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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. Source


Kawasaki A.,University of Lausanne | Kawasaki A.,Umea 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. Source


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. Source


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. Source


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. Source

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