Dataset Information

Short-Wavelength Sensitive Cone (S-cone) Testing as an Outcome Measure for NR2E3 Clinical Treatment Trials.

ABSTRACT: Recessively-inherited NR2E3 gene mutations cause an unusual retinopathy with abnormally-increased short-wavelength sensitive cone (S-cone) function, in addition to reduced rod and long/middle-wavelength sensitive cone (L/M-cone) function. Progress toward clinical trials to treat patients with this otherwise incurable retinal degeneration prompted the need to determine efficacy outcome measures. Comparisons were made between three computerized perimeters available in the clinic. These perimeters could deliver short-wavelength stimuli on longer-wavelength adapting backgrounds to measure whether S-cone vision can be quantified. Results from a cohort of normal subjects were compared across the three perimeters to determine S-cone isolation and test-retest variability. S-cone perimetry data from NR2E3-ESCS (enhanced S-cone syndrome) patients were examined and determined to have five stages of disease severity. Using these stages, strategies were proposed for monitoring efficacy of either a focal or retina-wide intervention. This work sets the stage for clinical trials.

SUBMITTER: Roman AJ

PROVIDER: S-EPMC6566804 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Short-Wavelength Sensitive Cone (S-cone) Testing as an Outcome Measure for <i>NR2E3</i> Clinical Treatment Trials.

Roman Alejandro J AJ Powers Christian A CA Semenov Evelyn P EP Sheplock Rebecca R Aksianiuk Valeryia V Russell Robert C RC Sumaroka Alexander A Garafalo Alexandra V AV Cideciyan Artur V AV Jacobson Samuel G SG

International journal of molecular sciences 20190521 10

Recessively-inherited <i>NR2E3</i> gene mutations cause an unusual retinopathy with abnormally-increased short-wavelength sensitive cone (S-cone) function, in addition to reduced rod and long/middle-wavelength sensitive cone (L/M-cone) function. Progress toward clinical trials to treat patients with this otherwise incurable retinal degeneration prompted the need to determine efficacy outcome measures. Comparisons were made between three computerized perimeters available in the clinic. These peri ...[more]

PMID: 31117170

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Project description: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.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-s 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.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 three of four 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.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.

Dataset Information

Short-Wavelength Sensitive Cone (S-cone) Testing as an Outcome Measure for NR2E3 Clinical Treatment Trials.

Publications

Short-Wavelength Sensitive Cone (S-cone) Testing as an Outcome Measure for <i>NR2E3</i> Clinical Treatment Trials.

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