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In Vivo AOSLO Imaging of Retinal Detachment Associated Pathology
Edward Randerson, Alfredo Dubra , PhD & Joseph Carroll , PhD
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Departments of Ophthalmology, Biophysics, and Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin
[email protected]
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Cone Inner Segments Within Dark Areas in Mac Hole
Disruption of the area of contact between the retina and the nourishing retinal pigment epithelium
(RPE) threatens the stability of our vision and its recovery following intervention. In vivo
interpretation of disruption is dependent on imaging techniques whose resolution is severely
restricted by inherent ocular aberrations. Adaptive Optics (AO), a newer imaging technique, is
capable of optically correcting these aberrations and allows in vivo imaging of the photoreceptor
mosaic at a resolution comparable to those available with histology.1
In retinal detachment associated pathology, disruptions of the Ellipsoid Zone (EZ) and Interdigitation
Zone (IZ) bands are visible on Optical Coherence Tomography (OCT) images. As these bands
originate from the rod and cone photoreceptors, their disruption has been correlated with severe
defects in visual acuity.2,3 In this study we sought to use AO imaging in combination with standard
clinical imaging to assess photoreceptor structure in patients with visual disturbances caused by
photoreceptor separation from the RPE.
Photoreceptor Imaging
EZ and IZ band disruptions in
OCT images appear as large
Light
Detector on-axis view
Detector 3
Cone Pedicle
“dark areas” in confocal AOSLO
Mirror
I −I
images. The confocal AOSLO
Annular
Inner process
2 1 3
silver
I +I
mirror
modality relies on waveguided
light from the photoreceptor that
Lens
Split-detector
Soma
Detector 2
has passed through both the
Lens
AOSLO
outer and inner segment of the
Inner segment
Detector 1
cell; these dark areas could
Outer Segment
indicate disrupted waveguiding
Eye
or more severe photoreceptor
degeneration.
A
recently
Confocal
developed split-detector AOSLO
modality allows visualization of
the photoreceptor inner segment in a manner independent of the cell’s waveguiding properties.4
This allows for a potentially more sensitive assessment of photoreceptor structure in and around
clinically detectable lesions.
Fundus
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3
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3
Confocal AOSLO
Clinical Imaging Techniques
Fundus images are useful for seeing gross
structure, OCT for visualizing the layers of
the retina, and AOSLO for evaluating the
integrity of the photoreceptor mosaic. As
lesions can sometimes be visible in
AOSLO images,5 but not OCT, clinical
imaging tools are unable to accurately
predict changes in Best-Corrected Visual
Acuity (BCVA).
Split-Detector AOSLO Shows Photoreceptor Structure in Dark Areas
Confocal AOSLO has been used to demonstrate residual cone structure within dark areas (as defined on OCT) in patients with Macular Hole (Mac Hole).2
Similar dark areas are present in en face OCT and confocal images from patients with vitreomacular traction (VMT), retinal detachment (RD), and central
serous retinopathy (CSR). Using the split-detector AOSLO imaging, we observed remnant inner segment structure within these lesions. Scale bars =
200 µm.
68 y.o.
Female
Mac Hole
Confocal AOSLO
Split-Detector AOSLO
63 y.o.
Male
RD
Split-Detector AOSLO
Split-Detector
Confocal / Split-Detector Merge
En face OCT
En face OCT
64 y.o.
Female
VMT
Confocal AOSLO
In previous studies of Mac Hole, dark areas were thought to be areas of
complete photoreceptor loss.7 Split-detector images of Mac Hole have
shown presence of cone inner segments, which may account for
patients that have a higher BCVA than projected based on the lesion
area. The color merge image demonstrates added information (blue)
that split-detector shows with respect to confocal (orange). Scale bars
= 50 µm.
Confocal AOSLO
Split-Detector AOSLO
En face OCT
69 y.o.
Female
CSR
Confocal AOSLO
Split-Detector AOSLO
En face OCT
Peripheral Rod Cells Visible in CSR Dark Areas
Microfolds Visible in Split-Detector Images
Waxy Membrane Found in Post-Operative RD
As part of the normal aging process, vitreous shrinks from the retina
towards the anterior eye. Anomalous VMT occurs when this retraction
adheres to the retina. In the untreated eye, severe disruption is visible
on OCT resulting in microfolds that interfere with visualization of cone
structure on AOSLO. In the treated eye, despite apparent resolution on
OCT, we see residual lesions in the AOSLO image (possibly accounting
for their 20/50 vision in that eye). Scale bars = 100 µm.
This waxy reflectivity was found on the surface of the Nerve Fiber Layer
(NFL) just nasal to the fovea. Other small membranes were found in
various peripheral locations. Waxy membranes are thought to contain a
connective tissue component and are often visualized on OCT, though
this membrane was not visible on en face imaging. These small
remnants post-operatively could account for a waxy membrane that
predisposed the patient to RD.6 Scale bars = 50 µm.
OS, untreated
OD, treated
Confocal
CSR results from choroidal fluid infiltrating the subretinal space.8 This
condition is distinct from vitreoschisis in that the fluid detachment
comes from the outer spaces of the eye rather than the inner. When
viewed with confocal imaging, cone signals are irregular and
reflectance is distorted suggesting the presence of some
non-waveguiding photoreceptors. Split-detector images show not only
the presence of intact cones, but also intact rods within the area of
detachment. This suggests some cones have degenerated, allowing the
remaining rods to swell. Scale bars = 25 µm.
Split-Detector
Confocal / Split-Detector Merge
Split-Detector
OCT
En Face OCT
En face OCT is currently used to visualize and measure
lesion size within the band of EZ disruption and for
localization of AOSLO images. An en face image is
made by plotting a contour along the EZ band in each
of 400 B-scans. Scans are then stacked to form a
projection of the specified segmentation. The resulting
image looks similar to a fundus photo, however, it
shows layers deep within the retina.
En face projection of EZ segmentation
AOSLO provides valuable information when studying retinal detachment associated pathology not accessible with existing clinical tools. Both
confocal and split-detector modalities provide useful information about the etiology and cellular structures associated with disease. Continued
imaging of patients with retinal detachment associated pathologies will help to identify unknown structures associated with various disease
presentations observed with AOSLO.
The unique presentation and recovery of patients with Mac Hole provides a unique opportunity to study photoreceptor morphology during the
retinal healing process. A longitudinal study of residual cone structure present in dark areas with split-detector imaging may be able to detect
changes in cone density and morphology. These changes may provide improved sensitivity, compared to OCT, in predicting recovery of visual
function following surgical intervention.
1. Carroll, J. et al. Adaptive Optics Retinal Imaging - Clinical Opportunities and Challenges. Informa Healthcare. Curr Eye Res.
38(7): 709-721, (2013).
2. Hansen, S. et al. Assessing Photoreceptor Structure Following Macular Hole Closure. Retin Cases Brief Rep. (in press).
3. Flatter, J. et al. Outer Retinal Structure After Closed-Globe Blunt Ocular Trauma. Retina. (2014).
4. Scoles, D. et al. In Vivo Imaging of Human Cone Photoreceptor Inner Segments. Invest Ophthalmol Vis Sci. 55(7): 4244-4251,
(2014).
5. Yokota, S. et al. Objective Assessment of Foveal Cone Loss Ratio in Surgically Closed Macular Holes Using Adaptive Optics
Scanning Laser Ophthalmoscopy. PLoS One. 8(5): e63786, (2013).
6. Scoles, D. et al. Microscopic Inner Retinal Hyper-Reflective Phenotypes in Retinal and Neurologic Disease. Invest
Ophthalmol Vis Sci. 55(7): 4015-4029, (2014).
7. Ooto, S. et al. Photoreceptor Damage and Foveal Sensitivity in Surgically Closed Macular Holes: An Adaptive Optics
Scanning Laser Ophthalmoscopy Study. Am J Opthalmol. 154(1): 174-186, (2012).
8. Ooto, S. et al. High-Resolution Imaging of Resolved Central Serous Chorioretinopathy Using Adaptive Optics Scanning
Laser Ophthalmoscopy. Ophthalmology. 117(9): 1800-1809, (2010).
The authors acknowledge the work and help of B. Higgins, P.
Summerfelt, M. Goldberg, C. Skumatz, C. Langlo, R. Cooper, J. Kim, T.
Connor, W. Wirostko, and K. Stepien.