glia-neuronal alterations in late-stage degeneration and highlight a need for future studies and consideration in intervention development.

Advances in targeted retinal photocoagulation in the treatment of diabetic retinopathy.

Targeted retinal photocoagulation (TRP) is an emerging laser technology for retinal targeted therapy. TRP can specifically act on unperfused retinal capillaries and retinal intermediate ischemic areas, reduce damage to tissue perfusion areas and panretinal photocoagulation (PRP) complications or adverse events. In this regard, this review discusses the treatment options, efficacy, and latest progress of TRP for diabetic retinopathy (DR) based on randomized controlled trial (RCT), meta-analysis, case review, and other existing studies. In-depth research was conducted on articles about the proposal and development of TRP, its simple application in DR, and combined therapy. In order to review the new progress, application methods, effects, and prospects of TRP in the treatment of DR, the articles related to TRP in the databases of PubMed and Web Of Science since this century were comprehensively analyzed. TRP is effective in treating DR and may become a substitute for PRP in the future. In addition, the treatment regimen of TRP combined with intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs can also be used as a new therapeutic approach to expand the treatment regimen for the treatment of DR, and this combination therapy also has effects on other retinal vascular diseases. With the advancement of technology, TRP has been continuously applied in clinical practice, and its potential benefits have opened up broad prospects for the treatment of DR. The combination therapy of TRP and anti-VEGF is expected to become a new option for patients with DR an retinal diseases.

Optical coherence tomography angiography evaluation of retinal and optic disc microvascular morphological characteristics in retinal vein occlusion.

To evaluate microvascular morphological characteristics of the retina and optic disc (OD) in retinal vein occlusion (RVO) patients using optical coherence tomography angiography (OCTA), compare the results to age- and gender-matched healthy subjects, and determine correlations between OCTA parameters and best-corrected visual acuity (BCVA) and age. In this retrospective study, right eyes of 53 RVO patients and 51 healthy subjects were compared regarding BCVA, as well as superficial and deep capillary plexus (SCP and DCP) vessel densities (VDs), foveal avascular zone (FAZ) parameters, outer retinal and choriocapillaris flow areas, OD whole and peripapillary VDs, and retinal nerve fiber layer thickness (RNFLT). Retinal vein occlusion patients were further divided into subgroups based on therapy and risk factors, and OCTA parameters were compared. Retinal vein occlusion rate or OCTA parameters did not differ significantly by gender (p>0.05). Retinal vein occlusion patients had significantly decreased BCVA, whole, parafoveal and perifoveal SCP and DCP VDs, as well as VDs 300µm area around FAZ (FD-300) than healthy subjects (p<0.001). Their choriocapillaris flow area, RNFLT, whole and peripapillary VDs were also affected. However, FAZ area did not differ significantly between groups. Superior RNFLT (p=0.016) and whole peripapillary VD (p<0.001) differed significantly between laser photocoagulation-treated and non-treated patients. The remaining OCTA parameters revealed no significant differences CONCLUSIONS: The RVO and its therapeutic alternatives may affect both OD and retinal VDs. Given its numerous benefits, it seems that OCTA will be used more frequently in clinics for RVO diagnosis, monitoring, and therapeutic response evaluation.

Structure–function assessment in glaucoma based on perimetric sensitivity and en face optical coherence tomography images of retinal nerve fiber bundles

Many studies have assessed structure–function relations in glaucoma, but most without topographical comparison across the central 30°. We present a method for assessing structure–function relations with en face images of retinal nerve fiber layer (RNFL) bundles allowing topographical comparison across much of this retinal area. Forty-four patients with glaucoma (median age 61 years) were recruited and tested with Optical Coherence Tomography (OCT) and perimetry. Six rectangular volume scans were gathered, and then montaged to provide en face views of the RNFL bundles. We calculated the proportion of locations showing a perimetric defect that also showed an en face RNFL defect; and the proportion of locations falling on an RNFL defect that also showed a perimetric defect. A perimetric defect for a location was defined as a total deviation (TD) value equal to or deeper than -4 dB. We found that the median (IQR) number of locations with abnormal RNFL bundle reflectance that also had abnormal TD was 78% (60%) and for locations with abnormal TD that also had abnormal RNFL bundle reflectance was 75% (44%). We demonstrated a potential approach for structure–function assessment in glaucoma by presenting a topographic reflectance map, confirming results of previous studies and including larger retinal regions.

TRPV4 channels promote vascular permeability in retinal vascular disease

This study aimed to determine the role of transient receptor potential vanilloid 4 (TRPV4), a calcium (Ca2+)-permeable cation channel, in the pathophysiology of retinal vascular disease. The retinal vein occlusion (RVO) murine model was created by irradiating retinal veins using lasers. TRPV4 expression and localization were evaluated in RVO mice retinas. In addition, we examined the effects of TRPV4 antagonists (RQ-00317310, HC-067047, GSK2193874, and GSK2798745) on retinal edema, blood flow, and ischemic areas in RVO mice. Furthermore, changes in the retinal expression of tumor necrosis factor (TNF)-α and aquaporin4 (AQP4) by RQ-00317310 were analyzed using Western blot. We also assessed the barrier integrity of epithelial cell monolayers using trans-endothelial electrical resistance (TEER) in Human Retinal Microvascular Endothelial Cells (HRMECs). The expression of TRPV4 was significantly increased and co-localized with glutamine synthetase (GS), a Müller glial marker, in the ganglion cell layer (GCL) of the RVO mice. Moreover, RQ-00317310 administration ameliorated the development of retinal edema and ischemia in RVO mice. In addition, the up regulation of TNF-α and down-regulation of AQP4 were lessened by the treatment with RQ-00317310. Treatment with GSK1016790A, a TRPV4 agonist, increased vascular permeability, while RQ-00317310 treatment decreased vascular endothelial growth factor (VEGF)- or TRPV4-induced retinal vascular hyperpermeability in HRMECs. These findings suggest that TRPV4 plays a role in the development of retinal edema and ischemia. Thus, TRPV4 could be a new therapeutic target against the pathological symptoms of retinal vascular diseases.

Spatial distribution of metabolites in the retina and its relevance to studies of metabolic retinal disorders

IntroductionThe primate retina has evolved regional specialisations for specific visual functions. The macula is specialised towards high acuity vision and is an area that contains an increased density of cone photoreceptors and signal processing neurons. Different regions in the retina display unique susceptibility to pathology, with many retinal diseases primarily affecting the macula.ObjectivesTo better understand the properties of different retinal areas we studied the differential distribution of metabolites across the retina.MethodsWe conducted an untargeted metabolomics analysis on full-thickness punches from three different regions (macula, temporal peri-macula and periphery) of healthy primate retina.ResultsNearly half of all metabolites identified showed differential abundance in at least one comparison between the three regions. Furthermore, mapping metabolomics results from macula-specific eye diseases onto our region-specific metabolite distributions revealed differential abundance defining systemic metabolic dysregulations that were region specific.ConclusionsThe unique metabolic phenotype of different retinal regions is likely due to the differential distribution of different cell types in these regions reflecting the specific metabolic requirements of each cell type. Our results may help to better understand the pathobiology of retinal diseases with region specificity.

Object Image Size Is a Fundamental Coding Dimension in Human Vision: New Insights and Model

In previous psychophysical work we found that luminance contrast is integrated over retinal area subject to contrast gain control. If different mechanisms perform this operation for a range of superimposed retinal regions of different sizes, this could provide the basis for size-coding. To test this idea we included two novel features in a standard adaptation paradigm to discount more pedestrian accounts of repulsive size-aftereffects. First, we used spatially jittering luminance-contrast adaptors to avoid simple contour displacement aftereffects. Second, we decoupled adaptor and target spatial frequency to avoid the well-known spatial frequency shift aftereffect. Empirical results indicated strong evidence of a bidirectional size adaptation aftereffect. We show that the textbook population model is inappropriate for our results, and develop our existing model of contrast perception to include multiple size mechanisms with divisive surround-suppression from the largest mechanism. For a given stimulus patch, this delivers a blurred step-function of responses across the population, with contrast and size encoded by the height and lateral position of the step. Unlike for textbook population coding schemes, our human results (N = 4 male, N = 4 female) displayed two asymmetries: (i) size aftereffects were greatest for targets smaller than the adaptor, and (ii) on that side of the function, results did not return to baseline, even when targets were 25% of adaptor diameter. Our results and emergent model properties provide evidence for a novel dimension of visual coding (size) and a novel strategy for that coding, consistent with previous results on contrast detection and discrimination for various stimulus sizes.

Prevalence of venous loops and association with retinal ischemia in diabetic retinopathy using widefield swept-source OCT angiography.

To investigate the prevalence and clinical characteristics of diabetic patients with retinal venous loops (RVLs) and to assess the association with retinal ischemia using widefield swept-source optical coherence tomography angiography (WF SS-OCTA). In this retrospective, cross-sectional study, a total of 195 eyes of 132 diabetic patients (31 eyes with no diabetic retinopathy (DR), 76 eyes with nonproliferative DR (NPDR), and 88 eyes with proliferative DR (PDR)) were imaged with WF SS-OCTA using Angio 6 × 6mm and Montage 15 × 15mm scans. Quantitative ischemia-related parameters, including ischemia index (ratio of nonperfusion area to total retinal area), foveal avascular zone (FAZ), and neovascularization features, were evaluated. RVLs were classified as type I or type II according to the branching level of the feeder vessel. A multivariate generalized estimating equations (GEE) logistic regression model was used to analyze the association of systemic parameters and ischemia-related metrics with RVLs in PDR eyes. Forty-eight RVLs were identified in 22 eyes (11.28%). The prevalence of RVLs was higher in PDR compared to NPDR eyes (21.59% vs. 3.95%, P < 0.05). Type II RVLs accounted for a higher proportion than type I (89.58% vs. 10.42%, P < 0.001). RVLs were more likely to originate from superior (vs. inferior) and temporal (vs. nasal) veins (P < 0.05). The GEE model showed that neovascularization (NV) flow area and diastolic blood pressure were associated with RVLs in the PDR group (P < 0.05). WF SS-OCTA is useful for the identification of RVLs in patients with DR. NV flow area and diastolic blood pressure were associated with the presence of RVLs in eyes with PDR. Ischemia index, FAZ, and other WF SS-OCTA parameters were not associated with RVLs. Further longitudinal studies are needed to identify the role of RVLs in DR progression.