Retinal Vascularization Research Articles

Molecular and Cellular Mechanisms Involved in the Pathophysiology of Retinal Vascular Disease-Interplay Between Inflammation and Oxidative Stress.

Retinal vascular diseases encompass several retinal disorders, including diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, and retinal vascular occlusion; these disorders are classified as similar groups of disorders due to impaired retinal vascularization. The aim of this review is to address the main signaling pathways involved in the pathogenesis of retinal vascular diseases and to identify crucial molecules and the importance of their interactions. Vascular endothelial growth factor (VEGF) is recognized as a crucial and central molecule in abnormal neovascularization and a key phenomenon in retinal vascular occlusion; thus, anti-VEGF therapy is now the most successful form of treatment for these disorders. Interaction between angiopoietin 2 and the Tie2 receptor results in aberrant Tie2 signaling, resulting in loss of pericytes, neovascularization, and inflammation. Notch signaling and hypoxia-inducible factors in ischemic conditions induce pathological neovascularization and disruption of the blood-retina barrier. An increase in the pro-inflammatory cytokines-TNF-α, IL-1β, and IL-6-and activation of microglia create a persistent inflammatory milieu that promotes breakage of the blood-retinal barrier and neovascularization. Toll-like receptor signaling and nuclear factor-kappa B are important factors in the dysregulation of the immune response in retinal vascular diseases. Increased production of reactive oxygen species and oxidative damage follow inflammation and together create a vicious cycle because each factor amplifies the other. Understanding the complex interplay among various signaling pathways, signaling cascades, and molecules enables the development of new and more successful therapeutic options.

Bax expression impacts postnatal retinal vascular development and hyperoxia sensitivity

Apoptosis plays prominent roles during organ development, maturation and homeostasis. In the retina, Bcl-2 family members function through the intrinsic cell death pathway with vital roles during vascular development and hyperoxia-mediated vessel obliteration during oxygen induced ischemic retinopathy (OIR). Bim, a BH3 only protein Bcl-2 family member, binds and activates Bax and/or Bak to facilitate apoptosis. In some systems deletion of both Bax and Bak are required to prevent cell loss, such as regression of ocular hyaloid vasculature. We previously showed Bim expression significantly impacts normal retinal vascular development and sensitivity to hyperoxia. Mice deficient in Bim (Bim-/-) show increased retinal vascular density and are protected from hyperoxia mediated vessel obliteration. Since Bim activates Bax, here we determined the impact lack of Bax expression has on these processes. Compared to Bax+/+ mice, retinas from Bax-/- mice had significantly increased numbers of retinal endothelial cells and pericytes. We also demonstrated that hyperoxia-mediated vessel obliteration during OIR was significantly decreased in the absence of Bax. Although the increased endothelial cell numbers were comparable to that of Bim-/- mice, the increased numbers of pericytes were not to the extent noted in Bim-/- mice. These changes were supported by partial protection of retinal vessels from hyperoxia in Bax-/- mice compared to that noted in Bim-/- mice. Thus, Bim-Bax driven pathway is sufficient to remove excess endothelial cells but not pericytes during postnatal retinal vascularization and hyperoxia-mediated vessel obliteration. Thus, additional Bim-mediated pathway(s) are required for removal of pericytes and hyperoxia-mediated vessel obliteration.

Retinal neurovascular assessment and choroidal vascularity index in patients with keratoconus

This study aims to evaluate the macular and the optic nerve head thickness and vascular profiles in KC patients and compare them with two groups of healthy emmetrope and subjects with myopic-astigmatism. This cross-sectional study was conducted at Khatam-Al-Anbia Eye Hospital between 2022 and 2023. Subjects aged 18 to 40 were prone to be included in the study. The participants in this study were grouped into three categories: emmetrope (E), myopic-astigmatic (MA), and keratoconus (KC). All participants underwent a comprehensive ocular examination, as well as macular and optic nerve head (ONH) optical coherence tomography angiography (OCTA). In this study, 143 subjects, 50 cases in the KCN group, 46 cases in the E group, and 47 cases in the MA group, enrolled. There was no difference between the three groups regarding age (p = 0.123) and gender (p = 0.632). The superficial and deep capillary densities at the fovea, parafovea, and perifovea were significantly lower in KC patients than in the control groups (p < 0.01). The radial peripapillary capillary (RPC)- all vessels’ density is significantly lower in the KC group (p < 0.001). Besides, the choroidal vascularity index (CVI) and choroidal luminal area (CLA) were considerably higher in KC patients (p < 0.001). The macular and ONH vascular profile in KC patients significantly differs from the vascular profile of healthy controls. Further scientific evidence regarding the systemic implications of keratoconus on the vascular system would be desirable to understand the connections between KC and vascular disease.

Vitreoretinal Surgery in Familial Exudative Vitreoretinopathy

Familial exudative retinopathy(FEVR) is a hereditary vitreoretinal disorder characterized by anomalous retinal angiogenesis. Incomplete peripheral retinal vascularization and subsequent retinal ischemia are the hallmark features of FEVR, which can cause various types of retinal detachment. The development of retinal detachment is %21-64 of the cases. The aim of this study is to summarize the treatment methods applied to different types of detachments occuring in FEVR.

RNA binding protein ELAVL1-mediated USP33 stabilizes HIF1A to promote pathological proliferation, migration and angiogenesis of RECs.

Dysfunction of retinal vascularization plays pathogenic roles in retinopathy of prematurity (ROP). Hypoxia-inducible factor 1 alpha (HIF1A) is activated by hypoxia and contributes to ROP progression. Herein, we clarified the mechanism underlying HIF1A activation in human retinal vascular endothelial cells (HRECs) under hypoxia. Protein expression was assayed by immunoblot analysis. Cell migration, microtubule formation, invasion, proliferation, and viability were detected by wound-healing, tube formation, transwell, EdU, and CCK-8 assays, respectively. Bioinformatics was used to predict the deubiquitinase-HIF1A interactions and RNA binding proteins (RBPs) bound to USP33. The impact of USP33 on HIF1A deubiquitination was validated by immunoprecipitation (IP) assay. RNA stability analysis was performed with actinomycin D (Act D) treatment. The ELAVL1/USP33 interaction was assessed by RNA immunoprecipitation experiment. In hypoxia-exposed HRECs, HIF1A and USP33 protein levels were upregulated. Deficiency of HIF1A or USP33 suppressed cell migration, proliferation and microtubule formation of hypoxia-exposed HRECs. Mechanistically, USP33 deficiency led to an elevation in HIF1A ubiquitination and degradation. USP33 deficiency reduced HIF1A protein levels to suppress the proliferation and microtubule formation of hypoxia-induced HRECs. Moreover, the RBP ELAVL1 stabilized USP33 mRNA to increase USP33 protein levels. ELAVL1 decrease repressed the proliferation and microtubule formation of hypoxia-induced HRECs by reducing USP33. Our study identifies a novel ELAVL1/USP33/HIF1A regulatory cascade with the ability to affect hypoxia-induced pathological proliferation, angiogenesis, and migration in HRECs.

Detection of diabetic retinopathy using artificial intelligence: an exploratory systematic review

Diabetic retinopathy is a disease that can lead to vision loss and blindness in people with diabetes, so its early detection is important to prevent ocular complications. The aim of this study was to analyze the usefulness of artificial intelligence in the detection of diabetic retinopathy. For this purpose, an exploratory systematic review was performed, collecting 77 empirical articles from the Scopus, IEEE, ACM, SciELO and NIH databases. The results indicate that the most commonly used factors for the detection of diabetic retinopathy include changes in retinal vascularization, macular edema and microaneurysms. Among the most commonly applied algorithms for early detection are ResNet 101, CNN and IDx-DR. In addition, some artificial intelligence models are reported to have an accuracy ranging from 90% to 95%, although models with accuracies below 80% have also been identified. It is concluded that artificial intelligence, and in particular deep learning, has been shown to be effective in the early detection of diabetic retinopathy, facilitating timely treatment and improving clinical outcomes. However, ethical and legal concerns arise, such as privacy and security of patient data, liability in case of diagnostic errors, algorithmic bias, informed consent, and transparency in the use of artificial intelligence.

Case 333.

A 61-year-old male patient without prior history of ophthalmologic problems presented with pain and redness in the left eye associated with slowly progressive proptosis over the previous 6 months. The patient also had diplopia in rightward and downward gaze. There was no vision loss. Mild fullness was seen in the periorbital tissues without any redness or fluctuance and with no purulent discharge from the left eye. The patient was otherwise healthy, with a 6-year history of diabetes mellitus and an 8-year history of hypertension managed well with medication. There was no history of trauma to the head or face. At clinical examination, conjunctival edema and redness with proptosis were noted. The cornea was clear. Evaluation of eye movements revealed restricted motion of the left eye in medial gaze and downward gaze. Ophthalmoscopic evaluation did not show any substantial abnormality. The retina and retinal vascularity were unremarkable. The right eye was unremarkable. Uncorrected visual acuity was 20/30 in the right eye and 20/40 in the left eye. Corrected visual acuity was 20/20 in both eyes. Complete blood cell count, as well as liver and kidney function test results, were within normal limits. The erythrocyte sedimentation rate and C-reactive protein level were normal. Thyroid function test results were normal. The patient subsequently underwent CT of the orbits without and with contrast enhancement (Fig 1) followed by further evaluation with MRI of the orbits without and with contrast enhancement (Figs 2-4).

Comparison of ranibizumab and conbercept treatment in type 1 prethreshold retinopathy of prematurity in zone II

PurposeThe treatment with anti-VEGF for Retinopathy of prematurity (ROP) has already been widely applied in clinics even though there are still many concerns about this treatment. In this project we investigated the clinical outcomes of intra-vitreous conbercept (IVC) and ranibizumab (IVR) injection for treating type 1 prethreshold ROP in Zone II.MethodsThe data of ROP infants receiving IVR or IVC from January 2017 to March 2020 who were followed up for at least 12 months in our hospital was studied in the present retrospective study. Regression, reactivation, complications, and ocular biological parameters were evaluated.ResultsOne hundred twenty-five eyes (64 infants) in IVC group and 229 eyes (117 infants) in IVR group were observed in the study. All infants showed good response to the two anti-VEGF agents. No eyes deteriorated during the observation. No significant difference was found between the two groups as to the regression within one week and one month, the reactivation rate, and the retreatment interval (p > 0.05) whereas retinal complete vascularization rate at 6 mons after the initial treatment and mean completion time of retinal vascularization after initial injection showed significant difference (p < 0.05). At 12 mons PMA the ocular parameters also presented no statistical difference between the two treated groups (p > 0.05). However, the ocular showed slight myopic tendency with the anti-VEGF treatment when compared to the control group (p < 0.05) whereas there was no statistical difference revealed between the two treated groups (p > 0.05).ConclusionsBoth conbercept and ranibizumab for treating type 1 prethreshold ROP in Zone II are safe and effective. They had little effect on the development of ocular whereas there was a slight tendency of myopia after the treatment.

Characteristics of retinal vascularization in reactivated retinopathy of prematurity requiring treatment and clinical outcome after reinjection of ranibizumab

This study aimed to determine whether the state of retinal vascularization after anti-vascular endothelial growth factor (anti-VEGF) injection can help predict the risk of reactivated retinopathy of prematurity (ROP) requiring treatment and whether repeated ranibizumab injection will be effective in such cases. We retrospectively reviewed 24 infants (43 eyes) who received ranibizumab monotherapy between January 2021 and December 2022. All eyes were classified as having non-retreated ROP or retreated ROP. The state of ROP at the time of treatment, the time required for resolution of plus disease, and the extent of vascularization at 4 and 8 weeks after treatment were analyzed. Extent of temporal retinal vascularization was measured with serial fundus images using disc-fovea distance (DF) unit and disc diameter (DD). Reactivated ROP requiring treatment occurred in six infants (25.0%) and ten eyes (23.3%) after ranibizumab treatment. The mean retreatment interval was 9.0 ± 3.3 weeks (range 4–16). In the retreated ROP group, the time required for the resolution of plus disease after primary injection was longer compared to the control group (13.3 days vs 5.2 days), with a mean ROP regression time of 3.4 weeks. All eyes in the retreated ROP showed retinal vascularization < 0.5 DF from the original site at 4 weeks after injection. In 90% of cases with retreated ROP, the extent of vascularization at 8 weeks after injection was within 1 DF from the original ROP site, and all cases showed reactivation in the posterior Zone II area. The extent of retinal neovascularization in the retreated group was an average of 0.7 DD (vs 1.7 DD) and 1.3 DD (vs 3.3 DD) at 4 and 8 weeks after injection, respectively. After ranibizumab retreatment, only one reactivated case with vitreous traction progressed to focal retinal detachment, while all other cases regressed with peripheral vascular development. The continuation of delayed retinal blood vessel development after ≥ 8 weeks may indicate a high likelihood of reactivated ROP requiring treatment. In the absence of vitreous traction, ranibizumab reinjection is likely to be effective in treating reactivated ROP requiring treatment.

Comparative Phenotyping of Mice Reveals Canonical and Noncanonical Physiological Functions of TRα and TRβ.

Thyroid hormone (TH) effects are mediated through TH receptors (TRs), TRα1, TRβ1, and TRβ2. The TRs bind to the DNA and regulate expression of TH target genes (canonical signaling). In addition, they mediate activation of signaling pathways (noncanonical signaling). Whether noncanonical TR action contributes to the spectrum of TH effects is largely unknown. The aim of this study was to attribute physiological effects to the TR isoforms and their canonical and noncanonical signaling. We conducted multiparameter phenotyping in male and female TR knockout mice (TRαKO, TRβKO), mice with disrupted canonical signaling due to mutations in the TR DNA binding domain (TRαGS, TRβGS), and their wild-type littermates. Perturbations in senses, especially hearing (mainly TRβ with a lesser impact of TRα), visual acuity, retinal thickness (TRα and TRβ), and in muscle metabolism (TRα) highlighted the role of canonical TR action. Strikingly, selective abrogation of canonical TR action often had little phenotypic consequence, suggesting that noncanonical TR action sufficed to maintain the wild-type phenotype for specific effects. For instance, macrocytic anemia, reduced retinal vascularization, or increased anxiety-related behavior were only observed in TRαKO but not TRαGS mice. Noncanonical TRα action improved energy utilization and prevented hyperphagia observed in female TRαKO mice. In summary, by examining the phenotypes of TRα and TRβ knockout models alongside their DNA binding-deficient mutants and wild-type counterparts, we could establish that the noncanonical actions of TRα and TRβ play a crucial role in modulating sensory, behavioral, and metabolic functions and, thus, contribute to the spectrum of physiological TH effects.

IC100, a humanized therapeutic monoclonal anti-ASC antibody alleviates oxygen-induced retinopathy in mice

BackgroundRetinopathy of prematurity (ROP), which often presents with bronchopulmonary dysplasia (BPD), is among the most common morbidities affecting extremely premature infants and is a leading cause of severe vision impairment in children worldwide. Activations of the inflammasome cascade and microglia have been implicated in playing a role in the development of both ROP and BPD. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is pivotal in inflammasome assembly. Utilizing mouse models of both oxygen-induced retinopathy (OIR) and BPD, this study was designed to test the hypothesis that hyperoxia induces ASC speck formation, which leads to microglial activation and retinopathy, and that inhibition of ASC speck formation by a humanized monoclonal antibody, IC100, directed against ASC, will ameliorate microglial activation and abnormal retinal vascular formation.MethodsWe first tested ASC speck formation in the retina of ASC-citrine reporter mice expressing ASC fusion protein with a C-terminal citrine (fluorescent GFP isoform) using a BPD model that causes both lung and eye injury by exposing newborn mice to room air (RA) or 85% O2 from postnatal day (P) 1 to P14. The retinas were dissected on P14 and retinal flat mounts were used to detect vascular endothelium with AF-594-conjugated isolectin B4 (IB4) and citrine-tagged ASC specks. To assess the effects of IC100 on an OIR model, newborn ASC citrine reporter mice and wildtype mice (C57BL/6 J) were exposed to RA from P1 to P6, then 75% O2 from P7 to P11, and then to RA from P12 to P18. At P12 mice were randomized to the following groups: RA with placebo PBS (RA-PBS), O2 with PBS (O2-PBS), O2 + IC100 intravitreal injection (O2-IC100-IVT), and O2 + IC100 intraperitoneal injection (O2-IC100-IP). Retinal vascularization was evaluated by flat mount staining with IB4. Microglial activation was detected by immunofluorescence staining for allograft inflammatory factor 1 (AIF-1) and CD206. Retinal structure was analyzed on H&E-stained sections, and function was analyzed by pattern electroretinography (PERG). RNA-sequencing (RNA-seq) of the retinas was performed to determine the transcriptional effects of IC100 treatment in OIR.ResultsASC specks were significantly increased in the retinas by hyperoxia exposure and colocalized with the abnormal vasculature in both BPD and OIR models, and this was associated with increased microglial activation. Treatment with IC100-IVT or IC100-IP significantly reduced vaso-obliteration and intravitreal neovascularization. IC100-IVT treatment also reduced retinal microglial activation, restored retinal structure, and improved retinal function. RNA-seq showed that IC100 treatment corrected the induction of genes associated with angiogenesis, leukocyte migration, and VEGF signaling caused by O2. IC100 also corrected the suppression of genes associated with cell junction assembly, neuron projection, and neuron recognition caused by O2.ConclusionThese data demonstrate the crucial role of ASC in the pathogenesis of OIR and the efficacy of a humanized therapeutic anti-ASC antibody in treating OIR mice. Thus, this anti-ASC antibody may potentially be considered in diseases associated with oxygen stresses and retinopathy, such as ROP.

EVALUATION OF CHORIORETINAL VASCULARIZATION WITH OCT AND ANGIO-OCT IN PRIMARY ALDOSTERONISM

Objective: Primary aldosteronism (PA), the most common cause of secondary hypertension, is associated with excess cardiovascular damage and, when unilateral, is amenable to surgical cure. Our objective was to determine whether the chorioretinal microvasculature is also affected. Design and method: Ocular CT-scan (OCT) and angio-OCT images of the superficial and deep retinal plexi were obtained in PA patients at diagnosis, in wash-out from RAAS-confounding drugs (WO), and again during mineralocorticoid receptor antagonist (MRA) therapy and 4-6 months after surgical cure (PS). The images were analysed for choroidal thickness and, upon automated ImageJ processing, for indexes of total vascular area density (VAD) and length fraction (VLF), a surrogate for the number of open vessels. Results: We enrolled 11 patients with PA (51±10 yrs; 27%F); of these, 10 who had unilateral PA underwent curative surgery (p&lt;0.05 for BP, sK+ and ARR). We found that MRA therapy had no effect on any of the investigated parameters. At variance, curative surgery determined a reduction of VAD in both superficial and deep plexi (-6.4% retinal area, p=0.017 and -3.5%, p=0.023, respectively) and of VLF in the superficial plexus (-2.2%, p=0.033). Moreover, choroidal thickness (on average: -21μm, p=0.003 at 2-way ANOVA) decreased after adrenalectomy. Conclusions: OCT and angio-OCT images, which can accurately track changes in choroid- retinal vascularization, highlighted a decrease of retinal microvascular area and choroidal thickness in patients with unilateral PA, who were cured from PA.

COMBINED CENTRAL RETINAL VASCULAR OCCLUSION AS THE PRESENTING FEATURE IN β-THALASSEMIA WITH IRON DEFICIENCY ANEMIA.

To report a case of β-thalassemia trait with iron deficiency anemia presenting as a combined central retinal vein and artery occlusion. Case report. A 22-year-old woman presented with sudden-onset blurry vision in the left eye of 3-day duration. Best-corrected visual acuity was 20/20 and 20/1000 in right and left eyes, respectively. Fundus examination of the left eye revealed optic disk edema, macular whitening with a cherry-red spot, markedly dilated and tortuous retinal veins, and hemorrhages both around the disk and extending into the macula and the periphery. Fundus fluorescein angiography showed delayed filling of retinal vasculature, dilated and tortuous retinal veins, and blocked fluorescence around and beyond the optic disk. Optical coherence tomography scan at presentation showed hyperreflective inner retinal layers with neurosensory detachment. Optical coherence tomography angiography showed that the vessel densities of superficial and deep capillary plexus were remarkably reduced. A diagnosis of β-thalassemia trait combined with iron deficiency anemia was made after hematologic workup. The patient was treated with a course of oral iron supplements, vasodilator (compound Xueshuantong), inhalation of a mixture of 5% carbon dioxide and 95% oxygen, and a nutritional agent (compound anisoine). Six months later, her visual acuity improved to 20/60 in the left eye with complete resolution of all clinical signs. Combined central retinal vein and artery occlusion is a rare emergency leading to acute vision loss and can manifest in patients with β-thalassemia trait with iron deficiency anemia. Prompt diagnosis and early management is important to treat underlying systemic disorders and to prevent occurrence of a similar episode in fellow eye.

Panretinal handheld OCT angiography for pediatric retinal imaging

Comprehensive visualization of retina morphology is essential in the diagnosis and management of retinal diseases in pediatric populations. Conventional imaging techniques often face challenges in effectively capturing the peripheral retina, primarily due to the limitations in current optical designs, which lack the necessary field of view to characterize the far periphery. To address this gap, our study introduces a novel ultra-widefield optical coherence tomography angiography (OCTA) system. This system, specifically tailored for pediatric applications, incorporates an ultrahigh-speed 800 kHz swept-source laser. The system’s innovative design achieves a 140° field of view while maintaining excellent optical performance. Over the last 15 months, we have conducted 379 eye examinations on 96 babies using this system. It demonstrates marked efficacy in the diagnosis of retinopathy of prematurity, providing detailed and comprehensive peripheral retinal angiography. The capabilities of the ultra-widefield handheld OCTA system in enhancing the clarity and thoroughness of retina vascularization assessments have significantly improved the precision of diagnoses and the customization of treatment strategies. Our findings underscore the system’s potential to advance pediatric ophthalmology and broaden the scope of retinal imaging.

Assessment of Retinal Microvasculature and Choroidal Vascularity After Intra-arterial Chemotherapy for Retinoblastoma

PurposeTo evaluate changes in retinal microvascular density and choroidal vascularity in patients with retinoblastoma (RB) after intra-arterial chemotherapy (IAC). DesignRetrospective clinical cohort study. MethodsThis study included 12 unilateral RB eyes treated with IAC (RB tumour), 12 contralateral normal eyes (RB fellow), and 12 healthy controls. The macular retinal thickness and retinal microvascular structure, including foveal avascular zone (FAZ) area, the macular and peripapillary superficial vessel density (SVD) and deep vessel density (DVD), were measured by optical coherence tomography angiography (OCTA). The choroidal thickness (ChT) and choroidal vascularity, including total choroidal area (TCA), luminal area (LA), stromal area (SA) and Choroidal Vascularity Index (CVI), were measured by spectral-domain optical coherence tomography (SD-OCT). A comparison among the three groups was conducted, while the correlations among the parameters were analyzed. ResultsBetween the three cohorts, the foveal retinal thickness, the SVD, DVD, ChT, TCA, LA, SA and CVI were significantly lower in RB tumour compared to RB fellow and the control eyes (all P<0.01). There were no significant differences in the parameters between the contralateral and control eyes. The correlation analyses indicated a significant negative correlation between the total melphalan dose and foveal and parafoveal DVD, ChT, and LA. ConclusionsThe retinal microvascular density and choroidal vascularity were lower in unilateral RB treated with IAC, and seemed to be related to the total melphalan dose. Moreover there were no measurable changes in the contralateral eyes.

Retinal Vessel Analysis and Microvascular Abnormalities in Patients with Philadelphia-Negative Chronic Myeloproliferative Neoplasms.

Background: Philadelphia-negative chronic myeloproliferative neoplasms are a group of clonal hematopoietic disorders including polycythemia vera, essential thrombocythemia, and primary myelofi-brosis. These neoplasms are characterized by an increased risk of thrombotic complications. Several studies have highlighted that the study of vessels of the retina offers the opportunity to visualize, in vivo, the damage to microcirculation that is common in various systemic pathologies. Methods: in our study, forty patients underwent an ophthalmological examination, using non-invasive imaging tech-niques, for analyses of their retinal vascularization. The objective was to correlate the findings ob-tained from this study of the retina with different markers of thrombotic risk, to demonstrate the usefulness of studying retinal vessels as a possible new prognostic biomarker of thrombotic risk in patients affected by Philadelphia-negative chronic myeloproliferative neoplasms. Results: retinal imaging demonstrated changes in the microcirculation, with a reduced vascular density of the deep and superficial capillary plexuses with respect to a normal group, and a correlation between retinal changes and blood parameters. Conclusions: additional research will allow us to determine whether retinal changes in individuals with chronic myeloproliferative neoplasms could be predictive of the development of thrombotic events in these subjects.

Ocular blood flow in preterm neonates

Retinopathy of prematurity (ROP) is a disorder affecting low birthweight, preterm neonates. In the preterm eye, the retina is not fully developed and neovascularization may occur at the margin between the developed vascular retina and undeveloped avascular retina. Without timely treatment by laser or intravitreal anti-vascular endothelial growth factor (VEGF) therapy, this can lead to tractional retinal detachment and blindness. Visualization of the retina in regular examinations by indirect ophthalmoscopy is hence the current standard of care, but the exams are stressful and interpretation of images is subjective. The upregulation of VEGF in ROP would suggest an increase in ocular blood flow. In this report, we evaluate the potential of ultrafast plane-wave Doppler ultrasound (PWU) to detect increased flow velocities in the orbital vessels supplying the eye in a gentle exam with objective findings. We imaged both eyes of 50 low-birthweight preterm neonates using 18 MHz PWU. Flow velocity in the central retinal artery (CRA) and vein (CRV), and the short posterior ciliary arteries were determined and values at each ROP Stage compared. We found significantly increased velocities in the CRA and CRV in Stage 3 ROP eyes, where intervention would be considered. We compared multivariate models for identifying Stage 3 eyes comprised solely of clinical factors, solely of Doppler parameters, and clinical plus Doppler parameters. The respective models provided areas under their respective ROC curves of 0.760, 0.812, and 0.904. PWU Doppler represents a gentle, objective means for identifying neonates at risk for ROP that could complement ophthalmoscopy.

Retinal Hemorrhages in a Newborn with Prenatal Cocaine Exposure

A term male newborn small for gestational age and with microcephaly was born from uncomplicated vaginal delivery. Pregnancy was not followed up until 32 weeks. Maternal serologies and vaginal/rectal swabs were negative. Routine ophthalmoscopy revealed hemovitreous in the right eye and massive retinal hemorrhages (RH) in the left eye; subsequent RetCam II examination with fluorescein angiography revealed bilateral RH, involving the fovea in the left eye. Retinal vascularization was normal in both eyes, without signs of ischemic injury or pathological angiogenesis. Complete blood count, coagulation, and thrombophilic studies were normal; a toxicology screen, performed on a hair sample from both mother and infant, was positive for cocaine. With its significant vasoconstrictive effects, cocaine may induce ischemic-hypoxic damage in the developing retinal vascular system of the fetus, leading to extensive RH. Although cocaine-related RH is indistinguishable from other birth-related RH, the formers persist for longer periods, warranting prolonged follow-up and long-term evaluation of visual function.

Mechanical Ventilation, Retinal Avascularity and Rate of Vascularisation: A Triad of Predictors for Retinopathy of Prematurity Treatment.

The temporal avascular area of the retina and the duration of mechanical ventilation (DMV) may predict the need to treat retinopathy of prematurity (ROP). This study considers whether the rate of retinal vascularisation and related risk factors should be included in a predictive model of the need for ROP treatment. This single-centre, observational retrospective case-control study was conducted on 276 preterm infants included in an ROP screening programme. All had undergone at least three examinations of the fundus. The main outcome measures considered were DMV (in days of treatment), the temporal avascular area (in disc diameters, DD) and the rate of temporal retinal vascularisation (DD/week). The multivariate logistic model that best explains ROP treatment (R2 = 63.1%) has three significant risk factors: each additional day of mechanical ventilation (OR, 1.05 [95% CI, 1.02-1.09]; p = 0.001); each additional DD of temporal avascular area (OR, 2.2 [95% CI, 1.7-2.9]; p < 0.001) and a vascularisation rate <0.5 DD/week (OR, 19.0 [95% CI, 6.5-55.5]; p < 0.001). Two tables are presented for calculating the expected need for ROP treatment according to these three risk factors. A greater DMV, a broad avascular area of the temporal retina at the first binocular screening and slow retinal vascularisation strongly predict the need for ROP treatment. The predictive model we describe must be validated externally in other centres.

Retinal Structural and Vascular Changes in Patients with Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Retinal microvascular anomalies have been identified in patients with cardiovascular conditions such as arterial hypertension, diabetes mellitus, and carotid artery disease. We conducted a systematic review and meta-analysis (PROSPERO registration number CRD42024506589) to explore the potential of retinal vasculature as a biomarker for diagnosis and monitoring of patients with coronary artery disease (CAD) through optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). We systematically examined original articles in the Pubmed, Embase, and Web of Science databases from their inception up to November 2023, comparing retinal microvascular features between patients with CAD and control groups. Studies were included if they reported sample mean with standard deviation or median with range and/or interquartile range (which were computed into mean and standard deviation). Review Manager 5.4 (The Cochrane Collaboration, 2020) software was used to calculate the pooled effect size with weighted mean difference and 95% confidence intervals (CI) by random-effects inverse variance method. Eleven studies meeting the inclusion criteria were incorporated into the meta-analysis. The findings indicated a significant decrease in the retinal nerve fiber layer (WMD -3.11 [-6.06, -0.16]), subfoveal choroid (WMD -58.79 [-64.65, -52.93]), and overall retinal thickness (WMD -4.61 [-7.05, -2.17]) among patients with CAD compared to controls (p < 0.05). Furthermore, vascular macular density was notably lower in CAD patients, particularly in the superficial capillary plexus (foveal vessel density WMD -2.19 [-3.02, -1.135], p < 0.0001). Additionally, the foveal avascular zone area was statistically larger in CAD patients compared to the control group (WMD 52.73 [8.79, 96.67], p = 0.02). Heterogeneity was significant (I2 > 50%) for most features except for subfoveal choroid thickness, retina thickness, and superficial foveal vessel density. The current meta-analysis suggests that retinal vascularization could function as a noninvasive biomarker, providing additional insights beyond standard routine examinations for assessing dysfunction in coronary arteries.