Matthew S. Muller

Non-mydriatic confocal retinal imaging using a digital light projector

A digital light projector is implemented as an integrated illumination source and scanning element in a confocal nonmydriatic retinal camera, the Digital Light Ophthalmoscope (DLO). To simulate scanning, a series of illumination lines are rapidly projected on the retina. The backscattered light is imaged onto a 2-dimensional rolling shutter CMOS sensor. By temporally and spatially overlapping the illumination lines with the rolling shutter, confocal imaging is achieved. This approach enables a low cost, flexible, and robust design with a small footprint. The 3rd generation DLO technical design is presented, using a DLP LightCrafter 4500 and USB3.0 CMOS sensor. Specific improvements over previous work include the use of yellow illumination, filtered from the broad green LED spectrum, to obtain strong blood absorption and high contrast images while reducing pupil constriction and patient discomfort.

Utility of hard exudates for the screening of macular edema.

Purpose The purpose of this study was to determine whether hard exudates (HEs) within one disc diameter of the foveola is an acceptable criterion for the referral of diabetic patients suspected of clinically significant macular edema (CSME) in a screening setting. Methods One hundred forty-three adults diagnosed as having diabetes mellitus were imaged using a nonmydriatic digital fundus camera at the Alameda County Medical Center in Oakland, CA. Nonstereo fundus images were graded independently for the presence of HE near the center of the macula by two graders according to the EyePACS grading protocol. The patients also received a dilated fundus examination on a separate visit. Clinically significant macular edema was determined during the dilated fundus examination using the criteria set forth by the Early Treatment Diabetic Retinopathy Study. Subsequently, the sensitivity and specificity of HEs within one disc diameter of the foveola in nonstereo digital images used as a surrogate for the detection of CSME diagnosed by live fundus examination were calculated. Results The mean (±SD) age of 103 patients included in the analysis was 56 ± 17 years. Clinically significant macular edema was diagnosed in 15.5% of eyes during the dilated examination. For the right eyes, the sensitivity of HEs within one disc diameter from the foveola as a surrogate for detecting CSME was 93.8% for each of the graders; the specificity values were 88.5 and 85.1%. For the left eyes, the sensitivity values were 93.8 and 75% for each of the two graders, respectively; the specificity was 87.4% for both graders. Conclusions This study supports the use of HE within a disc diameter of the center of the macula in nonstereo digital images for CSME detection in a screening setting.

Comparison of Cysts in Red and Green Images for Diabetic Macular Edema

ABSTRACT Purpose To investigate whether cysts in diabetic macular edema are better visualized in the red channel of color fundus camera images, as compared with the green channel, because color fundus camera screening methods that emphasize short-wavelength light may miss cysts in patients with dark fundi or changes to outer blood retinal barrier. Methods Fundus images for diabetic retinopathy photoscreening were acquired for a study with Aeon Imaging, EyePACS, University of California Berkeley, and Indiana University. There were 2047 underserved, adult diabetic patients, of whom over 90% self-identified as a racial/ethnic identify other than non-Hispanic white. Color fundus images at nominally 45 degrees were acquired with a Canon Cr-DGi non-mydriatic camera (Tokyo, Japan) then graded by an EyePACS certified grader. From the 148 patients graded to have clinically significant macular edema by the presence of hard exudates in the central 1500 μm of the fovea, we evaluated macular cysts in 13 patients with cystoid macular edema. Age ranged from 33 to 68 years. Color fundus images were split into red, green, and blue channels with custom Matlab software (Mathworks, Natick, MA). The diameter of a cyst or confluent cysts was quantified in the red-channel and green-channel images separately. Results Cyst identification gave complete agreement between red-channel images and the standard full-color images. This was not the case for green-channel images, which did not expose cysts visible with standard full-color images in five cases, who had dark fundi. Cysts appeared more numerous and covered a larger area in the red channel (733 ± 604 μm) than in the green channel (349 ± 433 μm, P < .006). Conclusions Cysts may be underdetected with the present fundus camera methods, particularly when short-wavelength light is emphasized or in patients with dark fundi. Longer wavelength techniques may improve the detection of cysts and provide more information concerning the early stages of diabetic macular edema or the outer blood retinal barrier.

3D microscopy for microfabrication quality control

A novel stereo microscope adapter, the SweptVue, has been developed to rapidly perform quantitative 3D microscopy for cost-effective microfabrication quality control. The SweptVue adapter uses the left and right stereo channels of an Olympus SZX7 stereo microscope for sample illumination and detection, respectively. By adjusting the temporal synchronization between the illumination lines projected from a Texas Instruments DLP LightCrafter and the rolling shutter on a Point Grey Flea3 CMOS camera, micrometer-scale depth features can be easily and rapidly measured at up to 5 μm resolution on a variety of microfabricated samples. In this study, the build performance of an industrial-grade Stratasys Object 300 Connex 3D printer was examined. Ten identical parts were 3D printed with a lateral and depth resolution of 42 μm and 30 μm, respectively, using both a rigid and flexible Stratasys PolyJet material. Surface elevation precision and accuracy was examined over multiple regions of interest on plateau and hemispherical surfaces. In general, the dimensions of the examined features were reproducible across the parts built using both materials. However, significant systemic lateral and height build errors were discovered, such as: decreased heights when approaching the edges of plateaus, inaccurate height steps, and poor tolerances on channel width. For 3D printed parts to be used in functional applications requiring micro-scale tolerances, they need to conform to specification. Despite appearing identical, our 3D printed parts were found to have a variety of defects that the SweptVue adapter quickly revealed.

Fixation Stability and Scotoma Mapping for Patients with Low Vision

Purpose To develop a simplified device that performs fundus perimetry techniques such as fixation mapping and kinetic perimetry. Methods We added visual stimulation to a near-infrared retinal imager, the laser scanning digital camera (LSDC). This device uses slit scanning illumination combined with a two-dimensional CMOS (complementary metal oxide semiconductor) detector, with continuous viewing of the retina. The CMOS readout was synchronized with the slit scanning, thereby serving as a confocal aperture to reduce stray light in retinal images. A series of retinal images of 36 degrees was automatically aligned to provide data for fixation maps and quantification of fixation stability. The LSDC and alignment techniques also provided fundus viewing with retinal location correction for scotoma mapping. Results First, fixation mapping was readily performed in patients with central scotoma or amblyopia. The automatic alignment algorithm allowed quantification of fixation stability in patients with macular pathologies that did not cause scotoma. Second, fixation stability was rapidly and quantitatively assessed by the automatic registration of the series of retina images. There was no significant difference in the fixation stability with automatic versus manual alignment. Kinetic perimetry demonstrated that fundus imaging helped reduce the variability of perimetric data by identifying and preventing false-positives caused by eye motion. We found that the size of the blind spot was significantly larger for dark targets on brighter backgrounds than when the contrast was reversed (p < 0.045). This is consistent with incremental targets being detected partially or wholly because of scattered light falling on more sensitive retinal locations. Conclusions Fundus perimetry with the LSDC allows for a wide range of fixation and perimetry tasks.

Multiply Scattered Light Imaging for Low Cost and Flexible Detection of Subretinal Pathology

A novel technique to easily and rapidly switch between direct and indirect-scattered imaging modes using a rolling electronic aperture is applied to inexpensively detect early signs of retinal layer degradation.

Inexpensive and Flexible Slit-Scanning Confocal Imaging Using a Rolling Electronic Aperture

The temporal synchronization between slit-scanning illumination and line-by-line CMOS detection permits the creation of a flexible electronic confocal aperture. A novel imaging system design is presented, highlighting the advantages and challenges to this technique.

Confocal retinal imaging using a digital light projector with a near infrared VCSEL source

A custom near infrared VCSEL source has been implemented in a confocal non-mydriatic retinal camera, the Digital Light Ophthalmoscope (DLO). The use of near infrared light improves patient comfort, avoids pupil constriction, penetrates the deeper retina, and does not mask visual stimuli. The DLO performs confocal imaging by synchronizing a sequence of lines displayed with a digital micromirror device to the rolling shutter exposure of a 2D CMOS camera. Real-time software adjustments enable multiply scattered light imaging, which rapidly and cost-effectively emphasizes drusen and other scattering disruptions in the deeper retina. A separate 5.1” LCD display provides customizable visible stimuli for vision experiments with simultaneous near infrared imaging.

Non-Mydriatic Confocal Retinal Imaging Using a Digital Light Projector

A digital light projector is implemented as an integrated illumination source and scanning element in a confocal nonmydriatic retinal camera, the DLP-Cam. To simulate scanning, a series of illumination lines are rapidly projected on the retina. The backscattered light is imaged onto a 2-dimensional rolling shutter CMOS sensor. By temporally and spatially overlapping the illumination lines with the rolling shutter, confocal imaging is achieved. This approach enables a low cost, flexible, and robust design with a small footprint. Qualitative image comparison with commercial non-mydriatic SLOs and fundus cameras shows comparable fine vessel visibility and contrast.

Polarimetric Imaging of the Human Retina for the Quantification of Neural and Blood Vessel Status

A Several key structures and molecules in the human retina are known to exhibit birefringence, and therefore can be probed with polarimetric imaging. By using scanned illumination, the contrast is increased, revealing otherwise undetectable pathology.