Relative Afferent Pupillary Defects in Homonymous Visual Field Defects Caused by Stroke of the Occipital Lobe Using Pupillometer

Takizawa, Go; Miki, Atsushi; Maeda, Fumiatsu; Goto, Katsutoshi; Araki, Syunsuke; Yamashita, Tsutomu; Ieki, Yoshiaki; Kiryu, Junichi; Yaoeda, Kiyoshi

doi:10.1080/01658107.2017.1367012

Cited by 7 publications

(8 citation statements)

References 28 publications

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“…In primates, the number of ipsilateral and contralateral RGC axons is approximately equal . In humans, the ratio of crossed to uncrossed fibers in the chiasma is 53:47 . In mice, only 3 to 5% of all RGC axons are ipsilateral .…”

Section: Results and Discussionmentioning

confidence: 99%

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Protein Drug Delivery Using a Novel Maxillofacial Technique Targeting the Visual Pathway in the Brain, the Optic Nerve, and the Retina

Rajendran,

Arunachalam,

Chidambaram

et al. 2023

ACS Chem. Neurosci.

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Protein drugs are used for treating many diseases of the eye and the brain. The formidable blood neural barriers prevent the delivery of these drugs into the eye and the brain. Hence, there is a need for a protein drug delivery system to deliver large proteins across blood-neural barriers. Low half-life, poor penetration of epithelial barriers, low stability, and immunogenicity limit the use of non-invasive systemic routes for delivering proteins. In this pre-clinical study, the efficacy of a new maxillofacial route for administering protein drugs using a novel drug delivery system is compared with systemic administration through intra-peritoneal injection and ocular administration through topical eye drops and subconjunctival and intravitreal injections. Bevacizumab and retinoschisin proteins were administered using the maxillofacial technique along with systemic and ocular routes in wild-type male C57BL/6J mice. Liquid chromatography with tandem mass spectrometry and western blot was used to detect bevacizumab in tissue samples. Furthermore, immunohistochemistry was performed to detect the presence and localization of bevacizumab and retinoschisin in the retina and brain. The maxillofacial route of delivery could target the brain including regions involved in the visual pathway and optic nerve. The maxillofacial technique and intravitreal injection were effective in delivering the drugs into the retina. A new concept based on the glymphatic pathway, cerebrospinal fluid drug distribution, and the crossover of ipsilateral optic nerve fibers at optic chiasma is proposed to explain the presence of the drug in contralateral eye following maxillofacial administration and intravitreal injection.

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Section: Results and Discussionmentioning

confidence: 99%

“…32 In humans, the ratio of crossed to uncrossed fibers in the chiasma is 53:47. 33 In mice, only 3 to 5% of all RGC axons are ipsilateral. 32 In rodents, uncrossed axons also approach the chiasmal midline.…”

Section: Resultsmentioning

confidence: 99%

Protein Drug Delivery Using a Novel Maxillofacial Technique Targeting the Visual Pathway in the Brain, the Optic Nerve, and the Retina

Rajendran,

Arunachalam,

Chidambaram

et al. 2023

ACS Chem. Neurosci.

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show abstract

“…In primates, the number of ipsilateral and contralateral RGC axons is approximately equal 37 . In humans, ratio of crossed to uncrossed fibers in the chiasm of 53:47 38 . In mouse, only 3% to 5% of all RGC axons are ipsilateral 37 .…”

Section: Discussionmentioning

confidence: 99%

A novel maxillofacial technique to deliver drugs to the visual pathway, the optic nerve and the retina using the glymphatic system

Rajendran

Chidambaram

Srikanth

et al. 2022

Preprint

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The blood neural barriers are formidable barriers that prevent delivery of drugs into the eye and the brain. Currently, large biologics are used for treating many diseases of the eye and the brain. But the blood retinal barrier and the blood brain barrier prevent entry of these useful drugs into the eye and the brain respectively. Hence, there is a need for a drug delivery technique to bypass these natural barriers. Bevacizumab (Avastin) is a full length humanized monoclonal antibody with a molecular weight of 149kda. It binds to circulating vascular endothelial growth factor A and prevents interaction with vascular endothelial growth receptors. This results in blocking endothelial response and tumor vascularization. Bevacizumab is used to prevent choroidal neovascularization in age related macular degeneration and to prevent retinal neovascularization in diabetic retinopathy. It is also used for treating certain types of brain cancer. But it crosses neither the blood retinal barrier nor the blood brain barrier. This in vivo mouse study assessed the delivery of a commercial formulation of bevacizumab into the retina of mice using different ocular techniques like topical drops, subconjunctival injection, intravitreal injection and a novel maxillofacial technique. The objective was to assess whether the novel maxillofacial drug delivery technique could deliver drugs into the retina and to compare the efficacy of the maxillofacial technique with the mentioned ocular techniques. The distribution of bevacizumab was further compared with retinoschisin which is a small protein with a molecular weight of 24kda. Intravitreal injection and maxillofacial technique were effective in delivering drugs into the retina. In addition, the maxillofacial technique could target the brain including regions involved in the visual pathway and the optic nerve. The glymphatic pathway could also be targeted for drug delivery. Drug was also detected in the contralateral optic nerve and retina. Based on our study findings, we propose a new concept to explain the presence of the drug in the contralateral eye. We propose that after maxillofacial drug delivery, early distribution of the drug can occur in the CSF at the optic chiasma from the brain via the glymphatic system. In the case of the intravitreal injection, the drug from the experimental eye may be cleared through the glymphatic pathway of the ipsilateral optic nerve into the CSF surrounding the nerve. The crossover of the ipsilateral optic nerve fibers at the optic chiasma can result in further distribution of the drug in the CSF at the optic chiasma. From the region of the optic chiasma, the drug can distribute into the CSF surrounding the contralateral optic nerve. The drug can be then distributed into the contralateral optic nerve through the glymphatic pathway and be delivered into the contralateral eye. The drug can be further cleared into the aqueous of the contralateral eye through the anterior clearance pathway.

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“…Meanwhile, certain other studies further explored the possibility of such pupillometer systems (commercially available or lab-based prototypes) to detect and quantify Relative Afferent Pupillary Defects (RAPDs) that showed promising results with a high positive correlation with conventional methods i.e. SFT and Neutral Density Filter 19 , 20 , 33 , 34 .…”

Section: Discussionmentioning

confidence: 99%

A haploscope based binocular pupillometer system to quantify the dynamics of direct and consensual Pupillary Light Reflex

Meethal

Mazumdar

Morshchavka

et al. 2021

Sci Rep

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This study described the development of a haploscope-based pupillometer for the parametrization of the Pupillary Light Reflex (PLR), and its feasibility in a set of 30 healthy subjects (light or dark-colored irides) and five patients diagnosed with Relative Afferent Pupillary Defect (RAPD). Our supplementary aim focused on evaluating the influence of iris colour on the PLR to decide whether a difference in PLR parameters should be anticipated when this system is used across ethnicities. All the participants underwent a customized pupillometry protocol and the generated pupil traces, captured by an eye tracker, were analyzed using exponential fits to derive PLR parameters. A Pupil Response Symmetry (PRS) coefficient was calculated to predict the presence of RAPD. The mean (SD) Initial PD during dilation (3.2 (0.5) mm) and the minimum PD during constriction (2.9 (0.4) mm) in the light iris group had a statistically significant (p < 0.001) higher magnitude compared to the dark iris group. The normal limits of the PRS coefficient ranged from − 0.20 to + 1.07 and all RAPD patients were outside the calculated normal limits. This proposed system, analysis strategies, and the tested metrics showed good short-term repeatability and the potential in detecting pupil abnormalities in neuro-ophthalmic diseases.

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Relative Afferent Pupillary Defects in Homonymous Visual Field Defects Caused by Stroke of the Occipital Lobe Using Pupillometer

Cited by 7 publications

References 28 publications

Protein Drug Delivery Using a Novel Maxillofacial Technique Targeting the Visual Pathway in the Brain, the Optic Nerve, and the Retina

Protein Drug Delivery Using a Novel Maxillofacial Technique Targeting the Visual Pathway in the Brain, the Optic Nerve, and the Retina

A novel maxillofacial technique to deliver drugs to the visual pathway, the optic nerve and the retina using the glymphatic system

A haploscope based binocular pupillometer system to quantify the dynamics of direct and consensual Pupillary Light Reflex

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