Center for the Prevention and Treatment of Visual Loss

Iowa City, IA, United States

Center for the Prevention and Treatment of Visual Loss

Iowa City, IA, United States
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Garvin M.K.,Center for the Prevention and Treatment of Visual Loss | Abramoff M.D.,Center for the Prevention and Treatment of Visual Loss | Abramoff M.D.,University of Iowa | Kwon Y.H.,Ophthalmology and Visual science
Investigative Ophthalmology and Visual Science | Year: 2012

PURPOSE. To correlate the thicknesses of focal regions of the macular ganglion cell layer with those of the peripapillary nerve fiber layer using spectral-domain optical coherence tomography (SD-OCT) in glaucoma subjects. METHODS. Macula and optic nerve head SD-OCT volumes were obtained in 57 eyes of 57 subjects with open-angle glaucoma or glaucoma suspicion. Using a custom automated computer algorithm, the thickness of 66 macular ganglion cell layer regions and the thickness of 12 peripapillary nerve fiber layer regions were measured from registered SD-OCT volumes. The mean thickness of each ganglion cell layer region was correlated to the mean thickness of each peripapillary nerve fiber layer region across subjects. Each ganglion cell layer region was labeled with the peripapillary nerve fiber layer region with the highest correlation using a color-coded map. RESULTS. The resulting color-coded correlation map closely resembled the nerve fiber bundle (NFB) pattern of retinal ganglion cells. The mean r 2 value across all local macularperipapillary correlations was 0.49 (± 0.11). When separately analyzing the 30 glaucoma subjects from the 27 glaucomasuspect subjects, the mean r 2 value across all local macularperipapillary correlations was significantly larger in the glaucoma group (0.56 ± 0.13 vs. 0.37 ± 0.11; P ± 0.001). CONCLUSIONS. A two-dimensional (2-D) spatial NFB map of the retina can be developed using structure-structure relationships from SD-OCT. Such SD-OCT-based NFB maps may enhance glaucoma detection and contribute to monitoring change in the future. © 2012 The Association for Research in Vision and Ophthalmology, Inc.


Wang J.-K.,University of Iowa | Kardon R.H.,University of Iowa | Kardon R.H.,Center for the Prevention and Treatment of Visual Loss | Kupersmith M.J.,Roosevelt Hospital and New York Eye and Ear Infirmary | And 2 more authors.
Investigative Ophthalmology and Visual Science | Year: 2012

PURPOSE. To develop an automated method for the quantification of volumetric optic disc swelling in papilledema subjects using spectral-domain optical coherence tomography (SDOCT) and to determine the extent that such volumetric measurements correlate with Friśen scale grades (from fundus photographs) and two-dimensional (2-D) peripapillary retinal nerve fiber layer (RNFL) and total retinal (TR) thickness measurements from SD-OCT. METHODS. A custom image-analysis algorithm was developed to obtain peripapillary circular RNFL thickness, TR thickness, and TR volume measurements from SD-OCT volumes of subjects with papilledema. In addition, peripapillary RNFL thickness measures from the commercially available Zeiss SD-OCT machine were obtained. Expert Friśen scale grades were independently obtained from corresponding fundus photographs. RESULTS. In 71 SD-OCT scans, the mean (6 standard deviation) resulting TR volumes for Friśen scale 0 to scale 4 were 11.36 ± 0.56, 12.53 ± 1.21, 14.42 ± 2.11, 17.48 ± 2.63, and 21.81 ± 3.16 mm3, respectively. The Spearman's rank correlation coefficient was 0.737. Using 55 eyes with valid Zeiss RNFL measurements, Pearson's correlation coefficient (r) between the TR volume and the custom algorithm's TR thickness, the custom algorithm's RNFL thickness, and Zeiss' RNFL thickness was 0.980, 0.929, and 0.946, respectively. Between Zeiss' RNFL and the custom algorithm's RNFL, and the study's TR thickness, r was 0.901 and 0.961, respectively. CONCLUSIONS. Volumetric measurements of the degree of disc swelling in subjects with papilledema can be obtained from SDOCT volumes, with the mean volume appearing to be roughly linearly related to the Friśen scale grade. Using such an approach can provide a more continuous, objective, and robust means for assessing the degree of disc swelling compared with presently available approaches. © 2012 The Association for Research in Vision and Ophthalmology, Inc.


Mohan K.,Center for the Prevention and Treatment of Visual Loss | Mohan K.,Iowa State University | Kecova H.,Iowa State University | Hernandez-Merino E.,Iowa State University | And 3 more authors.
Investigative Ophthalmology and Visual Science | Year: 2013

PURPOSE. To evaluate retina and optic nerve damage following experimental blast injury. METHODS. Healthy adult mice were exposed to an overpressure blast wave using a custombuilt blast chamber. The effects of blast exposure on retina and optic nerve function and structure were evaluated using the pattern electroretinogram (pERG), spectral domain optical coherence tomography (OCT), and the chromatic pupil light reflex. RESULTS. Assessment of the pupil response to light demonstrated decreased maximum pupil constriction diameter in blast-injured mice using red light or blue light stimuli 24 hours after injury compared with baseline in the eye exposed to direct blast injury. A decrease in the pupil light reflex was not observed chronically following blast exposure. We observed a biphasic pERG decrease with the acute injury recovering by 24 hours postblast and the chronic injury appearing at 4 months postblast injury. Furthermore, at 3 months following injury, a significant decrease in the retinal nerve fiber layer was observed using OCT compared with controls. Histologic analysis of the retina and optic nerve revealed punctate regions of reduced cellularity in the ganglion cell layer and damage to optic nerves. Additionally, a significant upregulation of proteins associated with oxidative stress was observed acutely following blast exposure compared with control mice. CONCLUSIONS. Our study demonstrates that decrements in retinal ganglion cell responses can be detected after blast injury using noninvasive functional and structural tests. These objective responses may serve as surrogate tests for higher CNS functions following traumatic brain injury that are difficult to quantify. © 2013 The Association for Research in Vision and Ophthalmology, Inc.


John S.W.M.,Howard Hughes Medical Institute | John S.W.M.,The Jackson Laboratory | John S.W.M.,Tufts University | Harder J.M.,The Jackson Laboratory | And 3 more authors.
Journal of Glaucoma | Year: 2014

At present, no animal models fully embody exfoliation syndrome or exfoliation glaucoma. Both genetic and environmental factors appear critical for disease manifestation, and both must be considered when generating animal models. Because mice provide a powerful mammalian platform for modeling complex disease, this paper focuses on mouse models of exfoliation syndrome and exfoliation glaucoma. Copyright © 2014 by Lippincott Williams & Wilkins.


Kawasaki A.,University of Lausanne | Kawasaki A.,Umeå University | Crippa S.V.,University of Lausanne | Kardon R.,University of Iowa | And 3 more authors.
Investigative Ophthalmology and Visual Science | Year: 2012

Purpose. We characterized the pupil responses that reflect rod, cone, and melanopsin function in a genetically homogeneous cohort of patients with autosomal dominant retinitis pigmentosa (adRP). Methods. Nine patients with Gly56Arg mutation of the NR2E3 gene and 12 control subjects were studied. Pupil and subjective visual responses to red and blue light flashes over a 7 log-unit range of intensities were recorded under dark and light adaptation. The pupil responses were plotted against stimulus intensity to obtain red-light and blue-light response curves. Results. In the dark-adapted blue-light stimulus condition, patients showed significantly higher threshold intensities for visual perception and for a pupil response compared to controls (P = 0.02 and P = 0.006, respectively). The rod-dependent, blue-light pupil responses decreased with disease progression. In contrast, the cone-dependent pupil responses (light-adapted red-light stimulus condition) did not differ between patients and controls. The difference in the retinal sensitivity to blue and red stimuli was the most sensitive parameter to detect photoreceptor dysfunction. Unexpectedly, the melanopsin-mediated pupil response was decreased in patients (P = 0.02). Conclusions. Pupil responses of patients with NR2E3-associated adRP demonstrated reduced retinal sensitivity to dim blue light under dark adaptation, presumably reflecting decreased rod function. Rod-dependent pupil responses were quantifiable in all patients, including those with non-recordable scotopic electroretinogram, and correlated with the extent of clinical disease. Thus, the chromatic pupil light reflex can be used to monitor photoreceptor degeneration over a larger range of disease progression compared to standard electrophysiology. © 2012 The Association for Research in Vision and Ophthalmology, Inc.


Joshi V.S.,University of Iowa | Reinhardt J.M.,University of Iowa | Garvin M.K.,University of Iowa | Garvin M.K.,Center for the Prevention and Treatment of Visual Loss | And 2 more authors.
PLoS ONE | Year: 2014

The separation of the retinal vessel network into distinct arterial and venous vessel trees is of high interest. We propose an automated method for identification and separation of retinal vessel trees in a retinal color image by converting a vessel segmentation image into a vessel segment map and identifying the individual vessel trees by graph search. Orientation, width, and intensity of each vessel segment are utilized to find the optimal graph of vessel segments. The separated vessel trees are labeled as primary vessel or branches. We utilize the separated vessel trees for arterial-venous (AV) classification, based on the color properties of the vessels in each tree graph. We applied our approach to a dataset of 50 fundus images from 50 subjects. The proposed method resulted in an accuracy of 91.44% correctly classified vessel pixels as either artery or vein. The accuracy of correctly classified major vessel segments was 96.42%. © 2014 Joshi et al.


Hu Z.,University of Iowa | Hu Z.,Doheny Eye Institute | Niemeijer M.,University of Iowa | Abramoff M.D.,University of Iowa | And 3 more authors.
IEEE Transactions on Medical Imaging | Year: 2012

Segmenting retinal vessels in optic nerve head (ONH) centered spectral-domain optical coherence tomography (SD-OCT) volumes is particularly challenging due to the projected neural canal opening (NCO) and relatively low visibility in the ONH center. Color fundus photographs provide a relatively high vessel contrast in the region inside the NCO, but have not been previously used to aid the SD-OCT vessel segmentation process. Thus, in this paper, we present two approaches for the segmentation of retinal vessels in SD-OCT volumes that each take advantage of complimentary information from fundus photographs. In the first approach (referred to as the registered-fundus vessel segmentation approach), vessels are first segmented on the fundus photograph directly (using a k-NN pixel classifier) and this vessel segmentation result is mapped to the SD-OCT volume through the registration of the fundus photograph to the SD-OCT volume. In the second approach (referred to as the multimodal vessel segmentation approach), after fundus-to-SD-OCT registration, vessels are simultaneously segmented with a k-NN classifier using features from both modalities. Three-dimensional structural information from the intraretinal layers and neural canal opening obtained through graph-theoretic segmentation approaches of the SD-OCT volume are used in combination with Gaussian filter banks and Gabor wavelets to generate the features. The approach is trained on 15 and tested on 19 randomly chosen independent image pairs of SD-OCT volumes and fundus images from 34 subjects with glaucoma. Based on a receiver operating characteristic (ROC) curve analysis, the present registered-fundus and multimodal vessel segmentation approaches [area under the curve (AUC) of 0.85 and 0.89, respectively] both perform significantly better than the two previous OCT-based approaches (AUC of 0.78 and 0.83, p < 0.05). The multimodal approach overall performs significantly better than the other three approaches (p < 0.05). © 1982-2012 IEEE.


Song Q.,University of Iowa | Song Q.,General Electric | Bai J.,University of Iowa | Garvin M.K.,University of Iowa | And 4 more authors.
IEEE Transactions on Medical Imaging | Year: 2013

Segmentation of multiple surfaces in medical images is a challenging problem, further complicated by the frequent presence of weak boundary evidence, large object deformations, and mutual influence between adjacent objects. This paper reports a novel approach to multi-object segmentation that incorporates both shape and context prior knowledge in a 3-D graph-theoretic framework to help overcome the stated challenges. We employ an arc-based graph representation to incorporate a wide spectrum of prior information through pair-wise energy terms. In particular, a shape-prior term is used to penalize local shape changes and a context-prior term is used to penalize local surface-distance changes from a model of the expected shape and surface distances, respectively. The globally optimal solution for multiple surfaces is obtained by computing a maximum flow in a low-order polynomial time. The proposed method was validated on intraretinal layer segmentation of optical coherence tomography images and demonstrated statistically significant improvement of segmentation accuracy compared to our earlier graph-search method that was not utilizing shape and context priors. The mean unsigned surface positioning errors obtained by the conventional graph-search approach 6.30 ± 1.58 μm) was improved to 5.14±0.99 μ m when employing our new method with shape and context priors. © 2012 IEEE.


Koehn D.R.,University of Iowa | Meyer K.J.,University of Iowa | Anderson M.G.,University of Iowa | Anderson M.G.,Center for the Prevention and Treatment of Visual Loss
Investigative Ophthalmology and Visual Science | Year: 2015

PURPOSE. Central corneal thickness (CCT) is a quantitative trait associated with keratoconus and primary open-angle glaucoma. Although CCT is highly heritable, known genetic variations explain only a fraction of the phenotypic variability. The purpose of this study was to identify additional CCT-influencing loci using inbred strains of mice. METHODS. Cohorts of 82 backcrossed (N2) and 99 intercrossed (F2) mice were generated from crosses between recombinant inbred BXD24/TyJ and wild-derived CAST/EiJ mice. Using anterior chamber optical coherence tomography, mice were phenotyped at 10 to 12 weeks of age, genotyped based on 96 genome-wide single nucleotide polymorphisms (SNPs), and subjected to quantitative trait locus (QTL) analysis. RESULTS. In an analysis of total CCT among all mice, two loci passed the significance threshold of P = 0.05. These were on Chr 3 and Chr 11 (Cctq4 and Cctq5, respectively). A third locus of interest was identified in a two-dimensional pairwise analysis; this locus on Chr 14 (Cctq6) exhibited a significant additive effect with Cctq5. Independent analyses of the dataset for epithelial and stromal thickness revealed that Cctq4 is specific to the epithelial layer and that Cctq5 and Cctq6 are specific to the stromal layer. CONCLUSIONS. Our findings demonstrate a quantitative multigenic pattern of CCT inheritance in mice and identify three previously unrecognized CCT-influencing loci: Cctq4, Cctq5, and Cctq6. This is the first demonstration that distinct layers of the cornea are under differential genetic control and highlights the need to refine the design of future genome-wide association studies of CCT. © 2015 The Association for Research in Vision and Ophthalmology, Inc.


Garvin M.K.,Center for the Prevention and Treatment of Visual Loss
Investigative ophthalmology & visual science | Year: 2013

To compare the reproducibility of spectral-domain optical coherence tomography (SD-OCT)-based ganglion cell-layer-plus-inner plexiform-layer (GCL+IPL) thickness measurements for glaucoma patients obtained using both a publicly available and a commercially available algorithm. Macula SD-OCT volumes (200 × 200 × 1024 voxels, 6 × 6 × 2 mm(3)) were obtained prospectively from both eyes of patients with open-angle glaucoma or with suspected glaucoma on two separate visits within 4 months. The combined GCL+IPL thickness was computed for each SD-OCT volume within an elliptical annulus centered at the fovea, based on two algorithms: (1) a previously published graph-theoretical layer segmentation approach developed at the University of Iowa, and (2) a ganglion cell analysis module of version 6 of Cirrus software. The mean overall thickness of the elliptical annulus was computed as was the thickness within six sectors. For statistical analyses, eyes with an SD-OCT volume with low signal strength (<6), image acquisition errors, or errors in performing the commercial GCL+IPL analysis in at least one of the repeated acquisitions were excluded. Using 104 eyes (from 56 patients) with repeated measurements, we found the intraclass correlation coefficient for the overall elliptical annular GCL+IPL thickness to be 0.98 (95% confidence interval [CI]: 0.97-0.99) with the Iowa algorithm and 0.95 (95% CI: 0.93-0.97) with the Cirrus algorithm; the intervisit SDs were 1.55 μm (Iowa) and 2.45 μm (Cirrus); and the coefficients of variation were 2.2% (Iowa) and 3.5% (Cirrus), P < 0.0001. SD-OCT-based GCL+IPL thickness measurements in patients with early glaucoma are highly reproducible.

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