Multiethnic involvement in autosomal-dominant optic atrophy in Singapore

Loo, Jenny Hooi Yin; Singhal, Shweta; Rukmini, Annadata; Tow, Sharon; Amati-Bonneau, P.; Procaccio, Vincent; Bonneau, Dominique; Gooley, Joshua J.; Reynier, Pascal; Ferré, Marc; Miléa, Dan

doi:10.1038/eye.2016.255

Cited by 10 publications

(8 citation statements)

References 34 publications

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“…Hence, ipRGC dysfunction or cell loss can be detected in early stages of glaucoma and is associated with structural correlates of disease progression. In another study that used the ramp-up light protocol, patients with autosomal-dominant optic atrophy ( n = 5) showed pupillary responses that were comparable to healthy controls (96), which is consistent with other studies that have found preserved ipRGC function in mitochondrial disease (77).…”

Section: Chromatic Pupillometry Methods For Assessing Retinal and Optsupporting

confidence: 86%

Chromatic Pupillometry Methods for Assessing Photoreceptor Health in Retinal and Optic Nerve Diseases

2019

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The pupillary light reflex is mediated by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs), which also receive input from rods and cones. Melanopsin-dependent pupillary light responses are short-wavelength sensitive, have a higher threshold of activation, and are much slower to activate and de-activate compared with rod/cone-mediated responses. Given that rod/cone photoreceptors and melanopsin differ in their response properties, light stimuli can be designed to stimulate preferentially each of the different photoreceptor types, providing a read-out of their function. This has given rise to chromatic pupillometry methods that aim to assess the health of outer retinal photoreceptors and ipRGCs by measuring pupillary responses to blue or red light stimuli. Here, we review different types of chromatic pupillometry protocols that have been tested in patients with retinal or optic nerve disease, including approaches that use short-duration light exposures or continuous exposure to light. Across different protocols, patients with outer retinal disease (e.g., retinitis pigmentosa or Leber congenital amaurosis) show reduced or absent pupillary responses to dim blue-light stimuli used to assess rod function, and reduced responses to moderately-bright red-light stimuli used to assess cone function. By comparison, patients with optic nerve disease (e.g., glaucoma or ischemic optic neuropathy, but not mitochondrial disease) show impaired pupillary responses during continuous exposure to bright blue-light stimuli, and a reduced post-illumination pupillary response after light offset, used to assess melanopsin function. These proof-of-concept studies demonstrate that chromatic pupillometry methods can be used to assess damage to rod/cone photoreceptors and ipRGCs. In future studies, it will be important to determine whether chromatic pupillometry methods can be used for screening and early detection of retinal and optic nerve diseases. Such methods may also prove useful for objectively evaluating the degree of recovery to ipRGC function in blind patients who undergo gene therapy or other treatments to restore vision.

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Section: Chromatic Pupillometry Methods For Assessing Retinal and Optsupporting

confidence: 86%

Chromatic Pupillometry Methods for Assessing Photoreceptor Health in Retinal and Optic Nerve Diseases

2019

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“…The reasons for the robustness of mRGCs in mitochondrial optic neuropathies are still unknown and under investigation, even though the possible role of peculiar metabolic properties, including the size of the soma, has been proposed (50, 52, 53). More recently, pupillometric studies showed a relative maintenance of the mRGC-mediated pupil response in LHON and DOA patients (24–29) (Table 2). Similarly to the maintenance of the PLR a preserved light-induced melatonin suppression has been demonstrated in LHON and DOA patients supporting a relative preservation of these cells in hereditary mitochondrial optic neuropathies (50).…”

Section: Melanopsin Rgcs and Pupil In Hereditary Mitochondrial Optic mentioning

confidence: 93%

“…The PLR mediated by mRGCs has been investigated in different ophthalmological conditions including glaucoma (16–18), retinitis pigmentosa (19), diabetes (20), Leber's congenital amaurosis (14), age-related macular degeneration (21), and ischemic optic neuropathies (22, 23). Moreover, various neurological and psychiatric disorders have been evaluated, including hereditary optic neuropathies (24–29), seasonal affective disorder (SAD) (30), idiopathic intracranial hypertension (IIH) (31, 32), multiple sclerosis (MS) (33), and Parkinson's disease (PD) (34).…”

Section: Introductionmentioning

confidence: 99%

Melanopsin Retinal Ganglion Cells and Pupil: Clinical Implications for Neuro-Ophthalmology

2018

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Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive RGCs that mediate many relevant non-image forming functions of the eye, including the pupillary light reflex, through the projections to the olivary pretectal nucleus. In particular, the post-illumination pupil response (PIPR), as evaluated by chromatic pupillometry, can be used as a reliable marker of mRGC function in vivo. In the last years, pupillometry has become a promising tool to assess mRGC dysfunction in various neurological and neuro-ophthalmological conditions. In this review we will present the most relevant findings of pupillometric studies in glaucoma, hereditary optic neuropathies, ischemic optic neuropathies, idiopathic intracranial hypertension, multiple sclerosis, Parkinson's disease, and mood disorders. The use of PIPR as a marker for mRGC function is also proposed for other neurodegenerative disorders in which circadian dysfunction is documented.

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“…In primary open angle glaucoma, a condition associated with histological mRGC loss (63), abnormal melatonin secretion profile (64) and sleep and circadian rhythm dysfunction (65), various pupillometric studies have shown abnormal PLR responses (28, 66–70). Conversely, in mitochondrial hereditary optic neuropathies, mRGCs are resistant to neurodegeneration, explaining the relatively preserved chromatic pupillometry parameters (71–73) and melatonin profiles (74). It is possible that mRGC loss, alone or combined with neuronal loss occurring in the suprachiasmatic nuclei, may be associated with circadian rhythm dysfunctions which can occur even at early stages of AD (3, 5).…”

Section: Pathophysiology Of Light-induced Pupillary Responses In Admentioning

confidence: 99%

Light-Induced Pupillary Responses in Alzheimer's Disease

et al. 2019

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The impact of Alzheimer's disease (AD) on the pupillary light response (PLR) is controversial, being dependent on the stage of the disease and on the experimental pupillometric protocols. The main hypothesis driving pupillometry research in AD is based on the concept that the AD-related neurodegeneration affects both the parasympathetic and the sympathetic arms of the PLR (cholinergic and noradrenergic theory), combined with additional alterations of the afferent limb, involving the melanopsin expressing retinal ganglion cells (mRGCs), subserving the PLR. Only a few studies have evaluated the value of pupillometry as a potential biomarker in AD, providing various results compatible with parasympathetic dysfunction, displaying increased latency of pupillary constriction to light, decreased constriction amplitude, faster redilation after light offset, decreased maximum velocity of constriction (MCV) and maximum constriction acceleration (MCA) compared to controls. Decreased MCV and MCA appeared to be the most accurate of all PLR parameters allowing differentiation between AD and healthy controls while increased post-illumination pupillary response was the most consistent feature, however, these results could not be replicated by more recent studies, focusing on early and pre-clinical stages of the disease. Whether static or dynamic pupillometry yields useful biomarkers for AD screening or diagnosis remains unclear. In this review, we synopsize the current knowledge on pupillometric features in AD and other neurodegenerative diseases, and discuss potential roles of pupillometry in AD detection, diagnosis and monitoring, alone or in combination with additional biomarkers.

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Multiethnic involvement in autosomal-dominant optic atrophy in Singapore

Cited by 10 publications

References 34 publications

Chromatic Pupillometry Methods for Assessing Photoreceptor Health in Retinal and Optic Nerve Diseases

Chromatic Pupillometry Methods for Assessing Photoreceptor Health in Retinal and Optic Nerve Diseases

Melanopsin Retinal Ganglion Cells and Pupil: Clinical Implications for Neuro-Ophthalmology

Light-Induced Pupillary Responses in Alzheimer's Disease

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