Download ARVO 2015 Annual Meeting Abstracts 533 Adaptive optics and

ARVO 2015 Annual Meeting Abstracts
533 Adaptive optics and retinal imaging
Thursday, May 07, 2015 12:00 PM–1:45 PM
702/704/706 Paper Session
Program #/Board # Range: 5883–5889
Organizing Section: Visual Psychophysics / Physiological Optics
Program Number: 5883
Presentation Time: 12:00 PM–12:15 PM
Imaging the retinal pigment epithelium mosaic with AO-OCT
Zhuolin Liu, Omer P. Kocaoglu, Tim L. Turner, Donald T. Miller.
School of Optometry, Indiana university, Bloomington, IN.
Purpose: The retinal pigment epithelium (RPE) is critical for support
and maintenance of photoreceptors. While dysfunction of the RPE
underlies numerous retinal pathologies, biomarkers sensitive to
early changes in RPE have been elusive. Because such changes
start at cellular level, there has been increased interest in targeting
the spatial arrangement and distribution of individual RPE cells. To
do so in the living human retina is extremely challenging, owing
to the lack of intrinsic contrast of RPE, optical waveguiding by the
overlying photoreceptors, and blurring by ocular aberrations. In this
study, we take advantage of the micron-level 3D resolution afforded
by adaptive optics and optical coherence tomography (AO-OCT)
to overcome these obstacles in order to visualize RPE cells and
investigate their packing geometry.
Methods: Using the Indiana AO-OCT imaging system (λc=790 nm,
Δλ=42 nm), volumes of 1°×1° field of view were acquired at 3° and
10° temporal retina in two normal subjects. Volumes were registered,
segmented, and RPE en face images extracted. Voronoi analysis was
applied to the en face images to determine number of neighbors (NN)
and center-to-center nearest neighbor distance (NND) of the RPE
cells. 2D power spectra were used to provide additional information
about cell spacing.
Results: RPE cell mosaics were resolved in both subjects and retinal
eccentricities. Voronoi analysis indicates hexagonal cells (with six
NN) are most frequent (>50%) at 3° retinal eccentricity and are
of lower frequency (<50%) at 10° retinal eccentricity. NND was
11.4±2.2 μm and 12.8±3.0 μm for subject 1 at 3° and 10° retinal
eccentricities respectively, and 12.0±2.0 μm for subject 2 at 3°.
Processing of 10° data for subject 2 is ongoing. NND measurements
are consistent with the 2D power spectra estimations of 11.9 μm and
12.9 μm of subject 1 (3° and 10°), and 12.7 μm of subject 2 (3°).
Conclusions: AO-OCT imaging permits visualization and
quantification of the RPE packing geometry in the living human
retina.
Commercial Relationships: Zhuolin Liu, None; Omer P.
Kocaoglu, None; Tim L. Turner, None; Donald T. Miller, U.S.
Patent 7,364,296 (P)
Support: NEI grants 1R01 EY018339 and P30 EY019008.
Program Number: 5884
Presentation Time: 12:15 PM–12:30 PM
Photoreceptor topography and marked discontinuity at the optic
nerve head in young healthy subjects
Ann E. Elsner, Joel A. Papay, Christopher A. Clark, Lucie Sawides,
Alberto De Castro, Stephen A. Burns. Optometry, Indiana University,
Bloomington, IN.
Purpose: Individual differences in photoreceptor topography include
a higher density of cones in the fovea and different rates of decrease
of cone density with increasing eccentricity. We investigated the lack
of a smooth change in cone density at the border of and extending
into the scleral crescent, where there are no apparent retinal pigment
epithelial (RPE) cells.
Methods: To measure cone density at the optic nerve head
without the presence of confounding factors such as high myopia
or glaucoma, we recruited two subjects < 35 yr with wide scleral
crescents despite healthy eyes and low refractive errors. The
topography of the scleral crescent was documented with SD-OCT
(Spectralis). The hyperreflectivity indicating the lack of melanincontaining RPE cells and the scleral pattern of birefringence were
localized with scanning laser polarimetry (GDx). For high resolution
imaging at the scleral crescent, a focus series with the Indiana
Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) was
used to document the thinned aspect of the scleral crescent and
topography change, along with depigmentation. We used the AOSLO
to image photoreceptors, the scleral crescent, and the overlying
retinal blood vessels. The AOSLO had two channels for imaging
photoreceptors via direct backscatter and multiple scattering, using
center wavelengths of 785 and 810 nm. We documented cones in the
scleral crescent with two operators. Two masked graders counted
cones in 6 sampled regions per image, computing cone density with
visual angle.
Results: Cones density changed markedly near the scleral crescent
over RPE cells and within the scleral crescent, where there was no
evidence of RPE cells. Patches of higher cone density were found
near the scleral crescent, but also regions of low density and even
cones that appeared sideways in or near the scleral crescent. The ratio
of cone density on and near the edge of scleral crescent to farther
away and having RPE cells varied from 0.50 to 1.4 within a single
image. In contrast, cones sampled within a single image but nearer to
the fovea had more uniform coverage, ranging in density by only .83
to .99.
Conclusions: Cone density, known to decrease systematically with
increasing distance from the fovea, increases in some patches near
the optic nerve head. Cones that are not over RPE cells have irregular
densities and sometimes orientations.
Commercial Relationships: Ann E. Elsner, None; Joel A. Papay,
None; Christopher A. Clark, None; Lucie Sawides, None; Alberto
De Castro, None; Stephen A. Burns, None
Support: NIH Grants EY007624, EY004395, and P30EY019008
Program Number: 5885
Presentation Time: 12:30 PM–12:45 PM
Variability in human cone topography enabled by adaptive optics
scanning laser ophthalmoscopy (AOSLO) imaging of foveal
centers
Tianjiao Zhang2, 1, Christine A. Curcio1, Yuhua Zhang1, 2.
1
Ophthalmology, The University of Alabama at Birmingham,
Birmingham, AL; 2Biomedical Engineering, The University of
Alabama at Birmingham, Birmingham, AL.
Purpose: Accurate assessment of variability of the human cone
topography is important for interpreting the effects of aging and
disease on the photoreceptor mosaic. We measure foveal cone
densities to acquire a better estimation of variability between eyes of
single individuals and between individuals, using a new generation
research AOSLO.
Methods: Forty eyes of 20 subjects with normal retinal health aged
19-29 years were studied. The refractive errors of the participants
range from -3.0 D to 0.63 D and the fellow eye refractive error
difference of individual subject is less than 0.50 D. AOSLO was
performed to image the cone photoreceptors. Cone density was
assessed on a two-dimensional mesh grid over the central 2.4 mm x
2.4 mm macula at up to 139 points. Mean cone densities, standard
deviation, the coefficient of variation (CV), and cumulative cone
numbers as a function of eccentricity were calculated to estimate
the inter-subject variability. Cone density difference between fellow
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
eyes was statistically assessed with a mixed model approach and
quantified by the root-mean-square (RMS) and the maximum
difference.
Results: The peak densities of all eyes are 168,162 ± 23,529 cones/
mm2 (mean ± SD) (CV = 0.14). The mean cone density agrees well
with the histological data (p = 0.9983 for both eyes). The total
number of cones within the cone-dominated foveola is 38,311 ±
2,319 (mean ± SD) (CV = 0.06). The RMS cone density difference
between fellow eyes is 6.78%, and the maximum intra-subject
difference is 23.6%. There is no difference in the association between
eccentricity and cone density in fellow eyes for the superior/nasal
(p=0.8503), superior/temporal (p=0.1551), inferior/nasal (p=0.8609),
and inferior/temporal (p=0.6662) quadrants of the retina.
Conclusions: By measuring the foveal center cone density in a
large number of eyes, we were able to determine the center of many
retinae, thereby accurately assessing the cone density variability.
Our results agree well with data provided by classical histology. We
have confirmed that in living human eyes, though cone densities vary
significantly in the fovea, the total number of cones within the conedominated foveola is less variant both within and between subjects.
Thus, the total number of foveola cones may serve as an important
measure for assessing cone loss due to aging or disease.
Cone density and total cone counts.
Commercial Relationships: Tianjiao Zhang, None; Christine A.
Curcio, None; Yuhua Zhang, None
Support: This project is funded by EyeSight Foundation of
Alabama (YZ), International Retina Research Foundation (YZ),
5R21EY021903 (YZ), and R01EY06109 (CC) and institutional
support from Research to Prevent Blindness, EyeSight Foundation of
Alabama, Buck Trust of Alabama, and NIH P30 EY003039.
Program Number: 5886
Presentation Time: 12:45 PM–1:00 PM
Structural properties of the cone photoreceptor packing: Cone
spacing and local anisotropy assessed with a cone-averaging
method
Lucie Sawides, Alberto De Castro, Stephen A. Burns. School of
Optometry, Indiana University, Bloomington, IN.
Purpose: To rapidly estimate cone spacing properties of the normal
cone photoreceptor mosaic and to measure local anisotropies in the
hexagonal pattern using a cone-averaging method.
Methods: The Indiana high-resolution Adaptive Optics Scanning
Laser Ophthalmoscope was used to image the cone photoreceptors of
5 normal healthy subjects (refractive error: -2.25±1.35 D, 28.8 ± 3.4
years old, 0.5% tropicamide dilated pupil).
Measurement of cones were recorded while the subjects looked
at each corner and the center of a 1 degree imaging field (0.5 Airy
disk confocal aperture). In addition four strips of 2x5 degrees of
cones corresponding to the four primary meridians (Temporal (T),
Nasal (N), Superior (S), Inferior (I)) were recorded using a 2degrees
imaging field (and 1.5 Airy disk confocal aperture).
Montages of average images were generated using an automated
algorithm (combining Matlab, i2k Retina and Adobe Photoshop).
Cone spacing properties were analyzed using a custom program that
automatically identified individual cones, within a window (50 or
100 microns) that varied with retinal location. Within each window,
interior subregions around each cone were extracted and averaged,
providing a “kernel” image of an average cone and its surrounding
retina. From each kernel image, we measured the averaged cone
spacing –computed as the first maximum of the radial profile, then
estimated the orientation and spacing anisotropy of the hexagonal
patterns based in determining the principle axes of the packing
(fig.1).
Results: There was a lower averaged cone spacing (higher cone
density) along the horizontal (T, N) meridians than along the vertical
(S, I) meridians. Locally the cone spacing was lower in vertical
than in horizontal axes for all meridians near the fovea (<1°) with
horizontal/vertical ratio of: 1.08±0.04 (T), 1.04±0.05 (N), 1.03±0.03
(S) and 1.05±0.01 (I). This tendency was maintained for Temporal
and Nasal meridians in the parafovea (up to 5°) while it reversed
for Superior meridian (1.11±0.07 (T), 1.10±0.06 (N), 0.97±0.05 (S),
1.00±0.03 (I)).
Conclusions: The method allows rapid automated estimates of cone
packing properties and provides an analysis of individual difference
in cone spacing and local anisotropies of the hexagonal cone array.
fig1: Kernel images with axes of the hexagonal packing (one subject,
Temporal and Superior meridians from 0.1° to 4° eccentricity)
Commercial Relationships: Lucie Sawides, None; Alberto De
Castro, None; Stephen A. Burns, None
Support: NIH EY04395; P30EY019008
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
Program Number: 5887
Presentation Time: 1:00 PM–1:15 PM
Magnification Characteristics on Optical Coherence Tomography
Systems
Dirk-Uwe G. Bartsch. Ophthalmology-Shiley Eye Ctr, Univ of
California-San Diego, La Jolla, CA.
Purpose: Recent advances in optical coherence tomography (OCT)
technology have led to the expansion of this technology into all areas
of medicine. A large number of clinical studies have been conducted
in areas such as glaucoma, macular degeneration, Alzheimer’s
disease, and others. In these studies patients with different refractive
errors are studied with different OCT devices using a variety of
imaging protocols that measure retinal thickness. Our purpose was
to study the lateral and axial magnification characteristics in six
different optical coherence tomography devices in a model eye and
draw conclusions for clinical studies.
Methods: We build an eye model with a simulated retina and
an achromatic doublet lens. The axial length of the eye model
was adjustable to yield a corresponding defocus of +4D to -10D
from emmetropia. We imaged the model eye with six different
optical coherence tomographs (CirrusOCT, Optos OCT, Optovue,
SpectralisOCT, StratusOCT, and Topcon DRI). We measured the
lateral dimension of features on the simulated retina with each
instrument. Additionally, we measured the axial dimension of a
microscope cover glass.
Results: In the first study we analyzed lateral magnification. The
SpectralisOCT was the only telecentric imaging system and showed
no magnification error with axial length. The Topcon DRI and
Optovue showed 12% and 13% variability over the defocus range,
respectively. The CirrusOCT and StratusOCT showed 30% variability
and the Optos OCT showed 45% variability over the defocus range.
In the second study we analyzed axial magnification error. None of
the instruments showed any axial magnification error.
Conclusions: Optical coherence tomography has dramatically
altered retinal imaging and anatomical understanding. Recently,
the instruments have been used to collect cross-sectional normative
databases in large number of patients. These studies rely on the
accuracy of the instrument for different refractive powers and
different axial lengths. It appears that several instruments exhibit
lateral magnification errors that need to be considered in crosssectional studies. Our studies indicate that none of the instruments
exhibit axial magnification error.
Commercial Relationships: Dirk-Uwe G. Bartsch, Heidelberg
Engineering (R), Heidelberg Engineering (R)
Support: NIH grant R01EY016323, NIH grant R01EY016323, NIH
grant 1P30EY022589, Research to Prevent Blindness
Program Number: 5888
Presentation Time: 1:15 PM–1:30 PM
Adaptive optics SLO/OCT for visualizing retinal vasculature
Michael Pircher, Franz Felberer, Matthias Rechenmacher, Richard
Haindl, Bernhard Baumann, Christoph K. Hitzenberger. Center for
Med Pyhs & Biomed Eng, Medical University of Vienna, Vienna,
Austria.
Purpose: To investigate the capability of our previously developed
adaptive optics scanning laser ophthalmoscope / optical coherence
tomography (AO-SLO/OCT) instrument for visualizing retinal
vasculature on a cellular level.
Methods: The SLO/OCT instrument records both imaging modalities
simultaneously and is operated at frame rates between 10 and 40 fps.
The field of view of the system can be varied between 1° x 1° and
4°x4°. The small field of view allows for an optimum adaptive optics
correction and high resolution imaging. The larger field of view is
used to generate overview images of the retina that enable an easy
determination of the imaged location. A typical measurement takes
several seconds. The en-face OCT technique provides two different
operating modes. In the first mode, a 3D volume scan of the retina is
recorded. Since the system is equipped with a dynamic focus scheme,
an entirely sharp 3D volume can be recorded. In the second mode,
the coherence plane and the focus plane can be set into a layer of
interest (such as a layer containing a vessel) and several en-face OCT
images of this layer are recorded with high speed. This enables the
visualization of dynamic processes such as blood flow and frame
averaging (similar to AO-SLO instruments) in order to increase
the signal to noise ratio. Axial eye motion is compensated using
active axial eye tracking and transverse motion is corrected in a post
processing step.
Results: Retinal blood flow on a cellular level was visualized
using this technology. For larger vessels the coherence gate was
set at different locations (anterior vessel wall, center part of vessel,
posterior vessel wall) within the tissue enabling the visualization of
different structures. The en-face OCT images show subtle details
such as individual erythrocytes or vessel walls. Frame averaging
enabled the visualization of different blood streams within a vessel.
In addition new structures within the surrounding tissue of the vessels
were found.
Conclusions: The AO-SLO/OCT instrument is well suited to study
dynamic processes such as blood flow on a cellular level. The high
depth resolution provided by OCT enables a clear separation between
different structures of the retina. The overview images and the 3D
information that can be recorded by the same instrument allow an
exact localization of the imaged region.
Commercial Relationships: Michael Pircher, None; Franz
Felberer, None; Matthias Rechenmacher, None; Richard Haindl,
None; Bernhard Baumann, None; Christoph K. Hitzenberger,
None
Support: Austrian Science Fund P22329-N02
Program Number: 5889
Presentation Time: 1:30 PM–1:45 PM
Structural and Functional Correlation of Retinal Photoreceptors
Overlying Lesions in White Dot Syndrome
Aniruddha Agarwal1, Mohamed K. Soliman1, 2, Nithya Rajagopalan1,
Mostafa S. Hanout1, Mohammad A. Sadiq1, Loren S. Jack1,
Salman Sarwar1, Diana V. Do1, Quan Nguyen1, Yasir J. Sepah1.
1
Ophthalmology, University of Nebraska Medical Center, Omaha,
NE; 2Ophthalmology, Assiut University, Assiut, Egypt.
Purpose: Lesions in white dot syndromes (WDS) may be associated
with photoreceptor (PR) loss. A prospective cohort study was
performed to evaluate PR density and correlate it with retinal
sensitivity overlying lesions in WDS.
Methods: Lesions of WDS (≤ 3 chosen/eye), within 5° foveal
eccentricity, were imaged using adaptive optics (AO) (rxt1, Imagine
Eyes, France), spectral-domain optical coherence tomography (SDOCT) and fundus autofluorescence (FAF) (Heidelberg Spectralis®,
Germany). In this study, lesions were defined as active if there were
presence of hyper-autofluorescence within the lesions. Eyes with
choroidal neovascularization, high myopia (> 6 diopters), media
opacity and other concomitant diseases were excluded. PR density
was calculated using manufacturer-provided AO Detect 1.0 software
after adjustment for axial length using IOLMaster® (Zeiss Meditech,
CA). Retinal sensitivity was assessed using microperimetry (MP)
(Optos SLO, UK) and correlated with PR density using Spearman
Rank Correlation test.
Results: Twenty-six lesions (9 patients: 7 females, mean age of
54.9 ± 16.6 years; 16 eyes) were analyzed. Diagnoses included
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
serpiginous choroiditis (2 eyes), birdshot choroidopathy (3 eyes),
presumed ocular histoplasmosis syndrome (2 eyes), punctate inner
choroidopathy (6 eyes) and multifocal choroiditis (4 eyes). Mean
PR density overlying 8 active lesions was 3076 ± 4654.89 cones/
mm2 and 6943.5 ± 5739.51 cones/mm2 overlying 18 inactive lesions
(p = 0.117). Mean PR density over 20 lesions with disrupted inner
segment-outer segment (IS-OS) junction on SD-OCT was 5005.64 ±
5024.89 cones/mm2 and 6943.5 ± 5739.51 cones/mm2 over 6 lesions
with intact IS-OS junction (p = 0.28). Mean retinal sensitivity (7.42 ±
4.70 dB) showed fair correlation with PR density (ρ = 0.43, p = 0.04).
Mean retinal sensitivity over lesions with intact IS-OS junction was
13 ± 2.45 dB and 5.71 ± 4.16 dB over lesions with disrupted IS-OS
junction (p = 0.007). Appearance of lesions on AO imaging is shown
in figure.
Conclusions: AO imaging may allow high-resolution analysis of
PR loss among lesions in WDS. Such microstructural changes may
correlate with functional loss.
Image shows an active lesion on FAF (A) associated with focal
hypo-intensities on AO imaging (yellow asterisks) suggestive of PR
loss (B). Healed lesions (C) show circumferential hypo-intense halo
(white arrowheads) surrounding area of scarring (D).
Commercial Relationships: Aniruddha Agarwal, None; Mohamed
K. Soliman, None; Nithya Rajagopalan, None; Mostafa S. Hanout,
None; Mohammad A. Sadiq, None; Loren S. Jack, None; Salman
Sarwar, None; Diana V. Do, None; Quan Nguyen, None; Yasir J.
Sepah, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].