Dr. Huang earned his Ph.D. in bioengineering from University of Pennsylvania and is currently a Senior Scientist in the Department of Ophthalmology and Visual Sciences at University of Wisconsin-Madison. He is co-director of the Fundus Photograph Reading Center, UW-Madison and co-founder and Chief Technology Officer for EyeKor. Dr. Huang has 15 years experience in developing software and hardware imaging solutions for ophthalmic imaging applications both in academic and industrial environments. Dr. Huang's research interests include evaluating and developing technologies relating to ophthalmic imaging and analysis (e.g., computerized disease detection, classification, and monitoring), and using them to gain insights into disease progression and treatment effects in large-scale multi-center clinical trials.
Quantification of Geographic Atrophy Using Spectral Domain OCT in Age-Related Macular Degeneration
Ophthalmol Retina. 2021 Jan;5(1):41-48. doi: 10.1016/j.oret.2020.07.006. Epub 2020 Jul 15.
PURPOSE: To compare geographic atrophy (GA) area and enlargement rate measured with spectral domain OCT (SD-OCT) with fundus autofluorescence (FAF), color fundus photography (CFP), and infrared reflectance (IR) imaging.
DESIGN: Retrospective, multicenter, natural history case series.
PARTICIPANTS: A total of 70 eyes with GA from 48 participants were included.
METHODS: Participants underwent SD-OCT, FAF, CFP, and IR imaging at baseline and 12 months in the study eye. Spectral domain OCT images were graded for GA area using 2 distinct criteria: (1) complete retinal pigment epithelium and outer retinal atrophy (cRORA) and (2) hypertransmission through Bruch's membrane. Areas were measured with SD-OCT using a custom-developed tool that allows for mapping areas of retinal layer loss on SD-OCT cross-sectional scans with co-registered IR images. Circularity index was calculated from area and perimeter. Spectral domain OCT images were also assessed for presence of reticular pseudodrusen, outer-retinal tubules, and hyporeflective wedge-shaped bands. Area of GA was measured in millimeters squared from FAF, CFP, and IR images.
MAIN OUTCOME MEASURES: Geographic atrophy mean baseline area and enlargement rate measured with 2 SD-OCT criteria, FAF, CFP, and IR.
RESULTS: At baseline, the mean GA area was 6.9 (standard deviation [SD], 4.7) mm2 using the SD-OCT cRORA criteria and 7.3 (SD, 4.7) mm2 using the SD-OCT hypertransmission criteria. The mean annual enlargement rate of GA was 1.6 (SD, 1.1) mm2 using the SD-OCT cRORA criteria and 1.5 (SD, 1.0) mm2 using the SD-OCT hypertransmission criteria. When comparing both SD-OCT grading criteria with FAF, CFP, and IR, there were no statistically significant differences in baseline area or annual enlargement rate of GA. Circularity index was identified as the risk factor for increased annual enlargement rate.
CONCLUSIONS: Measuring GA using retinal layer morphology provides a novel means of obtaining area measurements. Area measurements tend to vary based on criteria used and are comparable to other imaging modalities.
A nonhuman primate model of inherited retinal disease
J Clin Invest. 2019 Feb 1;129(2):863-874. doi: 10.1172/JCI123980. Epub 2019 Jan 22.
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.
Variability in Spectral-Domain Optical Coherence Tomography over 4 Weeks by Age
Ophthalmic Epidemiol. 2016 Jun;23(3):193-201. doi: 10.3109/09286586.2015.1119285. Epub 2016 Apr 29.
PURPOSE: To quantify variation in spectral-domain optical coherence tomography (SD-OCT) measures of total retinal thickness (top of inner limiting membrane to top of retinal pigment epithelium, RPE) and RPE thickness measures over a 4-week period and by age.
METHODS: A total of 76 volunteers aged 40-85 years were seen at three visits over 4 weeks. Two Topcon SD-OCT scans were taken at each visit. Following grid re-centration, total retinal and RPE thickness were determined in nine subfields. Multilevel modeling was used to quantify variance between scans and by age.
RESULTS: In the central circle, mean total retinal thickness was 237.9 µm (standard deviation, SD, 23.5 µm) and RPE thickness was 46.0 µm (SD 5.3 µm). Intraclass correlation coefficient in the central circle was 0.988 for total retinal thickness and 0.714 for RPE thickness. Pairwise measures taken within 4 weeks were strongly correlated (p > 0.95). Within-subject variation of total retinal thickness increased significantly with age. Subjects in the oldest age group had significantly increased among- and within-subject variability in measures of RPE thickness.
CONCLUSIONS: Correlation between retinal thickness measures was very high (>0.95) over a period of 4 weeks with small changes likely due to variation in measurement. Increasing variability in total retinal and RPE thickness measures with age suggest that the use of more and/or higher quality images to calculate mean thickness to reduce variability may benefit the study of these measures in older persons. This may also impact sample size calculations for future studies of SD-OCT measures in older adults.
The epidemiology of vitreoretinal interface abnormalities as detected by spectral-domain optical coherence tomography: the beaver dam eye study
Ophthalmology. 2015 Apr;122(4):787-95. doi: 10.1016/j.ophtha.2014.10.014. Epub 2014 Dec 31.
PURPOSE: To describe the prevalence and interrelationships of epiretinal membranes (ERMs), vitreomacular traction (VMT), macular cysts, paravascular cysts (PVCs), lamellar macular holes (LMHs), full-thickness macular holes (FTMHs), and visual impairment in a population-based study of older adults.
DESIGN: Cross-sectional study.
PARTICIPANTS: There were 1913 participants aged 63 to 102 years at the 20-year Beaver Dam Eye Study follow-up examination in 2008-2010, of whom 1540 (2980 eyes) had gradable spectral-domain optical coherence tomography (SD OCT) scans of the macula in at least 1 eye.
METHODS: The presence of ERMs and other retinal lesions was determined by standardized grading of macular SD OCT scans and photographs of 3 standard fields.
MAIN OUTCOME MEASURES: Epiretinal membranes, VMT, macular cysts, PVCs, LMHs, FTMHs, and visual impairment.
RESULTS: By using SD OCT, the prevalence of ERMs (34.1%), VMT (1.6%), macular cysts (5.6%), PVCs (20.0%), LMHs (3.6%), and FTMHs (0.4%) was estimated. The prevalence of macular cysts (P < 0.001), ERMs (P < 0.001), and VMT (P = 0.005) increased with age; the prevalence of PVCs (P = 0.05) decreased with age; and the prevalence of LMHs was not associated with age (P = 0.70). The prevalence of macular cysts, LMHs, and ERMs was higher in eyes with a history of cataract surgery. Macular cysts and ERMs were more common in eyes with retinal diseases, such as proliferative diabetic retinopathy, retinal vein occlusion, and retinal detachment, than in eyes without these conditions. Macular cysts, ERMs, and FTMHs were associated with visual impairment. While adjusting for age and sex, macular cysts (odds ratio [OR], 3.96; P < 0.0001), PVCs (OR, 1.45, P = 0.007), LMHs (OR, 10.62; P < 0.001), VMT (OR, 2.72, P = 0.01), and visual impairment (OR, 3.23; P < 0.001) were more frequent in eyes with ERMs compared with eyes without ERMs.
CONCLUSIONS: Epiretinal membranes are associated with macular cysts, PVCs, LMHs, VMT, and visual impairment. Further follow-up will allow better understanding of the natural history of ERMs and VMT and their relationships to the development of macular cysts and LMHs in the aging population.
Retinal thickness measured by spectral-domain optical coherence tomography in eyes without retinal abnormalities: the Beaver Dam Eye Study
Am J Ophthalmol. 2015 Mar;159(3):445-56.e1. doi: 10.1016/j.ajo.2014.11.025. Epub 2014 Nov 25.
PURPOSE: To examine relationships of age, sex, and systemic and ocular conditions with retinal thickness measured by spectral-domain ocular coherence tomography (SD OCT) in participants without retinal disease.
DESIGN: Longitudinal study.
METHODS: setting: Population-based cohort. study population: Persons aged 43-86 years living in Beaver Dam, Wisconsin in 1988-1990. observation procedures: Retinal thickness was measured via SD OCT at the Beaver Dam Eye Study examination in 2008-2010. Retinal disease was determined by ophthalmoscopy, fundus photography, or SD OCT. main outcome measures: Retinal thickness from the inner limiting membrane to the Bruch membrane.
RESULTS: The retina was thickest in the inner circle (mean 334.5 μm) and thinnest in the center subfield (285.4 μm). Mean retinal thickness decreased with age in the inner circle (P < .0001) and outer circle (P < .0001). Adjusting for age, eyes in men had thicker retinas than eyes in women in the center subfield (P < .001) and inner circle (P < .001). Sex, axial length/corneal curvature ratio, and peak expiratory flow rate were associated with center subfield thickness. Sex and peak expiratory flow rate were associated with retinal thickness in the inner circle. Alcohol consumption, age, axial length/corneal curvature ratio, cataract surgery, ocular perfusion pressure, and peak expiratory flow rate were associated with retinal thickness in the outer circle.
CONCLUSIONS: This study provides data for retinal thickness measures in eyes of individuals aged 63 years and older without retinal disease. This information may be useful for clinical trials involving the effects of interventions on retinal thickness and for comparisons with specific retinal diseases affecting the macula.
Development of a semi-automatic segmentation method for retinal OCT images tested in patients with diabetic macular edema
PLoS One. 2013 Dec 26;8(12):e82922. doi: 10.1371/journal.pone.0082922. eCollection 2013.
PURPOSE: To develop EdgeSelect, a semi-automatic method for the segmentation of retinal layers in spectral domain optical coherence tomography images, and to compare the segmentation results with a manual method.
METHODS: SD-OCT (Heidelberg Spectralis) scans of 28 eyes (24 patients with diabetic macular edema and 4 normal subjects) were imported into a customized MATLAB application, and were manually segmented by three graders at the layers corresponding to the inner limiting membrane (ILM), the inner segment/ellipsoid interface (ISe), the retinal/retinal pigment epithelium interface (RPE), and the Bruch's membrane (BM). The scans were then segmented independently by the same graders using EdgeSelect, a semi-automated method allowing the graders to guide/correct the layer segmentation interactively. The inter-grader reproducibility and agreement in locating the layer positions between the manual and EdgeSelect methods were assessed and compared using the Wilcoxon signed rank test.
RESULTS: The inter-grader reproducibility using the EdgeSelect method for retinal layers varied from 0.15 to 1.21 µm, smaller than those using the manual method (3.36-6.43 µm). The Wilcoxon test indicated the EdgeSelect method had significantly better reproducibility than the manual method. The agreement between the manual and EdgeSelect methods in locating retinal layers ranged from 0.08 to 1.32 µm. There were small differences between the two methods in locating the ILM (p = 0.012) and BM layers (p<0.001), but these were statistically indistinguishable in locating the ISe (p = 0.896) and RPE layers (p = 0.771).
CONCLUSIONS: The EdgeSelect method resulted in better reproducibility and good agreement with a manual method in a set of eyes of normal subjects and with retinal disease, suggesting that this approach is feasible for OCT image analysis in clinical trials.
Effect of optical coherence tomography scan decentration on macular center subfield thickness measurements
Invest Ophthalmol Vis Sci. 2013 Jul 2;54(7):4512-8. doi: 10.1167/iovs.13-12265.
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.
Signal quality assessment of retinal optical coherence tomography images
Invest Ophthalmol Vis Sci. 2012 Apr 24;53(4):2133-41. doi: 10.1167/iovs.11-8755.
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.