Full-Field Pupillary Light Responses, Luminance Thresholds, and Light Discomfort Thresholds in<i>CEP290</i>Leber Congenital Amaurosis Patients

Collison, Frederick T; Park, Jason C; Fishman, Gerald A.; McAnany, J. Jason; Stone, Edwin M.

doi:10.1167/iovs.15-17467

Cited by 28 publications

(32 citation statements)

References 31 publications

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“…21 The use of alternative methods of cone isolation will help answer this important question. [47][48][49] The reliability of the sensitivity estimates in this group of young patients was also considered. Normal age-related changes in rod sensitivity may not be expected to occur in children within the age range represented in this study.…”

Section: Discussionmentioning

confidence: 99%

RDH12Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function

Alemán

Uyhazi

Serrano

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To describe the retinal phenotype of pediatric patients with mutations in the retinol dehydrogenase 12 (RDH12) gene. METHODS. Twenty-one patients from 14 families (ages 2-17 years) with RDH12-associated inherited retinal degeneration (RDH12-IRD) underwent a complete ophthalmic exam and imaging with spectral domain optical coherence tomography (SD-OCT) and near infrared and short-wavelength fundus autofluorescence. Visual field extent was measured with Goldmann kinetic perimetry, visual thresholds with dark-adapted static perimetry or with dark-adapted chromatic full-field stimulus testing (FST) and transient pupillometry. RESULTS. Visual acuity ranged from 20/40 to light perception. There was parafoveal depigmentation or atrophic maculopathies accompanied by midperipheral intraretinal pigment migration. SD-OCT revealed foveal thinning in all patients and detectable but thinned outer nuclear layer (ONL) at greater eccentricities from the fovea. Photoreceptor outer segment (POS) signals were only detectable in small pockets within the central retina. Measurable kinetic visual fields were limited to small (<5-108) central islands of vision. Electroretinograms were reported as undetectable or severely reduced in amplitude. FST sensitivities to a 467 nm stimulus were rod-mediated and reduced on average by~2.5 log units. A thinned central ONL colocalized with severely reduced to nondetectable conemediated sensitivities. Pupillometry confirmed the psychophysically measured abnormalities. CONCLUSIONS. RDH12-IRD causes an early-onset, retina-wide disease with particularly severe central retinal abnormalities associated with relatively less severe rod photoreceptor dysfunction, a pattern consistent with an early-onset cone-rod dystrophy. Severely abnormal POS but detectable ONL in the pericentral and peripapillary retina suggest these regions may become targets for gene therapy.

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Section: Discussionmentioning

confidence: 99%

RDH12Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function

Alemán

Uyhazi

Serrano

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…17,25 A non-recordable rod-mediated PLR has also been shown in some patients with Leber congenital amaurosis, but these patients typically have substantially reduced cone-mediated PLRs as well. 17,26 Thus, while two-color pupillometry could have clinical value in ESCS (e.g. in a child, who may be uncooperative for ERG, with atypical ESCS fundus findings 11,27,28,29 ), distinguishing among patients with RP and ESCS may be difficult on the basis of the PLR alone.…”

Section: Discussionmentioning

confidence: 99%

Two-color pupillometry in enhanced S-cone syndrome caused by NR2E3 mutations

et al. 2016

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Purpose: The purpose of this study was to evaluate pupillary light reflexes (PLRs) mediated by rod, cone, and intrinsically photosensitive retinal ganglion cell pathways as indices of outer- and inner-retinal function in patients who have enhanced S-cone syndrome (ESCS) due to NR2E3 mutations. Methods: Four patients with ESCS (ages 16-23 years) participated in the study. Subjects were tested with long- and short-wavelength single-flash full-field ERG stimuli under light adapted conditions. They were also tested with an established pupillometry protocol involving 1-second duration, long- and short-wavelength stimuli under dark- and light-adapted conditions. The PLR was measured as a function of stimulus luminance. Transient PLRs were measured under all conditions, and sustained PLRs were measured under the highest luminance dark-adapted condition. Results: Two-color light-adapted full-field ERGs demonstrated larger amplitude responses for short-wavelength stimuli relative to long-wavelength stimuli of the same photopic luminance, with 3 of 4 ESCS patients having super-normal a-wave amplitudes to the short-wavelength stimulus. B/A wave ratios were reduced in all four cases. Transient PLRs elicited by low luminance stimuli under dark-adapted conditions (rod-mediated) were unrecordable, whereas the sustained PLRs elicited by high luminance stimuli (melanopsin-mediated) were normal. Cone-mediated PLRs were recordable for all four patients, but generally lower than normal in amplitude. However, the cone-mediated PLR was larger for the short-wavelength stimulus compared to the photopically matched long-wavelength stimulus at high luminances, a pattern that was not observed for control subjects. None of the PLR conditions demonstrated “super-normal” responses. Conclusions: ESCS patients appear to have generally well-preserved cone- and melanopsin-mediated PLRs, indicating intact inner-retinal function. Two-color pupillometry demonstrates greater sensitivity to short-wavelength light under higher-luminance conditions and could complement the ERG as a tool for evaluating retinal function in ESCS.

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“…Relatively recent advances in the understanding of the neural mechanisms that mediate the pupil response have greatly renewed interest in pupillometry as a tool for assessing retinal function in patients with acquired91011 and inherited12131415 retinal disease. That is, the afferent limb of the pupillary response to light is now thought to be driven primarily by intrinsically photosensitive retinal ganglion cells (ipRGCs) that contain the photopigment melanopsin1617.…”

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confidence: 99%

Pupillary responses in non-proliferative diabetic retinopathy

Park

Chen

Blair

et al. 2017

Sci Rep

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The goal of this study was to determine the extent of rod-, cone-, and melanopsin-mediated pupillary light reflex (PLR) abnormalities in diabetic patients who have non-proliferative diabetic retinopathy (NPDR). Fifty diabetic subjects who have different stages of NPDR and 25 age-equivalent, non-diabetic controls participated. PLRs were measured in response to full-field, brief-flash stimuli under conditions that target the rod, cone, and intrinsically-photosensitive (melanopsin) retinal ganglion cell pathways. Pupil responses were compared among the subjects groups using age-corrected linear mixed models. Compared to control, the mean baseline pupil diameters were significantly smaller for all patient groups in the dark (all p < 0.001) and for the moderate-severe NPDR group in the light (p = 0.003). Pairwise comparisons indicated: (1) the mean melanopsin-mediated PLR was significantly reduced in the mild and moderate-severe groups (both p < 0.001); (2) the mean cone-mediated PLR was reduced significantly in the moderate-severe group (p = 0.008); (3) no significant differences in the mean rod-mediated responses. The data indicate abnormalities in NPDR patients under conditions that separately assess pupil function driven by different photoreceptor classes. The results provide evidence for compromised neural function in these patients and provide a promising approach for quantifying their neural abnormalities.

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Full-Field Pupillary Light Responses, Luminance Thresholds, and Light Discomfort Thresholds inCEP290Leber Congenital Amaurosis Patients

Cited by 28 publications

References 31 publications

RDH12Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function

RDH12Mutations Cause a Severe Retinal Degeneration With Relatively Spared Rod Function

Two-color pupillometry in enhanced S-cone syndrome caused by NR2E3 mutations

Pupillary responses in non-proliferative diabetic retinopathy

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