Abstract: Acute retinal arterial ischemia, which includes transient monocular vision loss (TMVL), branch retinal artery occlusion (BRAO), central retinal artery occlusion (CRAO) and ophthalmic artery occlusion (OAO), is most commonly the consequence of an embolic phenomenon from the ipsilateral carotid artery, heart or aortic arch, leading to partial or complete occlusion of the central retinal artery (CRA) or its branches. Acute retinal arterial ischemia is the ocular equivalent of acute cerebral ischemia and is an ophthalmic and medical emergency. Patients with acute retinal arterial ischemia are at a high risk of having further vascular events, such as subsequent strokes and myocardial infarctions (MIs). Therefore, prompt diagnosis and urgent referral to appropriate specialists and centers is necessary for further work-up (such as brain magnetic resonance imaging with diffusion weighted imaging, vascular imaging, and cardiac monitoring and imaging) and potential treatment of an urgent etiology (e.g., carotid dissection or critical carotid artery stenosis). Since there are no proven, effective treatments to improve visual outcome following permanent retinal arterial ischemia (central or branch retinal artery occlusion), treatment must focus on secondary prevention measures to decrease the likelihood of subsequent ischemic events.
Abstract: Optical coherence tomography (OCT) is an ocular imaging technique that can complement the neuro-ophthalmic assessment, and inform our understanding regarding functional consequences of neuroaxonal injury in the afferent visual pathway. Indeed, OCT has emerged as a surrogate end-point in the diagnosis and follow up of several demyelinating syndromes of the central nervous system (CNS), including optic neuritis (ON) associated with: multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. Recent advancements in enhanced depth imaging (EDI) OCT have distinguished this technique as a new gold standard in the diagnosis of optic disc drusen (ODD). Moreover, OCT may enhance our ability to distinguish cases of papilledema from pseudopapilledema caused by ODD. In the setting of idiopathic intracranial hypertension (IIH), OCT has shown benefit in tracking responses to treatment, with respect to reduced retinal nerve fiber layer (RNFL) measures and morphological changes in the angling of Bruch’s membrane. Longitudinal follow up of OCT measured ganglion cell-inner plexiform layer thickness may be of particular value in managing IIH patients who have secondary optic atrophy. Causes of compressive optic neuropathies may be readily diagnosed with OCT, even in the absence of overt visual field defects. Furthermore, OCT values may offer some prognostic value in predicting post-operative outcomes in these patients. Finally, OCT can be indispensable in differentiating optic neuropathies from retinal diseases in patients presenting with vision loss, and an unrevealing fundus examination. In this review, our over-arching goal is to highlight the potential role of OCT, as an ancillary investigation, in the diagnosis and management of various optic nerve disorders.
Abstract: Myasthenia gravis (MG) is an autoimmune antibody-mediated disorder which causes fluctuating weakness in ocular, bulbar and limb skeletal muscles. There are two major clinical types of MG. Ocular MG (OMG) affects extra ocular muscles associated with eye movement and eyelid function and generalized MG results in muscle weakness throughout the body. Patients with OMG have painless fluctuating extra ocular muscles weakness, diplopia and ptosis accompanied by normal visual acuity and pupillary function. Frequently, patients with OMG develop generalized MG over 24 months. Pure OMG is more often earlier in onset (<45 years) than generalized MG. It can also occur as part of an immune-genetic disorder or paraneoplastic syndrome related to thymus tumors. Diagnosis is based on clinical manifestations, laboratory findings, electrophysiological evaluation and pharmacologic tests. Therapeutic strategies for MG consist of symptom relieving medications (e.g., acetylcholine esterase inhibitors), immunosuppressive agents, and surgical intervention (e.g., thymectomy).
Abstract: The article discusses the early abandonment of mechanical theories about eye enlargement in degenerative myopia at the turn of the 20th century. At that time, the number of theories about myopia grew unrestricted, but with scant support from the experimental field. The mechanical theories vanished as a new wave of metabolism-based theories appeared, propelled by the huge advances in molecular biology. Modern techniques allow reconsidering those theories and to put them to test with higher confidence.
Background: Pericytes are contractile cells that wrap along the walls of capillaries. In the brain, pericytes play a crucial role in the regulation of capillary diameter and vascular blood flow in response to metabolic demand. During ischemia, it has been suggested that pericytes may constrict capillaries, and that pericytes remain constricted after reperfusion thus resulting in impaired blood flow.
Methods: Here, we used a mouse model of retinal ischemia based on ligation of the central retinal artery to characterize the role of pericytes on capillary constriction. Ischemia was induced in transgenic mice carrying the NG2 promoter driving red fluorescent protein expression to selectively visualize pericytes (line NG2:DsRed).Changes in retinal capillary diameter at 1 hr after ischemia were measured ex vivo in whole-mounted retinas from ischemic and control eyes (n=4–6/group) using a stereological approach. Vessels and pericytes were three-dimensionally reconstructed using IMARIS (Bitplane). Furthermore, we used a novel and minimally invasive two-photon microscopy approach that allowed live imaging of microvasculature changes in the retina.
Results: Our data show a generalized reduction in capillary diameter in ischemic retinas relative to sham-operated controls in all vascular plexus (ischemia: 4.7±0.2 μm, control: 5.2±0.2 μm, student’s t-test, P<0.001). Analysis of the number of capillary constrictions at pericyte locations, visualized in NG2:DsRed mice, demonstrated a substantial increase in ischemic retinas relative to the physiological capillary diameter reductions observed in controls (ischemia: 1,038±277 constrictions at pericyte locations, control: 60±36 constrictions at pericyte locations, student’s t-test, P<0.01). Live imaging using two-photon microscopy confirmed robust capillary constriction at the level of pericytes on retinal capillaries during ischemia (n=6–8/group).
Conclusions: Collectively, our data demonstrate that ischemia promotes rapid pericyte constriction on retinal capillaries causing major microvascular dysfunction in this tissue. To identify the molecular mechanisms underlying the pathological response of pericytes during ischemia, we are currently carrying out experiments in mice and zebrafish to modulate signaling pathways involved in calcium dynamics leading to contractility in these cells.
Background: Decrease of ocular blood flow has been linked to the pathogenesis of ocular diseases such as glaucoma and age-related macular degeneration. Current methods that measure the pulsatile blood flow have major limitations, including the assumption that ocular rigidity is the same in all eyes. Our group has recently developed a new method to measure the pulsatile choroidal volume change by direct visualization of the choroid with OCT imaging and automated segmentation. Our goal in this study is to describe the distribution of PCBF in a healthy Caucasian population.
Methods: Fifty-one subjects were recruited from the Maisonneuve-Rosemont Hospital Ophthalmology Clinic and underwent PCBF measurement in one eye. The distribution of PCBF in healthy eyes was assessed.
Results: The distribution of PCBF among the healthy eyes was found to be 3.94±1.70 μL with this technique.
Conclusions: This study demonstrates the normal range of PCBF values obtained in a healthy Caucasian population. This technique could be used for further investigation of choroid pulsatility and to study glaucoma pathophysiology.
Background: Retinal endothelial cells are very active and contribute to the integrity of the neurovascular unit. Vascular dysfunction has been proposed to contribute to the pathogenesis of glaucoma. Here, we evaluated the hypothesis that ocular hypertension triggers mitochondrial alterations in endothelial cells impairing the integrity of the blood retinal barrier (BRB).
Methods: Ocular hypertension was induced by injection of magnetic microbeads into the anterior chamber of EndoMito-EGFP mice, a strain expressing green fluorescent protein selectively in the mitochondria of endothelial cells. Capillary density, mitochondrial volume, and the number of mitochondrial components were quantified in 3D-reconstructed images from whole-mounted retinas using Imaris software. Dynamin-related protein (DRP-1), mitofusin-2 (MFN-2) and optic atrophy-1 (OPA-1) expression were assessed by western blot analysis of enriched endothelial cells. Mitochondrial structure was evaluated by transmission electron microscopy (TEM) and oxygen consumption rate was monitored by Seahorse analysis. The integrity of the BRB was evaluated by quantifying Evans blue leakage.
Results: Our data demonstrate that two and three weeks after ocular hypertension induction, the total mitochondria volume in endothelial cells decreased from 0.140±0.002 μm3 from non-injured retinas to 0.108±0.005 and 0.093±0.007 μm3, respectively in glaucomatous eyes (mean ± S.E.M, ANOVA, P<0.001; N=6/group). Frequency distribution showed a substantial increase of smaller mitochondria complexes (<0.5 μm3) in endothelial cells from glaucomatous retinas. Significant upregulation of DRP-1 was found in vessels isolated from glaucomatous retinas compared to the intact retinas, while MFN-2 and OPA-1 expression was not affected. Structural alteration in endothelial cell mitochondria was confirmed by TEM, which were accompanied by a 1.93-fold reduction in the oxygen consumption rate as well as 2.6-fold increase in vasculature leakage in glaucomatous retinas (n=3–6/group). In addition, this model did not trigger changes in the density of the vascular network, suggesting that mitochondrial fragmentation was not due to endothelial cell loss.
Conclusions: This study shows that ocular hypertension leads to early alterations in the dynamic of endothelial cell mitochondria, contributing to vascular dysfunction in glaucoma.
