Yijun Huang

J Clin Invest. 2019 Feb 1;129(2):863-874. doi: 10.1172/JCI123980. Epub 2019 Jan 22.

ABSTRACT

Inherited retinal degenerations are a common cause of untreatable blindness worldwide, with retinitis pigmentosa and cone dystrophy affecting approximately 1 in 3500 and 1 in 10,000 individuals, respectively. A major limitation to the development of effective therapies is the lack of availability of animal models that fully replicate the human condition. Particularly for cone disorders, rodent, canine, and feline models with no true macula have substantive limitations. By contrast, the cone-rich macula of a nonhuman primate (NHP) closely mirrors that of the human retina. Consequently, well-defined NHP models of heritable retinal diseases, particularly cone disorders that are predictive of human conditions, are necessary to more efficiently advance new therapies for patients. We have identified 4 related NHPs at the California National Primate Research Center with visual impairment and findings from clinical ophthalmic examination, advanced retinal imaging, and electrophysiology consistent with achromatopsia. Genetic sequencing confirmed a homozygous R565Q missense mutation in the catalytic domain of PDE6C, a cone-specific phototransduction enzyme associated with achromatopsia in humans. Biochemical studies demonstrate that the mutant mRNA is translated into a stable protein that displays normal cellular localization but is unable to hydrolyze cyclic GMP (cGMP). This NHP model of a cone disorder will not only serve as a therapeutic testing ground for achromatopsia gene replacement, but also for optimization of gene editing in the macula and of cone cell replacement in general.

PMID:30667376 | PMC:PMC6355306 | DOI:10.1172/JCI123980

Invest Ophthalmol Vis Sci. 2013 Jul 2;54(7):4512-8. doi: 10.1167/iovs.13-12265.

ABSTRACT

PURPOSE: To investigate the effect of optical coherence tomography macular grid displacement on retinal thickness measurements.

METHODS: SD-OCT macular scans of 66 eyes with various retinal thicknesses were selected. Decentration of the 1-, 3-, 6-mm-diameter macular grid was simulated by manually adjusting the distance between center of the fovea (cFovea) and center of the grid (cGrid). Center subfield thickness (CSF) between the internal limiting membrane and the top of the retinal pigment epithelium was measured along the displacement distance where the grid was displaced in eight cardinal directions from the cFovea in steps of 100 μm within the central 1-mm subfield and then by 200 μm within the inner subfields. One-way/mixed-effects repeated-measures ANOVA models were used to determine changes of CSF (ΔCSF) as a function of displacement distance (for α = 0.05, power = 0.80 and effect size = 0.1). The interactions between the displacement distance and direction, center point thickness (CPT), and foveal contour were also analyzed.

RESULTS: The CSF measurement showed statistically significant error when the displacement distance between cFovea and cGrid exceeded 200 μm. The direction of displacement did not affect the ΔCSF-distance relationship, while the CPT and foveal contour significantly affected the relationship, in that some subgroups showed slightly larger tolerance in the displacement distance up to 300 μm before reaching significant ΔCSF.

CONCLUSIONS: Small displacement distances of the macular grid from the cFovea affect CSF measurements throughout a broad range of thicknesses and retinal contour alterations from disease. Accurate registration of OCT scans or post hoc repositioning of the grid is essential to optimize CSF accuracy.

PMID:23761091 | PMC:PMC3700389 | DOI:10.1167/iovs.13-12265

Invest Ophthalmol Vis Sci. 2012 Apr 24;53(4):2133-41. doi: 10.1167/iovs.11-8755.

ABSTRACT

PURPOSE: The purpose of this article was to assess signal quality of retinal optical coherence tomography (OCT) images from multiple devices using subjective and quantitative measurements.

METHODS: A total of 120 multiframe OCT images from 4 spectral domain OCT devices (Cirrus, RTVue, Spectralis, and 3D OCT-1000) were evaluated subjectively by trained graders, and measured quantitatively using a derived parameter, maximum tissue contrast index (mTCI). An intensity histogram decomposition model was proposed to separate the foreground and background information of OCT images and to calculate the mTCI. The mTCI results were compared with the manufacturer signal index (MSI) provided by the respective devices, and to the subjective grading scores (SGS).

RESULTS: Statistically significant correlations were observed between the paired methods (i.e., SGS and MSI, SGS and mTCI, and mTCI and MSI). Fisher's Z transformation indicated the Pearson correlation coefficient ρ ≥ 0.8 for all devices. Using the Deming regression, correlation parameters between the paired methods were established. This allowed conversion from the proprietary MSI values to SGS and mTCI that are universally applied to each device.

CONCLUSIONS: The study suggests signal quality of retinal OCT images can be evaluated subjectively and objectively, independent of the devices. Together with the proposed histogram decomposition model, mTCI may be used as a standardization metric for OCT signal quality that would affect measurements.

PMID:22427567 | PMC:PMC3995569 | DOI:10.1167/iovs.11-8755