Abnormal pupillary light reflex with chromatic pupillometry in
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            aucher disease

Narita, Aya; Shirai, Kentarou; Kubota, Norika; Takayama, Rumiko; Takahashi, Yukitoshi; Onuki, Takanori; Numakura, Chikahiko; Kato, Mitsuhiro; Hamada, Yusuke; Sakai, Norio; Ohno, Akihiko; Asami, Maya; Matsushita, Shoko; Hayashi, Akira; Kumada, Takatsune; Fujii, Tatsuya; Horino, Asako; Inoue, Takeshi; Kuki, Ichiro; Asakawa, Ken; Ishikawa, Hitoshi; Ohno, Kiyotaka; Nishimura, Yoko; Tamasaki, Akiko; Maegaki, Yoshihiro; Ohno, Kousaku

doi:10.1002/acn3.33

Cited by 15 publications

(9 citation statements)

References 19 publications

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“…Chaperones can cross the blood-brain barrier and selectively bind to misfolded glucocerebrosidases facilitating the correction of protein misfolding and improving enzyme function. A recent pilot study investigating the efficacy of PCT in patients with Type III GD reported marked improvements in saccadic initiation latency and pupillary light reflex dysfunction107 using chromatic pupillometry device 108. Future studies should evaluate the efficacy of PCT in treating ophthalmic manifestations of GD.…”

Section: Discussionmentioning

confidence: 99%

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder

et al. 2019

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Gaucher disease (GD) results from a deficiency of glucocerebrosidase activity and the subsequent accumulation of the enzyme’s metabolites, principally glucosylsphingosine and glucosylceramide. There are three principal forms: Type I, which is the most common, is usually considered non-neuronopathic. Type II, III and IIIc manifest earlier and have neurological sequelae due to markedly reduced enzyme activity. Gaucher’s can be associated with ophthalmological sequelae but these have not been systematically reviewed. We therefore performed a comprehensive literature review of all such ophthalmic abnormalities associated with the different types of Gaucher disease. We systematically searched the literature (1950 – present) for functional and structural ocular abnormalities arising in patients with Gaucher disease and found that all subtypes can be associated with ophthalmic abnormalities; these range from recently described intraocular lesions to disease involving the adnexae, peripheral nerves and brain. In summary, Gaucher can affect most parts of the eye. Rarely is it sight-threatening; some but not all manifestations are amenable to treatment, including with enzyme replacement and substrate reduction therapy. Retinal involvement is rare but patients with ocular manifestations should be monitored and treated early to reduce the risk of progression and further complications. As Gaucher disease is also associated with Parkinsons disease and may also confer an increased risk of malignancy (particularly haematological forms and melanoma), any ocular abnormalities should be fully investigated to exclude these potential underlying conditions.

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Section: Discussionmentioning

confidence: 99%

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder

et al. 2019

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“…Changes in the myoclonus scores with action, functional tests, and stimulus sensitivity were evaluated in patients who could follow the instructions. PLR was assessed in all patients using an infrared pupillometer, as reported in an earlier study . In this study, we selected a 1‐s red stimulus of 270 cd/m 2 and evaluated the mean values of the initial constriction rate and latency.…”

Section: Methodsmentioning

confidence: 99%

Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study

Narita

Shirai

Itamura

et al. 2016

Ann Clin Transl Neurol

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170

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ObjectiveGaucher disease (GD) is a lysosomal storage disease characterized by a deficiency of glucocerebrosidase. Although enzyme‐replacement and substrate‐reduction therapies are available, their efficacies in treating the neurological manifestations of GD are negligible. Pharmacological chaperone therapy is hypothesized to offer a new strategy for treating the neurological manifestations of this disease. Specifically, ambroxol, a commonly used expectorant, has been proposed as a candidate pharmacological chaperone. The purpose of this study was to evaluate the safety, tolerability, and neurological efficacy of ambroxol in patients with neuronopathic GD.MethodsThis open‐label pilot study included five patients who received high‐dose oral ambroxol in combination with enzyme replacement therapy. Safety was assessed by adverse event query, physical examination, electrocardiography, laboratory studies, and drug concentration. Biochemical efficacy was assessed through evidence of glucocerebrosidase activity in the lymphocytes and glucosylsphingosine levels in the cerebrospinal fluid. Neurological efficacy was evaluated using the Unified Myoclonus Rating Scale, Gross Motor Function Measure, Functional Independence Measure, seizure frequency, pupillary light reflex, horizontal saccadic latency, and electrophysiologic studies.ResultsHigh‐dose oral ambroxol had good safety and tolerability, significantly increased lymphocyte glucocerebrosidase activity, permeated the blood–brain barrier, and decreased glucosylsphingosine levels in the cerebrospinal fluid. Myoclonus, seizures, and pupillary light reflex dysfunction markedly improved in all patients. Relief from myoclonus led to impressive recovery of gross motor function in two patients, allowing them to walk again.InterpretationPharmacological chaperone therapy with high‐dose oral ambroxol shows promise in treating neuronopathic GD, necessitating further clinical trials.

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“…In the experiment, a long wavelength (635 ± 5 nm) red light and a short wavelength (470 ± 7 nm) blue light were used at two different light intensities (10 and 100 cd/ m 2 ). The light stimulation conditions were adjusted in accordance with the method of Kawasaki and Kardon [ 10 ],[ 12 ] while the measurement validity was also confirmed [ 30 ],[ 31 ]. PLRs for light stimuli were simply recorded as single trial measure.…”

Section: Methodsmentioning

confidence: 99%

Discovering irregular pupil light responses to chromatic stimuli using waveform shapes of pupillograms

Nakayama

Nowak

Ishikawa

et al. 2014

J Bioinform Sys Biology

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BackgroundThe waveforms of the pupillary light reflex (PLR) can be analyzed in a diagnostic test that allows for differentiation between disorders affecting photoreceptors and disorders affecting retinal ganglion cells, using various signal processing techniques. This procedure has been used on both healthy subjects and patients with age-related macular degeneration (AMD), as a simple diagnostic procedure is required for diagnosis.ResultsThe Fourier descriptor technique is used to extract the features of PLR waveform shapes of pupillograms and their amplitudes. To detect those patients affected by AMD using the extracted features, multidimensional scaling (MDS) and clustering techniques were used to emphasize stimuli and subject differences. The detection performance of AMD using the features and the MDS technique shows only a qualitative tendency, however. To evaluate the detection performance quantitatively, a set of combined features was created to evaluate characteristics of the PLR waveform shapes in detail. Classification performance was compared across three categories (AMD patients, aged, and healthy subjects) using the Random Forest method, and weighted values were optimized using variations of the classification error rates. The results show that the error rates for healthy pupils and AMD-affected pupils were low when the value of the coefficient for a combination of PLR amplitudes and features of waveforms was optimized as 1.5. However, the error rates for patients with age-affected eyes was not low.ConclusionsA classification procedure for AMD patients has been developed using the features of PLR waveform shapes and their amplitudes. The results show that the error rates for healthy PLRs and AMD PLRs were low when the Random Forest method was used to produce the classification. The classification of pupils of patients with age-affected eyes should be carefully considered in order to produce optimum results.Electronic supplementary materialThe online version of this article (doi:10.1186/s13637-014-0018-x) contains supplementary material, which is available to authorized users.

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Abnormal pupillary light reflex with chromatic pupillometry in G aucher disease

Cited by 15 publications

References 19 publications

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder

Ophthalmic manifestations of Gaucher disease: the most common lysosomal storage disorder

Ambroxol chaperone therapy for neuronopathic Gaucher disease: A pilot study

Discovering irregular pupil light responses to chromatic stimuli using waveform shapes of pupillograms

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