The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Alfredo A Sadun - One of the best experts on this subject based on the ideXlab platform.
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correction Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep wake activity in pre symptomatic alzheimer s disease
PLOS ONE, 2019Co-Authors: Angela J Oh, Giulia Amore, William Sultan, Samuel Asanad, Jason C Park, Martina Romagnoli, Chiara La Morgia, Rustum Karanjia, Michael G Harrington, Alfredo A SadunAbstract:BACKGROUND: Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body's circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer's disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic Pupillometry may be a potential biomarker for early diagnosis and progression of AD. METHODS: We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic Pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. RESULTS: Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic Pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. CONCLUSIONS: The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.
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Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep wake activity in pre symptomatic alzheimer s disease
PLOS ONE, 2019Co-Authors: Giulia Amore, William Sultan, Samuel Asanad, Jason C Park, Martina Romagnoli, Chiara La Morgia, Rustum Karanjia, Michael G Harrington, Alfredo A SadunAbstract:Background Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body’s circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer’s disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic Pupillometry may be a potential biomarker for early diagnosis and progression of AD. Methods We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic Pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. Results Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic Pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. Conclusions The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.
Jason C Park - One of the best experts on this subject based on the ideXlab platform.
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correction Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep wake activity in pre symptomatic alzheimer s disease
PLOS ONE, 2019Co-Authors: Angela J Oh, Giulia Amore, William Sultan, Samuel Asanad, Jason C Park, Martina Romagnoli, Chiara La Morgia, Rustum Karanjia, Michael G Harrington, Alfredo A SadunAbstract:BACKGROUND: Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body's circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer's disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic Pupillometry may be a potential biomarker for early diagnosis and progression of AD. METHODS: We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic Pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. RESULTS: Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic Pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. CONCLUSIONS: The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.
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Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep wake activity in pre symptomatic alzheimer s disease
PLOS ONE, 2019Co-Authors: Giulia Amore, William Sultan, Samuel Asanad, Jason C Park, Martina Romagnoli, Chiara La Morgia, Rustum Karanjia, Michael G Harrington, Alfredo A SadunAbstract:Background Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body’s circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer’s disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic Pupillometry may be a potential biomarker for early diagnosis and progression of AD. Methods We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic Pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. Results Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic Pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. Conclusions The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.
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the pupillary light reflex in idiopathic intracranial hypertension
Investigative Ophthalmology & Visual Science, 2016Co-Authors: Jason C Park, Heather E Moss, Jason J McananyAbstract:Idiopathic intracranial hypertension (IIH) is a condition of elevated intracranial pressure (ICP) for which a cause cannot be determined. Loss of visual function is the primary morbidity for most IIH patients, with approximately 10% of patients progressing to bilateral blindness.1,2 As reviewed elsewhere,3 visual dysfunction in IIH appears to be due to a series of events initiated by increased ICP. Elevation in ICP likely produces increased pressure around the distal optic nerve, which, in turn, results in axoplasmic flow stasis.4–6 Reduced axoplasmic transport produces intra-axonal edema,7 which is likely followed by venule compression, ischemia, and loss of visual function. Because visual function within the central visual field is typically normal, or nearly normal, until the late stages of the disease8,9 vision loss in IIH is most commonly characterized by standard automated perimetry to measure peripheral visual field sensitivity.1,8–10 However, not all IIH patients have marked visual field abnormalities, and ganglion cell dysfunction may precede measurable reductions assessed by perimetry.11 Moreover, perimetry is an inherently subjective test and it is vulnerable to patient error. Objective assessments of visual pathway function in IIH may provide new insight into vision loss associated with the disease and could have the potential to provide additional data upon which clinical management decisions can be based. Objective measures of RGC function have been performed in patients with IIH using electrophysiological techniques. For example, previous work has shown that the amplitude of the pattern electroretinogram (pERG) can be reduced in patients with IIH.12 However, standard pERG measurements are limited in that they primarily assess function within the central visual field. More recently, it was shown that the photopic negative response (PhNR), a late negative component of the full-field photopic single-flash ERG that originates largely from RGCs,13,14 can also be abnormal in patients with IIH.11 Pupillometry is an additional objective technique that can assess inner retina, outer retina, and subcortical function, which may have application to patients with IIH. The response of the pupil to a flash of light (the pupillary light reflex; PLR) is a complex response with contributions from more than one photoreceptor type. However, by altering the adaptation conditions and stimulus characteristics, contributions of the rod pathway, cone pathway, and intrinsically photosensitive RGC (ipRGC) pathway, which contains the photopigment melanopsin,15,16 can be assessed.17–19 Thus, the PLR is a powerful tool because it provides insight into ipRGC function, as well as rod and cone inputs into the ipRGCs. The PLR has been useful for understanding diseases of the inner retina and optic nerve, such as in hereditary optic neuropathies,20–22 glaucoma,23–26 and ischemic optic neuropathy.27 To date, the PLR has not been reported in patients with IIH. Pupillometry is a promising approach for functional assessment in IIH because it shares many of the advantages of PhNR measurement, in that it is noninvasive, objective, performed quickly with minimal patient demands, does not require refraction or steady fixation, and can be measured using full-field stimuli. Additionally, Pupillometry does not require pupil dilation and can provide measures of rod, cone, and melanopsin RGC function. The generators of the PLR likely differ from those of the PhNR, as Pupillometry selectively targets ipRGCs. Although IIH is not typically associated with outer retina abnormalities, a recent report has shown cone receptor density loss in a patient with IIH28 and an earlier report showed light adapted flicker ERG deficits in patients with chronic papilledema.29 Thus, Pupillometry may provide new insight into outer retina function in patients with IIH. The goal of the present study was to evaluate rod-, cone-, and melanopsin-mediated PLRs in patients with IIH. These pupil responses were assessed using a previously published paradigm,19 with slight modification, in patients with IIH and in visually-normal control subjects. The patients' PLRs were compared with other measures of visual function including Humphrey visual field mean deviation (HVF MD) scores and PhNR amplitude. The results of the present study are intended to determine the extent to which Pupillometry can be used as a clinical tool to assess retinal dysfunction in patients with IIH.
Rustum Karanjia - One of the best experts on this subject based on the ideXlab platform.
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correction Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep wake activity in pre symptomatic alzheimer s disease
PLOS ONE, 2019Co-Authors: Angela J Oh, Giulia Amore, William Sultan, Samuel Asanad, Jason C Park, Martina Romagnoli, Chiara La Morgia, Rustum Karanjia, Michael G Harrington, Alfredo A SadunAbstract:BACKGROUND: Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body's circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer's disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic Pupillometry may be a potential biomarker for early diagnosis and progression of AD. METHODS: We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic Pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. RESULTS: Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic Pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. CONCLUSIONS: The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.
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Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep wake activity in pre symptomatic alzheimer s disease
PLOS ONE, 2019Co-Authors: Giulia Amore, William Sultan, Samuel Asanad, Jason C Park, Martina Romagnoli, Chiara La Morgia, Rustum Karanjia, Michael G Harrington, Alfredo A SadunAbstract:Background Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body’s circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer’s disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic Pupillometry may be a potential biomarker for early diagnosis and progression of AD. Methods We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic Pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. Results Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic Pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. Conclusions The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.
Randy H Kardon - One of the best experts on this subject based on the ideXlab platform.
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Video_5_Buzzing Sympathetic Nerves: A New Test to Enhance Anisocoria in Horner's Syndrome.MP4
2019Co-Authors: Rawan Omary, Christopher Bockisch, Klara Landau, Randy H Kardon, Konrad P. WeberAbstract:Introduction: Patients with suspected Horner's syndrome having equivocal pupil dilation lag and pharmacologic testing may undergo unnecessary MR imaging and work up in the case of false positive pupil test results. Our goal was to increase the diagnostic accuracy of Pupillometry by accentuating the inter-ocular asymmetry of sympathetic innervation to the iris dilator with surface electrical stimulation of the median nerve using a standard electromyography machine. We hypothesized that an accentuated difference in sympathetic response between the two eyes would facilitate the diagnosis of Horner's syndrome.Methods: Eighteen patients with pharmacologically proven Horner's syndrome were compared to ten healthy volunteers tested before and after monocular instillation of 0.2% brimonidine tartrate ophthalmic solution to induce pharmacological Horner's syndrome. Pupillary responses were measured with binocular Pupillometry in response to sympathetic activation by electrical stimulation of the median nerve in darkness and at various times after extinction of a light stimulus. Sudomotor sympathetic responses from the palm of the stimulated arm were recorded simultaneously.Results: In subjects with Horner's syndrome and pharmacologically induced unilateral sympathetic deficit, electrical stimulation in combination with the extinction of light greatly enhanced the anisocoria during the evoked pupil dilation, while there was no significant increase in anisocoria in healthy subjects. The asymmetry of the sympathetic response was greatest when the electrical stimulus was given 2 s after termination of the light or under constant low light conditions. When given 2 s after termination of light, the electrical stimulation increased the mean anisocoria from 1.0 to 1.2 mm in Horner's syndrome (p = 0.01) compared to 0.22–0.26 mm in healthy subjects (p = 0.1). In all subjects, the maximal anisocoria induced by the electrical stimulation appeared within a 2 s interval after the stimulus. Correspondingly, the largest change in anisocoria between light and dark without electrical stimulation was seen between 3 and 4 s after light-off. While stronger triple stimulation further enhanced the anisocoria, it was less well tolerated.Conclusions: Electrical stimulation 2 s after light-off greatly enhances the sensitivity of Pupillometry for diagnosing Horner's syndrome. This new method may help to rule in or rule out a questionable Horner's syndrome, especially if the results of topical pharmacological testing are inconclusive.
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Buzzing Sympathetic Nerves: A New Test to Enhance Anisocoria in Horner's Syndrome
Frontiers Media S.A., 2019Co-Authors: Rawan Omary, Christopher Bockisch, Klara Landau, Randy H Kardon, Konrad P. WeberAbstract:Introduction: Patients with suspected Horner's syndrome having equivocal pupil dilation lag and pharmacologic testing may undergo unnecessary MR imaging and work up in the case of false positive pupil test results. Our goal was to increase the diagnostic accuracy of Pupillometry by accentuating the inter-ocular asymmetry of sympathetic innervation to the iris dilator with surface electrical stimulation of the median nerve using a standard electromyography machine. We hypothesized that an accentuated difference in sympathetic response between the two eyes would facilitate the diagnosis of Horner's syndrome.Methods: Eighteen patients with pharmacologically proven Horner's syndrome were compared to ten healthy volunteers tested before and after monocular instillation of 0.2% brimonidine tartrate ophthalmic solution to induce pharmacological Horner's syndrome. Pupillary responses were measured with binocular Pupillometry in response to sympathetic activation by electrical stimulation of the median nerve in darkness and at various times after extinction of a light stimulus. Sudomotor sympathetic responses from the palm of the stimulated arm were recorded simultaneously.Results: In subjects with Horner's syndrome and pharmacologically induced unilateral sympathetic deficit, electrical stimulation in combination with the extinction of light greatly enhanced the anisocoria during the evoked pupil dilation, while there was no significant increase in anisocoria in healthy subjects. The asymmetry of the sympathetic response was greatest when the electrical stimulus was given 2 s after termination of the light or under constant low light conditions. When given 2 s after termination of light, the electrical stimulation increased the mean anisocoria from 1.0 to 1.2 mm in Horner's syndrome (p = 0.01) compared to 0.22–0.26 mm in healthy subjects (p = 0.1). In all subjects, the maximal anisocoria induced by the electrical stimulation appeared within a 2 s interval after the stimulus. Correspondingly, the largest change in anisocoria between light and dark without electrical stimulation was seen between 3 and 4 s after light-off. While stronger triple stimulation further enhanced the anisocoria, it was less well tolerated.Conclusions: Electrical stimulation 2 s after light-off greatly enhances the sensitivity of Pupillometry for diagnosing Horner's syndrome. This new method may help to rule in or rule out a questionable Horner's syndrome, especially if the results of topical pharmacological testing are inconclusive
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assessment of rod cone and intrinsically photosensitive retinal ganglion cell contributions to the canine chromatic pupillary response
Investigative Ophthalmology & Visual Science, 2017Co-Authors: Randy H Kardon, Connie Y Yeh, Kristin Koehl, Christine D Harman, Simone Iwabe, Jose M Guzman, Simon M Petersenjones, Andras M KomaromyAbstract:Purpose The purpose of this study was to evaluate a chromatic Pupillometry protocol for specific functional assessment of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) in dogs. Methods Chromatic Pupillometry was tested and compared in 37 dogs in different stages of primary loss of rod, cone, and combined rod/cone and optic nerve function, and in 5 wild-type (WT) dogs. Eyes were stimulated with 1-s flashes of dim (1 cd/m2) and bright (400 cd/m2) blue light (for scotopic conditions) or bright red (400 cd/m2) light with 25-cd/m2 blue background (for photopic conditions). Canine retinal melanopsin/Opn4 was cloned, and its expression was evaluated using real-time quantitative reverse transcription-PCR and immunohistochemistry. Results Mean ± SD percentage of pupil constriction amplitudes induced by scotopic dim blue (scDB), scotopic bright blue (scBB), and photopic bright red (phBR) lights in WT dogs were 21.3% ± 10.6%, 50.0% ± 17.5%, and 19.4% ± 7.4%, respectively. Melanopsin-mediated responses to scBB persisted for several minutes (7.7 ± 4.6 min) after stimulus offset. In dogs with inherited retinal degeneration, loss of rod function resulted in absent scDB responses, followed by decreased phBR responses with disease progression and loss of cone function. Primary loss of cone function abolished phBR responses but preserved those responses to blue light (scDB and scBB). Although melanopsin/Opn4 expression was diminished with retinal degeneration, melanopsin-expressing ipRGCs were identified for the first time in both WT and degenerated canine retinas. Conclusions Pupil responses elicited by light stimuli of different colors and intensities allowed differential functional assessment of canine rods, cones, and ipRGCs. Chromatic Pupillometry offers an effective tool for diagnosing retinal and optic nerve diseases.
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chromatic Pupillometry in patients with retinitis pigmentosa
Ophthalmology, 2011Co-Authors: Randy H Kardon, Susan C Anderson, Tina G Damarjian, Elizabeth M Grace, Edwin M Stone, Aki KawasakiAbstract:OBJECTIVE: To evaluate the chromatic pupillary response as a means of assessing outer and inner retinal function in patients with retinitis pigmentosa (RP).DESIGN: Evaluation of diagnostic technolo ...
Giulia Amore - One of the best experts on this subject based on the ideXlab platform.
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correction Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep wake activity in pre symptomatic alzheimer s disease
PLOS ONE, 2019Co-Authors: Angela J Oh, Giulia Amore, William Sultan, Samuel Asanad, Jason C Park, Martina Romagnoli, Chiara La Morgia, Rustum Karanjia, Michael G Harrington, Alfredo A SadunAbstract:BACKGROUND: Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body's circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer's disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic Pupillometry may be a potential biomarker for early diagnosis and progression of AD. METHODS: We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic Pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. RESULTS: Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic Pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. CONCLUSIONS: The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.
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Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep wake activity in pre symptomatic alzheimer s disease
PLOS ONE, 2019Co-Authors: Giulia Amore, William Sultan, Samuel Asanad, Jason C Park, Martina Romagnoli, Chiara La Morgia, Rustum Karanjia, Michael G Harrington, Alfredo A SadunAbstract:Background Melanopsin-expressing retinal ganglion cells (mRGCs), intrinsically photosensitive RGCs, mediate the light-based pupil response and the light entrainment of the body’s circadian rhythms through their connection to the pretectal nucleus and hypothalamus, respectively. Increased awareness of circadian rhythm dysfunction in neurological conditions including Alzheimer’s disease (AD), has led to a wave of research focusing on the role of mRGCs in these diseases. Postmortem retinal analyses in AD patients demonstrated a significant loss of mRGCs, and in vivo measurements of mRGC function with chromatic Pupillometry may be a potential biomarker for early diagnosis and progression of AD. Methods We performed a prospective case-control study in 20 cognitively healthy study participants: 10 individuals with pre-symptomatic AD pathology (pre-AD), identified by the presence of abnormal levels of amyloid β42 and total Tau proteins in the cerebrospinal fluid, and 10 age-matched controls with normal CSF amyloid β42 and Tau levels. To evaluate mRGC function, we used a standardized protocol of chromatic Pupillometry on a Ganzfeld system using red (640 nm) and blue (450 nm) light stimuli and measured the pupillary light response (PLR). Non-invasive wrist actigraphy and standardized sleep questionnaires were also completed to evaluate rest-activity circadian rhythm. Results Our results did not demonstrate a significant difference of the PLR between pre-AD and controls but showed a variability of the PLR in the pre-AD group compared with controls on chromatic Pupillometry. Wrist actigraphy showed variable sleep-wake patterns and irregular circadian rhythms in the pre-AD group compared with controls. Conclusions The variability seen in measurements of mRGC function and sleep-wake cycle in the pre-AD group suggests that mRGC dysfunction occurs in the pre-symptomatic AD stages, preceding cognitive decline. Future longitudinal studies following progression of these participants can help in elucidating the relationship between mRGCs and circadian rhythm dysfunction in AD.
