Search Results (14)

Background: This study aimed to evaluate retinal arteriole parameters using adaptive optics (AO) rtx1™ (Imagine Eyes, Orsay, France) and peripapillary and macular vessel densities with optical coherence tomography angiography (OCTA) in eyes with different stages of primary open-angle glaucoma (POAG) compared to healthy eyes. It also investigated the associations between vascular parameters and glaucoma severity, as defined by structural (OCT) and functional (visual field) changes. Methods: Fifty-seven eyes from 31 POAG patients and fifty from 25 healthy volunteers were examined. Retinal arteriole morphology was assessed using the AO rtx1™-fundus camera, which measured lumen diameter, wall thickness, total diameter, wall-to-lumen ratio (WLR), and wall cross-sectional area. OCTA was used to measure vessel densities in superficial (SCP) and deep (DCP) capillary plexuses of the macula and radial peripapillary capillary plexus (RPCP) and FAZ area. Structural OCT parameters (RNFL, GCC, rim area) and visual field tests (MD, PSD) were also performed. Results: Glaucoma eyes showed significantly thicker arteriole walls (12.8 ± 1.4 vs. 12.2 ± 1.3 µm; p = 0.030), narrower lumens (85.5 ± 10.4 vs. 100.6 ± 11.1 µm; p < 0.001), smaller total diameters (111.0 ± 10.4 vs. 124.1 ± 12.4 µm; p < 0.001), and higher WLRs (0.301 ± 0.04 vs. 0.238 ± 0.002; p < 0.001) than healthy eyes. In glaucoma patients, OCTA revealed significantly reduced vessel densities in SCP (36.39 ± 3.60 vs. 38.46 ± 1.41; p < 0.001), DCP (36.39 ± 3.60 vs. 38.46 ± 1.41; p < 0.001), and RPCP plexuses (35.42 ± 4.97 vs. 39.27 ± 1.48; p < 0.001). The FAZ area was enlarged in eyes with glaucoma (0.546 ± 0.299 vs. 0.295 ± 0.125 mm²); p < 0.001). Positive correlations were found between vessel densities and OCT parameters (RNFL, r = 0.621; GCC, r = 0.536; rim area, r = 0.489), while negative correlations were observed with visual field deficits (r = −0.517). Conclusions: Vascular deterioration, assessed by AO rtx1™ and OCTA, correlates closely with structural and functional damage in glaucoma. Retinal microcirculation changes may precede structural abnormalities in the optic nerve head. Both imaging methods enable the earlier detection, staging, and monitoring of glaucoma compared to conventional tests. Full article

(1) With persistent symptoms emerging as a possible global consequence of COVID-19, the need to understand, diagnose, and treat them is paramount. This systematic review aims to explore the potential of optical coherence tomography (OCT) and/or optical coherence tomography angiography (OCTA) in effectively diagnosing long COVID. (2) The database PubMed and, to reduce selection bias, the AI research assistant Elicit, were used to find relevant publications in the period between February 2021 and March 2024. Included publications on OCT and OCTA analysis of participants with acute COVID symptoms, those after recovery, and participants with long COVID symptoms were organized in a table. Studies with participants under the age of 18, case reports, and unrelated studies, such as pure slit-lamp examinations and subgroup analyses were excluded. (3) A total of 25 studies involving 1243 participants and 960 controls were reviewed, revealing several changes in the posterior eye. Long COVID participants displayed significant thinning in retinal layers in the OCT, including the macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL). Divergent findings in recovered cohorts featured mRNFL reduction, GCL increase and decrease, and GCL-IPL decrease. Long COVID OCTA results revealed reduced vessel density (VD) in the superficial capillary plexus (SCP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). In recovered patients, SCP consistently showed a reduction, and DCP exhibited a decrease in five out of six publications. The foveal avascular zone (FAZ) was enlarged in five out of nine publications in recovered participants. (4) During various stages of COVID-19, retinal changes were observed, but a comparison between long COVID and recovered cohorts was aggravated by diverse inclusion and exclusion criteria as well as small sample sizes. Changes in long COVID were seen in most OCT examinations as thinning or partial thinning of certain retinal layers, while in OCTA a consistently reduced vessel density was revealed. The results suggest retinal alterations after COVID that are variable in OCT and more reliably visible in OCTA. Further research with larger samples is important for advancing long COVID diagnosis and management. Full article

Background: Systemic sclerosis is a complex autoimmune disease characterized by vasculopathy, fibrosis, and immune dysregulation. Ocular manifestations in these patients are increasingly recognized, suggesting potential correlations between systemic vascular abnormalities and ocular microvascular changes. Advancements in molecular immunology and imaging technology using ocular coherence tomography (OCT) have unveiled intricate pathways underlying possible disease pathogenesis. Understanding the interplay between retinal vascular abnormalities and molecular immunology parameters could provide insights into disease mechanisms and potential biomarkers. Purpose: The aim of this study was to investigate vascular abnormalities, detected with optical coherence tomography angiography (OCT-A), in systemic sclerosis patients and to find correlations between the severity of the disease detected with molecular immunology findings and OCT-A parameters. Methods: A group of 32 systemic sclerosis patients were compared with 9 healthy controls. Ganglion cell complex thickness (GCC), retina thickness of the fovea and parafovea, nerve fiber layer thickness (RNFL) and cup/disc area ratio were investigated using OCT. Vessel density (VD) of the superficial (SCP) and deep capillary plexus (DCP) of the whole macular area and ETDRS grid, size of the foveal avascular zone (FAZ) and vessel density of the radial peripapillary capillary plexus (RPCP) were evaluated using OCT-A. Modified Rodnan skin score (mRSS), capillaroscopy and disease duration were used to stage disease severity. Results: There was a statistically significant reduction in retina thickness of the fovea and parafovea, VD of the whole DCP, VD of the SCP and DCP in ETDRS grid in the patient group compared to controls (p < 0.001). The patients presented a significant enlargement of the FAZ (p 0.005). No significant correlation between OCT and OCT-A parameters and disease severity scores was found. Conclusions: OCT-A could represent a non-invasive tool to detect retinal microvascular damage in systemic sclerosis. Full article

Golden moles (Chrysochloridae) and marsupial moles (Notoryctidae) are textbook examples of convergent evolution. Both taxa are highly adapted to subterranean lifestyles and have powerful limbs for digging through the soil/sand, ears that are adapted for low-frequency hearing, vestigial eyes that are covered by skin and fur, and the absence of optic nerve connections between the eyes and the brain. The eyes of marsupial moles also lack a lens as well as retinal rods and cones. Two hypotheses have been proposed to account for the greater degeneracy of the eyes of marsupial moles than golden moles. First, marsupial moles may have had more time to adapt to their underground habitat than other moles. Second, the eyes of marsupial moles may have been rapidly and recently vestigialized to (1) reduce the injurious effects of sand getting into the eyes and (2) accommodate the enlargement of lacrimal glands that keep the nasal cavity moist and prevent the entry of sand into the nasal passages during burrowing. Here, we employ molecular evolutionary methods on DNA sequences for 38 eye genes, most of which are eye-specific, to investigate the timing of relaxed selection (=neutral evolution) for different groups of eye-specific genes that serve as proxies for distinct functional components of the eye (rod phototransduction, cone phototransduction, lens/cornea). Our taxon sampling included 12 afrothere species, of which two are golden moles (Amblysomus hottentotus, Chrysochloris asiatica), and 28 marsupial species including two individuals of the southern marsupial mole (Notoryctes typhlops). Most of the sequences were mined from databases, but we also provide new genome data for A. hottentotus and one of the two N. typhlops individuals. Even though the eyes of golden moles are less degenerate than the eyes of marsupial moles, there are more inactivating mutations (e.g., frameshift indels, premature stop codons) in their cone phototransduction and lens/cornea genes than in orthologous genes of the marsupial mole. We estimate that cone phototransduction recovery genes were inactivated first in each group, followed by lens/cornea genes and then cone phototransduction activation genes. All three groups of genes were inactivated earlier in golden moles than in marsupial moles. For the latter, we estimate that lens/cornea genes were inactivated ~17.8 million years ago (MYA) when stem notoryctids were burrowing in the soft soils of Australian rainforests. Selection on phototransduction activation genes was relaxed much later (5.38 MYA), during the early stages of Australia’s aridification that produced coastal sand plains and eventually sand dunes. Unlike cone phototransduction activation genes, rod phototransduction activation genes are intact in both golden moles and one of the two individuals of N. typhlops. A second marsupial mole individual has just a single inactivating mutation in one of the rod phototransduction activation genes (PDE6B). One explanation for this result is that some rod phototransduction activation genes are pleiotropic and are expressed in extraocular tissues, possibly in conjunction with sperm thermotaxis. Full article

Purpose: To describe anatomical peculiarities associated with axial elongation in the human myopic eye. Methods: Reviewing the results of previous histomorphometrical investigations of enucleated human globes, as well as reviewing findings obtained in population-based studies and hospital-based clinical investigations of myopic patients and non-myopic individuals. Results: Myopic axial elongation is associated with a change from a mostly spherical eye shape to a prolate ellipsoid form. It is combined with choroidal and scleral thinning, most pronounced at the posterior pole and less pronounced in the fundus midperiphery. In the fundus midperiphery, the retina and density of the retinal pigment epithelium (RPE) and photoreceptors decrease with a longer axial length, while in the macular region, retinal thickness, RPE cell density, and choriocapillaris thickness are not related to axial length. With axial elongation, a parapapillary gamma zone develops, leading to an enlargement of the optic disc-fovea distance and a decrease in angle kappa. Axial elongation is also correlated with an increase in the surface and volume of Bruch’s membrane (BM), while BM thickness remains unchanged. Axial elongation causes moderately myopic eyes to show a shift of BM opening to the foveal direction so that the horizontal disc diameter becomes shorter (with a consequent vertical ovalization of the optic disc shape), a temporal gamma zone develops, and the optic nerve exit takes an oblique course. Features of high myopia are an enlargement of the RPE opening (myopic parapapillary beta zone) and BM opening (secondary macrodisc), elongation and thinning of the lamina cribrosa, peripapillary scleral flange (parapapillary delta zone) and peripapillary choroidal border tissue, secondary BM defects in the macular region, myopic maculoschisis, macular neovascularization, and cobblestones in the fundus periphery. Conclusions: These features combined may be explained by a growth in BM in the fundus midperiphery leading to axial elongation. Full article

Graves’ disease is an autoimmune disorder in which hyperthyroidism results in various systematic symptoms, with about 30% of patients presenting with Graves’ eye disease (GED). The majority of patients with GED develop mild symptoms, including eyelid retraction, exposure of the globe, superior rectus–levator muscle complex inflammation, and fat expansion, leading to exophthalmos. More severe cases can result in extraocular muscle enlargement, restricted ocular movement, eyelid and conjunctival edema, and compression of the optic nerve leading to compressive optic neuropathy (CON). GED severity can be classified using the Clinical Activity Score, European Group on Graves’ Orbitopathy scale, NO SPECS Classification system, and VISA system. CT and MRI aid in the diagnosis of GED through the demonstration of orbital pathology. Several recent studies have shown that MRI findings correlate with disease severity and can be used to evaluate CON. Mild cases of GED can be self-limiting, and patients often recover spontaneously within 2–5 years. When medical treatment is required, immunomodulators or radiotherapy can be used to limit immunologic damage. Surgery may be needed to improve patient comfort, preserve the orbit, and prevent vision loss from optic nerve compression or breakdown of the cornea. Full article

Purpose: To study the foveal avascular zone (FAZ) and the vessel densities (VD) in diabetic patients using optical coherence tomography angiography (OCT-A) and inner retinal layer changes to compare patients affected by type 1 diabetes (DM1) and type 2 diabetes (DM2). Methods: Cross-sectional observational study involving 150 eyes of 150 patients with DM1, and 155 eyes of 155 patients with DM2 with diabetic retinopathy (DR). Retinal nerve fiber layer (RNFL) and Ganglion cell layer (GCL) were evaluated. OCT-A studied both FAZ and VD at the level of the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Results: A statistically significant difference in FAZ area and foveal VD measured at the SCP (p < 0.001) was noted between DM1 and DM2 groups when comparing patients with mild and moderate non-proliferative diabetic retinopathy (NPDR), while no differences were found in the severe NPDR and proliferative diabetic retinopathy (PDR) subgroups. Duration of diabetes and stage of DR were directly correlated with enlargement of FAZ area and inversely correlated with foveal VD measured at SCP. RNFL and GCL were not different between DM1 and DM2 groups. Conclusion: Changes in OCT-A parameters detected in FAZ area and VD of diabetic patients with different stages of DR may help to predict the risk for progression of the disease. Full article

Myocilin is an enigmatic glaucoma-associated glycoprotein whose biological role remains incompletely understood. To gain novel insight into its normal function, we used transposon-mediated transgenesis to generate the first zebrafish line stably overexpressing myocilin [Tg(actb1:myoc-2A-mCherry)]. qPCR showed an approximately four-fold increased myocilin expression in transgenic zebrafish embryos (144 hpf). Adult (13 months old) transgenic animals displayed variable and age-dependent ocular anterior segment alterations. Almost 60% of two-year-old male, but not female, transgenic zebrafish developed enlarged eyes with severe asymmetrical and variable abnormalities in the anterior segment, characterized by corneal limbus hypertrophy, and thickening of the cornea, iris, annular ligament and lens capsule. The most severe phenotype presented small or absent ocular anterior chamber and pupils, due to iris overgrowth along with dysplastic retinal growth and optic nerve hypertrophy. Immunohistochemistry revealed increased presence of myocilin in most altered ocular tissues of adult transgenic animals, as well as signs of retinal gliosis and expanded ganglion cells and nerve fibers. The preliminary results indicate that these cells contributed to retinal dysplasia. Visual impairment was demonstrated in all old male transgenic zebrafish. Transcriptomic analysis of the abnormal transgenic eyes identified disrupted expression of genes involved in lens, muscular and extracellular matrix activities, among other processes. In summary, the developed transgenic zebrafish provides a new tool to investigate this puzzling protein and provides evidence for the role of zebrafish myocilin in ocular anterior segment and retinal biology, through the influence of extracellular matrix organization and cellular proliferation. Full article

Multiple sclerosis (MS) is an inflammatory and neurodegenerative, potentially disabling disease of the central nervous system. OCT (Optical Coherence Tomography) and OCT-A (Optical Coherence Tomography with Angiography) are imaging techniques for the retina and choroid that are used in the diagnosis and monitoring of ophthalmological conditions. Their use has recently expanded the study of several autoimmune disorders, including MS. Although their application in MS remains unclear, the results seem promising. This review aimed to provide insight into the most recent OCT and OCT-A findings in MS and may function as a reference point for future research. According to the current literature, the retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform complex (GC-IPL) are significantly reduced in people with MS and are inversely correlated with disease duration. The use of OCT might help distinguish between MS and neuromyelitis optica spectrum disorders (NMOSD), as the latter presents with more pronounced thinning in both the RNFL and GC-IPL. The OCT-A findings in MS include reduced vessel density in the macula, peripapillary area, or both, and the enlargement of the foveal avascular zone (FAZ) in the setting of optic neuritis. Additionally, OCT-A might be able to detect damage in the very early stages of the disease as well as disease progression in severe cases. Full article

Intracranial aneurysms (IAs) are localized enlargements of cerebral blood vessels that cause substantial rates of mortality and morbidity in humans. The rupture possibility of these aneurysms is a critical medical challenge for physicians during treatment planning. This treatment planning while assessing the rupture potential of aneurysms becomes more complicated when they are constrained by an adjacent structure such as optic nerve tissues or bones, which is not widely studied yet. In this work, we considered and studied a constitutive model to investigate the bio-mechanical response of image-based patient-specific IA data using cardiovascular structural mechanics equations. We performed biomechanical modeling and simulations of four different patient-specific aneurysms’ data (three middle cerebral arteries and one internal carotid artery) to assess the rupture potential of those aneurysms under a plane contact constraint. Our results suggest that aneurysms with plane contact constraints produce less or almost similar maximum wall effective stress compared to aneurysms with no contact constraints. In our research findings, we observed that a plane contact constraint on top of an internal carotid artery might work as a protective wall due to the 16.6% reduction in maximum wall effective stress than that for the case where there is no contact on top of the aneurysm. Full article

Eye-drop recombinant human nerve growth factor (ed-rhNGF) has proved to recover the retina and optic nerve damage in animal models, including the unilateral optic nerve crush (ONC), and to improve visual acuity in humans. These data, associated with evidence that ed-rhNGF stimulates the brain derived neurotrophic factor (BDNF) in retina and cortex, suggests that NGF might exert retino-fugal effects by affecting BDNF and its receptor TrkB. To address these questions, their expression and relationship with the GABAergic and glutamatergic transmission markers, GAD65 and GAD67, vesicular inhibitory amino acid transporter (VGAT), and vesicular glutamate transporters 1 and 2 (VGLUT-1 and VGLUT-2) were investigated in adult ONC rats contralateral and ipsilateral visual cortex (VCx). Ed-rhNGF recovers the ONC-induced alteration of GABAergic and glutamatergic markers in contralateral VCx, induces an upregulation of TrkB, which is positively correlated with BDNF precursor (proBDNF) decrease in both VCx sides, and strongly enhances TrkB+ cell soma and neuronal endings surrounded by GAD65 immuno-reactive afferents. These findings contribute to enlarging the knowledge on the mechanism of actions and cellular targets of exogenously administrated NGF, and suggest that ed-rhNGF might act by potentiating the activity-dependent TrkB expression in GAD+ cells in VCx following retina damage and/or ONC. Full article

The purpose of this study is to identify salient magnetic resonance imaging (MRI) findings of pediatric IIH, to determine the relevance of these findings with regard to disease pathogenesis, and to relate these findings to the clinical presentation towards identification of risk factors of disease. A retrospective, a case–control study of 38 pediatric patients with and 24 pediatric patients without IIH from the ophthalmology department at a tertiary care center was performed. Clinical data, including ophthalmic findings and lumbar puncture results, were recorded. Neuroimaging, including both MRI and magnetic resonance venography (MRV), was evaluated for perioptic subarachnoid space diameter enlargement, posterior globe flattening, optic nerve head protrusion, empty or partially empty sella turcica, dural venous sinus abnormalities, skull base crowding, and prominent arachnoid granulations. Compared with controls, IIH patients had larger perioptic subarachnoid space diameters, higher incidences of posterior globe flattening, protrusion of the optic nerve heads, an empty sella turcica, and dural venous sinus abnormalities. A perioptic subarachnoid space diameter of ≥5.2 mm was identified as an independent predictor of IIH (p < 0.001) with sensitivity of 87% and specificity of 67%. Several significant MRI findings in pediatric IIH were identified. Using a model that uniquely incorporated clinical and MRI findings at presentation, we provide a framework for risk stratification for the diagnosis of pediatric IIH which may be utilized to facilitate diagnosis. Future prospective work is needed to further validate the model developed in this study. Full article

Inherited neurodegeneration of the optic nerve is a paradigm in neurology, as many forms of isolated or syndromic optic atrophy are encountered in clinical practice. The retinal ganglion cells originate the axons that form the optic nerve. They are particularly vulnerable to mitochondrial dysfunction, as they present a peculiar cellular architecture, with axons that are not myelinated for a long intra-retinal segment, thus, very energy dependent. The genetic landscape of causative mutations and genes greatly enlarged in the last decade, pointing to common pathways. These mostly imply mitochondrial dysfunction, which leads to a similar outcome in terms of neurodegeneration. We here critically review these pathways, which include (1) complex I-related oxidative phosphorylation (OXPHOS) dysfunction, (2) mitochondrial dynamics, and (3) endoplasmic reticulum-mitochondrial inter-organellar crosstalk. These major pathogenic mechanisms are in turn interconnected and represent the target for therapeutic strategies. Thus, their deep understanding is the basis to set and test new effective therapies, an urgent unmet need for these patients. New tools are now available to capture all interlinked mechanistic intricacies for the pathogenesis of optic nerve neurodegeneration, casting hope for innovative therapies to be rapidly transferred into the clinic and effectively cure inherited optic neuropathies. Full article

Krabbe disease (KD) is an autosomal recessive lysosomal storage disorder caused by dysfunctional galactosylceramidase activity. Infantile form is the most common subtype, occurring at about 6-month of age. We present a rare case of infantile KD with magnetic resonance imaging showing white matter, thalamic and basal ganglia lesions rarely associated with an enlargement of the optic nerves bilaterally. Full article