Retinal Plexus Research Articles

Plexus‐specific analysis of retinal neurovascular coupling using optical coherence tomography angiography

AbstractPurposeTo analyse retinal neurovascular coupling (NVC) in a plexus‐specific manner at baseline and during flicker light stimulation using optical coherence tomography angiography (OCTA) and to thereby use the retina as a model for non‐invasive microvascular assessment of NVC in humans.Methods22 healthy subjects were included in the study. Macular 10°x10° volume scans were acquired at baseline and during flicker light stimulation using the Spectralis OCTA module (Heidelberg Engineering, Heidelberg, Germany). Vessel densities (VDs) in the superficial (SCP), intermediate (ICP) and deep capillary plexus (DCP) as well as in the full retina (FR) were assessed after thresholding the respective slabs by mean values. Large vessels and resulting projection artefacts were removed using a threshold‐based approach. Capillary representation was optimized using a “Frangi filter”. Volumetric blood flow and vessel diameters were measured using a Doppler‐OCT prototype.ResultsFlicker light stimulation induced a significant FR VD increase from 39.7 ± 1.7 to 41.2 ± 1.6% (+3.8 ± 2.7%; p < 0.001). Upon separate analysis of the three retinal plexus, VD significantly increased by +9.9 ± 6.7% in SCP, by ±6.6 ± 1.7% in ICP and by +4.9 ± 2.3% in DCP (p<0.001 for all three). This increase was significantly higher in SCP than in ICP (p = 0.02) and DCP (p = 0.002). Arterial diameters increased by +3.7 ± 3.1% (p < 0.001), venous diameters rose by +4.5 ± 3.0% (p<0.001). Volumetric blood flow increased by +39.9±34.9% (p<0.001) in arteries and by +29.8 ± 16.8% (p < 0.001) in veins.ConclusionsIn summary, a robust increase of retinal VD which was most pronounced in SCP could be observed upon flicker light stimulation. These data propose a plexus‐specific mechanism, to precisely meet the metabolic needs of retinal cells. The location of SCP in the inner retinal layers, where increase of metabolic demands is suggested to be greatest during flicker light stimulation, could be explanatory for the locally bigger response.

Macular and choroidal perfusion using optical coherence tomography angiography in type-2 diabetic patients without diabetic retinopathy

Purpose The aim of this study was to evaluate the changes in retinal vascular plexuses and choriocapillaris in type-2 diabetes mellitus (DM) patients without clinical diabetic retinopathy (DR) and to compare them with healthy controls and to identify early preclinical biomarkers for DR using optical coherence tomography angiography (OCTA). Patients and methods This is a prospective cross-sectional study that included 68 eyes (34 eyes of type-2 diabetic patients without DR and 34 eyes of healthy controls). Using OCTA, the vessel density (VD) in the superficial and deep capillary plexuses, macular thickness, foveal avascular zone (FAZ) area, and choriocapillaris flow area were measured. The OCTA morphological findings in diabetic patients were noted. In addition, the correlations between OCTA and glycosylated hemoglobin and diabetes duration were evaluated. Results There was a statistically significant decrease in the parafoveal macular thickness in the diabetic group compared with the control group (the superior–hemi parafoveal thickness was 310.94±10.84 vs. 321.71±11.2 μm, respectively, P=0.001, while the inferior–hemi parafoveal thickness was 304.71±11.04 vs. 320.82±11.25 μm, respectively, P=0.001). There was no statistically significant difference in the parafoveal and perifoveal superficial capillary plexus and DCP VD in the diabetic patients compared with the controls. In addition, there was no change in the FAZ area between the two groups, but there was a significant difference regarding the FAZ irregularity (P=0.00). Microaneurysms (100%), capillary nonperfusion (94%), capillary loop (17.6%), enlarged perifoveal intercapillary spaces (17.6%), punched-out FAZ (12%), lost spider web (6%), and capillary blind end (6%) were detected in the diabetic patients. A negative significant correlation was found between the parafoveal thickness and glycosylated hemoglobin in the DM group in the inferior–hemi thickness (r=−0.61, P=0.01), and between DM duration and VD in the DCP in the parafoveal and perifoveal areas (r=−0.55, P=0.06 and r=0.62, P=0.018, respectively). Conclusion OCTA can be used to diagnose preclinical maculopathy/retinopathy in diabetic patients using the parafoveal retinal thickness, DCP VD, FAZ irregularities, quantification of microaneurysms, and choriocapillaris flow area as biomarkers.

Pharmacokinetic comparison of four major bio-active components of naoxintong capsule in normal and acute blood stasis rats using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry

Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule (NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline hydrochloride twice; during the two subcutaneous injections, the rats were placed in ice water for 4 min to reproduce the model rat of acute blood stasis. The normal and acute blood stasis rats were administrated a 5.04 g/kg dose of NXTC suspension. Then, blood samples were collected from the posterior retinal venous plexus at different time points. Plasma concentrations of four major bio-active components including caffeic acid, ferulic acid, formononetin, and tanshinone IIA in NXTC were measured using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry. Phoenix WinNonlin v6.2 software was used to calculate the pharmacokinetic parameters. Results: Compared with the normal rats, the acute blood stasis rats showed a significant decrease in Cmax of ferulic acid and formononetin, AUCall of caffeic acid and ferulic acid, and AUCINF_obs of ferulic acid. Conversely, an increase in the Vz_F_obs and MRTlast of ferulic acid and caffeic acid was observed. These findings demonstrate that the absorption of the four NXTC components was weakened in the acute blood stasis rats and that the elimination time was prolonged. Conclusions: The significant difference in some parameters of the four NXTC components between the normal and acute blood stasis rats might be caused by an increase in blood viscosity and the subsequent slowing down of blood flow in the acute blood stasis rats. The pharmacokinetic study conducted in pathological state can provide important information and scientific basis for further rational clinical application of NXTC.

Pharmacokinetic comparison of four major bio-active components of naoxintong capsule in normal and acute blood stasis rats using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry

Objective: To compare the pharmacokinetic differences of the main components of Naoxintong capsule (NXTC) in normal and acute blood stasis rats. Materials and Methods: Rats were subcutaneously injected with adrenaline hydrochloride twice; during the two subcutaneous injections, the rats were placed in ice water for 4 min to reproduce the model rat of acute blood stasis. The normal and acute blood stasis rats were administrated a 5.04 g/kg dose of NXTC suspension. Then, blood samples were collected from the posterior retinal venous plexus at different time points. Plasma concentrations of four major bio-active components including caffeic acid, ferulic acid, formononetin, and tanshinone IIA in NXTC were measured using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry. Phoenix WinNonlin v6.2 software was used to calculate the pharmacokinetic parameters. Results: Compared with the normal rats, the acute blood stasis rats showed a significant decrease in Cmax of ferulic acid and formononetin, AUCall of caffeic acid and ferulic acid, and AUCINF_obs of ferulic acid. Conversely, an increase in the Vz_F_obs and MRTlast of ferulic acid and caffeic acid was observed. These findings demonstrate that the absorption of the four NXTC components was weakened in the acute blood stasis rats and that the elimination time was prolonged. Conclusions: The significant difference in some parameters of the four NXTC components between the normal and acute blood stasis rats might be caused by an increase in blood viscosity and the subsequent slowing down of blood flow in the acute blood stasis rats. The pharmacokinetic study conducted in pathological state can provide important information and scientific basis for further rational clinical application of NXTC.

Optical Coherence Tomography Angiography in Diabetic Patients: A Systematic Review.

Background: Diabetic retinopathy (DR) is the leading cause of legal blindness in the working population in developed countries. Optical coherence tomography (OCT) angiography (OCTA) has risen as an essential tool in the diagnosis and control of diabetic patients, with and without DR, allowing visualisation of the retinal and choroidal microvasculature, their qualitative and quantitative changes, the progression of vascular disease, quantification of ischaemic areas, and the detection of preclinical changes. The aim of this article is to analyse the current applications of OCTA and provide an updated overview of them in the evaluation of DR. Methods: A systematic literature search was performed in PubMed and Embase, including the keywords “OCTA” OR “OCT angiography” OR “optical coherence tomography angiography” AND “diabetes” OR “diabetes mellitus” OR “diabetic retinopathy” OR “diabetic maculopathy” OR “diabetic macular oedema” OR “diabetic macular ischaemia”. Of the 1456 studies initially identified, 107 studies were screened after duplication, and those articles that did not meet the selection criteria were removed. Finally, after looking for missing data, we included 135 studies in this review. Results: We present the common and distinctive findings in the analysed papers after the literature search including the diagnostic use of OCTA in diabetes mellitus (DM) patients. We describe previous findings in retinal vascularization, including microaneurysms, foveal avascular zone (FAZ) changes in both size and morphology, changes in vascular perfusion, the appearance of retinal microvascular abnormalities or new vessels, and diabetic macular oedema (DME) and the use of deep learning technology applied to this disease. Conclusion: OCTA findings enable the diagnosis and follow-up of DM patients, including those with no detectable lesions with other devices. The evaluation of retinal and choroidal plexuses using OCTA is a fundamental tool for the diagnosis and prognosis of DR.

Assessment of the degree of restoration of the retinal structure and chorioretinal blood flow after surgical treatment of large-diameter macular holes

The aim: to evaluate the restoration features of the structural relationships of the retina and chorioretinal blood fl ow after surgical treatment of large-diameter macular hole (MH) using a modifi ed technology.Material and methods. A prospective study of 14 patients (14 eyes), 13 women and 1 man, with medium-and large-diameter MH was conducted. The mean age of the patients was 67.7 ± 5.38 (55–80) years. The study included patients with endto-end MH of the 3rd–4th stage according to the classifi cation of J. Gass. All patients underwent surgical treatment of macular rupture according to the proposed method of inverted fl ap of the internal limiting membrane (ILM) and fi lling it into a “pocket” formed between the retina and the ILM.Optical coherence tomography (OCT) was performed along with traditional research methods. The obtained images were used to measure manually the parameters of retinal MH, the thickness of the choroid in the projection of the rupture and the fovea zone before the operation and 1, 3 and 6 months after the operation. In the angio-mode, the foveal avascular zone (FAZ) was evaluated, as well as the density of capillaries of the superfi cial and deep retinal plexus in four quadrants, with the exception of the central zone.Results. In all patients, it was possible to achieve MH blocking. Visual acuity in the eyes with MH varied from 0.02 to 0.3, while in the comparison group, the best corrected visual acuity was from 0.3 to 1.0 (p = 0.002). An increase in the diameter of large choroidal vessels, as well as a pronounced decrease in the diameter of the posterior short ciliary artery, attracted attention. However, despite the improvement in visual acuity, patients retained a signifi cant expansion of the FAZ, which by 6 months exceeded the FAZ area of the paired eye by 25.8 % (p = 0.01).Conclusion. The results obtained indicate that the achievement of an anatomicalreconstructive effect and even a moderate improvement in visual acuity during surgical treatment of macular holes by the modifi ed inverted flap technology of the internal limiting membrane does not determine the restoration of retinal perfusion in full.

Ly6c as a New Marker of Mouse Blood Vessels: Qualitative and Quantitative Analyses on Intact and Ischemic Retinas.

Ly6c is an antigen commonly used to differentiate between classical and non-classical monocytes/macrophages. Here we show its potential as a marker of the mouse vasculature, particularly of the retinal vascular plexuses. Ly6c was immunodetected in several tissues of C57BL/6 mice using isolectin IB4 as the control of vasculature staining. In the retina, Ly6c expression was analyzed qualitatively and quantitatively in intact, ischemic, and contralateral retinas from 0 to 30 days after the insult. Ly6c expression was observed in all organs and tissues tested, with a brighter signal and more homogeneous staining than the IB4. In the retinas, Ly6c was well expressed, allowing a detailed study of their anatomy. The three retinal plexuses were morphologically different, and from the superficial to the deep one occupied 15 ± 2, 24 ± 7, and 38 ± 1.4 percent of the retinal surface, respectively. In the injured retinas, there was extravasation of the classically activated monocyte/macrophages (Ly6chigh) and the formation of new vessels in the superficial plexus, increasing the area occupied by it to 25 ± 1%. In the contralateral retinas, the superficial plexus area decreased gradually, reaching significance at 30 days, and Ly6c expression progressively disappeared in the intermediate and deep plexuses. Although the role of Ly6c in vascular endothelial cell function is still not completely understood, we demonstrate here that Ly6c can be used as a new specific marker of the mouse vasculature and to assess, qualitatively and quantitatively, vascular changes in health and disease.

Analysis of Microvasculature in Nonhuman Primate Macula With Acute Elevated Intraocular Pressure Using Optical Coherence Tomography Angiography.

PurposeTo investigate responses of macular capillary vessel area density (VAD) of superficial and deep retinal vascular plexuses to elevations in intraocular pressure (IOP) in cynomolgus macaque monkeys using optical coherence tomography angiography (OCTA).MethodsIn five general anesthetized male cynomolgus monkeys, the IOP was increased incrementally by 10 mmHg from baseline (10 mmHg) to 70 mmHg and then decreased back to 10 mmHg (recovery state). Structural OCT (30° × 30°) and OCTA (20° × 15°) centered on the macula were obtained at each IOP and 3, 15, and 30 minutes after recovery. En face images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were extracted, and VAD (%) compared with that at baseline was calculated.ResultsThe VADs in the SVC and DVC at baseline and at 30 mmHg IOP were 34.96%, 34.15%, 35.38%, and 30.12%, respectively. The VAD plateaued until 30 mmHg; however, the VAD was affected more in the DVC than in the SVC (P = 0.008) at 30 mmHg. It showed a significant reduction at 40 mmHg (16.52% SVC, P = 0.006; 18.59% DVC, P = 0.012). In the recovery state, the SVC showed full retention of baseline VAD, but the DVC maintained VAD approximately 70% of that at baseline. Structural OCT showed hyperreflectivity in the nuclear layer, retinal swelling, and an undifferentiated ellipsoid zone from 50 mmHg.ConclusionsDespite physiological autoregulation, perifoveal microcirculation was affected at high IOP ≥ 40 mmHg, especially in the DVC, which explains the pathological mechanism of macular vulnerability in ischemic diseases.

Characterization of the Canine Retinal Vasculature With Optical Coherence Tomography Angiography: Comparisons With Histology and Fluorescein Angiography.

Purpose: To present a methodology for quantification of the canine retinal vasculature imaged by optical coherence tomography angiography (OCTA) and validate this approach by comparison with fluorescein angiography (FA) and confocal imaging of retinal wholemounts labelled by immunohistochemistry (IHC).Methods: Six normal adult dogs underwent retinal OCTA imaging in both eyes. The images extracted from the different microvascular plexuses at eight retinal locations spanning the central and mid-peripheral fundus were analyzed using the AngioTool software. FA was performed in one eye and was compared to the OCTA images. Six eyes from three dogs were processed by IHC to examine the retinal vasculature.Results: A total of four retinal plexuses were identified by OCTA in the canine retina, and their density and topographical pattern varied with eccentricity. OCTA offered improved resolution over FA with the advantage of allowing imaging of the individual plexuses. Detection by OCTA of small vessels within the deep capillary plexus was possible and approached the level of resolution achieved with ex vivo imaging of the retinal vasculature by confocal microscopy/IHC. The plexuses herein described are analogous to human retinal vasculature.Conclusion: OCTA can be used to image and quantify non-invasively the vascular retinal networks of the canine retina. We provide normative data in eight different retinal locations that can be imaged non-invasively with this technology. This could support analysis of retinal vascular changes associated with disease and following therapeutic intervention.

Age dependence of retinal vascular plexus attenuation in the triple transgenic mouse model of Alzheimer's disease

The influence of Alzheimer's disease (AD) progression and severity on the structural and functional integrity of the cerebral vasculature is well recognized. The retina is an extension of the brain; thus, changes in retinal vascular features may serve as markers of AD cerebrovascular pathologies. However, differentiating normal aging-versus AD-induced retinal vascular changes is unresolved. Therefore, we compared and quantified changes in superficial (SVP), intermediate (IVP), and deep (DVP) retinal vascular plexuses in young, middle-age, and old triple transgenic mouse model of AD (3xT-AD) to the changes that occur in age-matched controls (C57BL/6j). We used immunostaining combined with a novel tissue optical clearing approach along with a computational tool for quantitative analysis of vascular network alterations (vessel length and density) in SVP, IVP, and DVP. All three layers had comparable structural features and densities in young 3xTg-AD and control animals. In controls, IVP and DVP densities decreased with aging (−14% to −32% change from young to old, p < 0.05), while no changes were observed in SVP. In contrast, vascular parameters in the transgenic group decreased in all three layers with aging (−12% to −49% change from young to old, p < 0.05). Furthermore, in the old group, SVP and DVP vascular parameters were lower in the transgenics compared to age-matched controls (p < 0.05). Our analysis demonstrates that normal aging and progression of AD lead to various degrees of vascular alterations in the retina. Specifically, compared to normal aging, changes in vascular features of SVP and DVP regions of the retina are accelerated during AD progression. Considering recent advances in the field of depth-resolved imaging of retinal capillary network and microangiography, noninvasive quantitative monitoring of changes in retinal vascular network parameters of SVP and DVP may serve as markers for diagnosis and staging of Alzheimer's disease and discriminating AD-induced vascular attenuation from age-related vasculopathy.

Assessment of the microvasculature in poppers maculopathy

PurposeTo investigate a possible microvascular component of poppers maculopathy (PMP) using optical coherence tomography angiography (OCTA).MethodsTwelve patients suffering from poppers maculopathy were included. Health records, optical coherence tomography (OCT), and OCTA data was gathered and compared to a healthy control group (HC). PMP lesion type was determined by manifestation in OCT. OCTA-based evaluation of retinal vascular plexus and choriocapillaris (CC) was executed. Vessel density (VD) and vessel length density (VLD) in superficial and deep capillary plexus (SCP, DCP), as well as flow deficits (FD), within the foveal avascular zone (FAZ) in CC were assessed.ResultsMedian age of PMP patients was 40 (min 24; max 64) years, all male. Eleven patients presented with ellipsoid zone-type lesions; one patient showed a vitelliform-type lesion. No qualitative microvascular changes between PMP patients and HC were identified. Quantitative values for VD and VLD of SCP and DCP did not differ in between the two groups. The analysis of FDs in CC showed no deviation from PMP patients to HC.ConclusionsNo vascular anomalies in qualitative and quantitative analysis in OCTA were detected in PMP patients. The constitution of the CC within FAZ of PMP patients does not differ from HC when assessed as FD.

Posterior segment manifestations and imaging features post-COVID-19.

To report the posterior segment (uvea and retinal) manifestations and imaging characteristics of eyes of patients with and after coronavirus disease 2019 (COVID-19). We searched the PubMed/MEDLINE database to identify relevant articles using the following search terms: COVID-19, SARS-CoV-2, retina, uvea, optic nerve, retinal findings, posterior segment manifestations, and endophthalmitis. Articles published from December 1, 2019, to May 30, 2021, and indexed in PubMed/ MEDLINE were screened. For the purpose of this review, we included clinical features of 26 case reports and 8 case series. The posterior segment manifestations reported included cotton wool spots, retinal hemorrhages, central serous retinopathy, papillophlebitis, optic neuritis, panuveitis, multifocal retinitis, necrotizing retinitis, central retinal artery/vein occlusion, and Purtschner like retinopathy. In this review, we have also included optical coherence tomography angiography (OCTA) features that have been described in COVID-19 patients with pneumonia. COVID-19 patients can experience uveo-retinal manifestations even after recovery. These patients, even if asymptomatic for eye symptoms, should undergo an eye evaluation to rule out posterior segment involvement. OCTA performed in these patients revealed microvascular changes in the superficial and deep retinal plexuses. Some of these patients may require anticoagulant or antiplatelet therapy.

Optical coherence tomography-angiography in diabetic retinopathy diagnosis and monitoring

Optical coherence tomography-angiography is a modern noninvasive method of 3D imaging and quantitative analysis of the retinal and choroidal microvasculature. It allows detecting manifestation and progression of diabetic retinopathy, planning treatment and evaluating its results.Optical coherence tomography angiography expands our understanding of microvascular changes in retinal vascular plexuses at different disease stages and deepens the understanding of its pathogenesis.

The effect of AAV-mediated downregulation of Claudin-3 on the development of mouse retinal vasculature

Retinal vascular development is a very tightly regulated and organized process of vessel formation and regression to generate the mature vasculature system. Claudin-3 has been found to be required for the normal development of the neural retina and its vessels in zebrafish in our recent study. In this study, we investigated whether Claudin-3 played a role in the development of mouse retinal vasculature. Immunofluorescent staining was performed to detect the expression and localization of Claudin-3 in the mouse retina. Intravitreal injection of a recombinant adeno-associated virus (AAV) expressing a short hairpin RNA targeting Claudin-3 mRNA was performed to down-regulate Claudin-3 expression in retina in neonatal (Postnatal Day 3, P3) C57BL/6J mice. Retinal vessels were examined by isolectin B4 immunofluorescent staining on the whole-mount retinas and frozen retinal sections at P10. The apoptotic retinal ganglion cells (RGCs) were measured by TdT-mediated dUTP nick-end labelling (TUNEL) staining. Vascular endothelial growth factor A (VEGF-A) expression was detected by immunofluorescent staining. The protein levels of Claudin-3, VEGF-A and B cell lymphoma 2 (Bcl-2) were evaluated by Western blot at P7, P10 and P14. We found that Claudin-3 mainly expressed in the RGCs and progressively increased during the retinal development. The AAV-mediated downregulation of Claudin-3 at P3 impeded the development of retinal deep vascularization of P10 mouse, but without effect on the development of the retinal superficial plexus. Claudin-3 knockdown increased RGC apoptosis and reduced the expression of VEGF-A and Bcl-2 in the retinas. These results suggested that the downregulation of Claudin-3 induced RGC apoptosis and impeded the mouse retinal vascular development by downregulating the levels of VEGF-A and Bcl-2.

OCT-Angiography Findings in Patients with Amblyopia: Comparison between Healthy Controls, Treatment-Responsive, and Treatment-Unresponsive Amblyopic Patients.

There is no consensus on whether amblyopia affects the retinal vascular plexus and morphology. Previous studies focused on the differences between amblyopic patients and normal controls without evaluating amblyopic eyes after patching. To evaluate differences in the superficial vascular density of amblyopic eyes, normal eyes, and amblyopic eyes reaching normal BCVA after patch therapy, OCTA was used. All patients underwent a comprehensive ophthalmological examination, including visual acuity, refraction, ocular motility tests, and anterior and posterior segment examination. OCTA was performed by an expert physician using the Zeiss Cirrus 5000-HD-OCT Angioplex (Carl Zeiss, Meditec, Inc., Dublin, OH, USA). OCTA scans were performed using a 3 × 3 mm2 and 6 × 6 mm2 fovea-centered image setting. The mean outer macular vessel density in the previously amblyopic group was 19.15 ± 0.51%. This was statistically significantly higher than in both the amblyopic group (18.70 ± 1.14%) and the normal controls (18.18 ± 1.40%) (p = 0.014). The previously amblyopic group also significantly differed from both normal controls and amblyopic eyes with regards to the inner (p = 0.011), outer (p = 0.006), and full (p = 0.003) macular perfusion. Finally, linear regression analysis revealed that BCVA was linearly correlated to outer perfusion in amblyopic (p = 0.003) and ex amblyopic eyes (p < 0.001). Considering the cross-sectional nature of our study, from our results, we can only hypothesize a possible correlation between light stimulation and retinal vasculature development. However, further longitudinal studies are needed to support this hypothesis.

Optical coherence tomography angiography in amblyopia: A critical update on current understandings and future perspectives.

Optical coherence tomography angiography (OCTA) is a non-invasive tool to assess the retino-choroidal vasculature in vivo. It tracks the red blood cell movement and maps the vasculature in quick succession. In routine, diabetic retinopathy, age related macular degeneration, central serous chorioretinopathy, and others are commonly being studied to unveil its clinic role. On the other hand, amblyopia is a condition where the visual acuity is subnormal due to non-organic causes in the eye. But the OCTA studies till now have shown variable changes along retino-choroidal vasculature. Hence, to comprehend the existing literature knowledge, a systematic literature search was carried out and the original works describing novel findings in amblyopic eyes on OCTA were included. Upon detailed assessment, firstly, the disturbed vasculature along superficial retinal plexus, deeper retinal plexus, and choroidal plexus were evident in most untreated amblyopic eyes. However, such changes were not uniform, which is due to noted heterogenic patient profile, small sample size, biometric biases, non-uniform algorithms, and other factors. And to note, even in presence of such diverse changes, almost all the authors stated a plausible explanation for their notable changes. Secondly, the utility of OCTA in identifying vascular changes with standard treatments and segregation of visual beneficiaries from non-beneficiaries were possible. Hence, to conclude, OCTA is a valuable tool which can provide valuable useful insights into the amblyopic eyes during pre and post treatment periods. However, to gather more concrete evidence for clinical benefits, systematic, homogenous, and better structured clinical studies are mandated.

Specialized endothelial tip cells guide neuroretina vascularization and blood-retina-barrier formation.

Endothelial tip cells guiding tissue vascularization are primary targets for angiogenic therapies. Whether tip cells require differential signals to develop their complex branching patterns remained unknown. Here, we show that diving tip cells invading the mouse neuroretina (D-tip cells) are distinct from tip cells guiding the superficial retinal vascular plexus (S-tip cells). D-tip cells have a unique transcriptional signature, including high TGF-β signaling, and they begin to acquire blood-retina barrier properties. Endothelial deletion of TGF-β receptor I (Alk5) inhibits D-tip cell identity acquisition and deep vascular plexus formation. Loss of endothelial ALK5, but not of the canonical SMAD effectors, leads to aberrant contractile pericyte differentiation and hemorrhagic vascular malformations. Oxygen-induced retinopathy vasculature exhibits S-like tip cells, and Alk5 deletion impedes retina revascularization. Our data reveal stage-specific tip cell heterogeneity as a requirement for retinal vascular development and suggest that non-canonical-TGF-β signaling could improve retinal revascularization and neural function in ischemic retinopathy.

Change in the Foveal Avascular Zone and Macular Capillary Network Density after Hyperbaric Oxygen Therapy in Healthy Retina.

PurposeThis study aimed to evaluate responses in retinal tissue by swept source OCT angiography (OCT-A) to hyperoxia after hyperbaric oxygen (HBO2) therapy.Methods The study was conducted in volunteers who received HBO2 treatment but did not have any eye disease. Patients underwent detailed eye examinations including dilated fundus examination, visual acuity, and refraction before being admitted for HBO2 therapy. Measurements were made before and immediately after HBO2 therapy. Enface images of the retinal vasculature were obtained from the superficial and deep retinal plexus (SP/DP). Quantitative analysis of the vessel density (VD) and foveal avascular zone (FAZ) area was performed.Results In total, 31 patients (15 female) with healthy retina were included in the study. The mean age was 42.8 years. The mean SP vascular density measurements before HBO2 therapy for the right and left eyes were 15.18 1.2 mm and 15.01 1.3 mm, respectively; the measurements after HBO2 therapy for the right and left eyes were 14.34 1.4 mm and 14.48 1.19 mm. The mean DP vascular density measurements before HBO2 therapy for the right and left eyes were 16.03 1.69 mm and 16.1 1.45 mm, respectively; the measurements after HBO2 therapy for the right and left eyes were 15.02 1.65 mm and 15.12 2.16 mm, respectively. Reduction of mean VD in superficial and deep plexus after HBO2 was statistically significant (P = 0.001 and P = 0.000, respectively). Changes in mean FAZ area before and after HBO2 therapy were not statistically significant (P = 0.719).Conclusion The healthy retina responds to oxygen supersaturation with HBO2 therapy by eventually decreasing vascular density in all layers. These findings may be important for further studies especially related to retina and choroidal oxygenation.

Retinal OCT Findings in Patients after COVID Infection

Purpose: The aim of this study was to assess and compare the optic nerve, retina, and retinal vessel parameters in recovered COVID-19 patients and healthy patients by using optical coherence tomography angiography (OCT-a). Methods: In all, 156 eyes of post-COVID-19 patients and 98 eyes of subjects from a control group were enrolled in our study. BCVA, intra ocular pressure (IOP) measurement, fundus examination, and OCT images, including macular cube, OCT-RNFL, and angio-OCT 6 × 6 mm examinations, were performed for both groups. The measurements were acquired using Swept Source OCT DRI OCT Triton. In the post-COVID-19 group, 762 OCT protocols were obtained. For statistical analysis, parameters from only one eye from each subject were taken. Results: In the measured parameters, no significant differences were observed, i.e., central macular thickness (p = 0.249); RNFL (p = 0.104); FAZ (p = 0.63); and vessel density of superficial retinal vascular plexus in central (p = 0.799), superior (p = 0.767), inferior (p = 0.526), nasal (p = 0.402), and temporal (p = 0.582) quadrants. Furthermore, a slit-lamp examination did not reveal any COVID-19-related abnormalities. Conclusion: OCT examination did not detect any significant changes in morphology or morphometry of the optic nerve, retina, or the retina vessels due to COVID-19.

Optical coherence tomography angiography in the multimodal assessment of the retinal posterior pole in autosomal dominant optic atrophy.

To assess retinal vascular involvement in patients with autosomal dominant optic atrophy (ADOA) genetically confirmed by the presence of the OPA1 (Optic Atrophy 1) gene mutation using a multimodal protocol of investigation of retinal posterior pole. In this cross-sectional, case-control, observational study, both eyes of 13 patients with a genetic diagnosis of ADOA were compared with both eyes of 13 healthy controls (HCs). All subjects underwent full ophthalmological examination, spectral domain-optical coherence tomography (SD-OCT), fundus perimetry (FP) and OCT angiography (OCTA). Vessel density (VD) of the superficial and deep macular vascular plexi and of the radial peripapillary capillary plexus were significantly decreased (p ≤ 0.001) in ADOA patients compared with HCs. The area under the receiver operating characteristics analysis also revealed high values of sensitivity and specificity of OCTA parameters in distinguish between patients and HCs. A strong correlation (Pearson Coefficient, r = 0.91) emerged between OCTA VD of the superficial retinal plexus and the average Ganglion Cell Layer (GCL) thickness as measured by SD-OCT; a slightly lower correlation (Pearson Coefficient, r = 0.89) was also found between VD of the deep plexus and the average GCL thickness of the same eyes in patients with ADOA. The correlation among values of differential light sensitivity (DLS) measured by FP with VD and GCL thickness parameters was also investigated. The correlation analysis among DLS and the VD parameters showed from low-to-moderate correlation (ranging from r = 0.29 for the deep fovea VD to r = 0.59 for the deep whole image VD). The correlation coefficient between the mean DLS and the average thickness of GCL was more significant (Pearson Coefficient, r = 0.75). A significant correlation emerged also between the VD and the visual acuity, in terms of LogMAR BCVA (best-corrected visual acuity), especially for the VD of the deep capillary plexus (Pearson Coefficient for the Deep whole Image VD and LogMAR BCVA r = -0.75; for the Deep parafovea VD and LogMAR BCVA r = -0.78). Retinal microvascular assessment by OCTA angiography can provide relevant clinical information on retinal involvement in ADOA patients. In patients with genetically confirmed OPA1-related ADOA, there is a decrease in retinal vessel density associated with GCL thinning and DLS reduction.