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ISSN 0972-0200
Recent Advances
Adaptive Optics
Apoorva Ayachit , Ruchi Goel , Guruprasad Ayachit2, Smriti Nagpal1, Ashwin Mohan3, Rohit Shetty3, Divya Kishore1
Guru Nanak Eye Centre, New Delhi1
M M Joshi Eye Institute, Hubli, Karnataka, India2
Narayana Nethralaya Bangalore, Karnataka, India3
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have three main elements: a mechanism for wavefront
correction, typically a deformable mirror; a wavefront
sensor (usually Hartmann Shack type) and a command and
control algorithm (software) to integrate the two4 (Figure 1).
A deformable mirror is capable of changing shapes through
the use of actuators that push and pull on the mirror. In the
case of the Imagine Eyes system, there are 52 actuators that
push and pull on an 8 × 8 array, while the system developed
by Wavefront Sciences (Advanced Medical Optics, AMO,
Santa Ana, California) has 800 centroids.5
In simple words, the deformable mirror by virtue of its
shape changing abilities “cleans up” the aberrations sensed
by the wavefront sensor and produces a sharp image despite
any defocus.
Abstract
Physicists and ophthalmologists, since time immemorial have
aggressively tried to break new ground in trying to get a good look at
the retina and its myriad pathologies. Although fundus photography,
optical coherence tomography and fundus fluorescein angiography
have largely been very successful in imaging the retina and give a clear
understanding of pathology affecting it, researchers are continuously
looking for newer tools to assess the retinal structure at a cellular
level. Adaptive optics with its ability to overcome optical aberrations
has been able to achieve this non- invasively. Its advantages, clinical
applications and shortcomings are under scrutiny and only time will
reveal its utility in a clinical setting.
Keywords: retinal imaging, adaptive optics
The retina is a unique end organ that can be non- invasively
visualized to understand the effects of ocular or systemic
diseases. Fundus camera, Optical Coherence Tomography
(OCT) and Scanning Laser Ophthalmoscopy (SLO)
have made it possible to observe the effect of disease on
neural elements, microvasculature and photoreceptors at
microscopic levels.1,2 But these modalities are limited by
various aberrations that interfere with imaging at a cellular
level. Adaptive optics (AO) has stormed into the arena of
retinal imaging and by its ability to circumvent both lower
and higher order aberrations, AO has made it possible to
image individual cells in the retina.3
In 1953, Horace Babcock first proposed the use of a
deformable optical element, along with a wave front sensor,
to compensate for atmospheric distortions in telescopic
imaging. The principle of adaptive optics has been utilized
in astronomical telescopes, laser communication systems,
microscopy and optical fabrication. The first adaptive optics
fundus camera was developed at the University of Rochester
about 20 years ago.4
Figure 1: Principle of Adaptive Optics
Physics and its Application
Light from the retina is received by the aberrometer which
then is sensed by a deformable mirror. A corrected wavefront
is thus received as a high resolution retinal image.
AO by itself does not produce an image and it must be
integrated with an existing imaging device like a fundus
camera, SLO or Spectral Domain- OCT (although flood
light illumination can be used). All adaptive optics systems
Adaptive optics (AO) Retinal Imaging Systems
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AO fundus camera: This system has been used mainly
for studying the cone mosaic, cone directionality and
reflectance. (Figure 2) Apart from photoreceptors; Retinal
Pigment Epithelium, White Blood Cells in the vessels,
retinal vessel wall and lamina cribrosa can be visualized.
Considerable image processing effort is needed including
registration, montaging and quantitative analysis. Despite
these setbacks, AO fundus imaging has been a major
breakthrough in terms of the resolution achieved.6
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DOI
http://dx.doi.org/10.7869/djo.135
Del J Ophthalmol - Vol 26 No: 1 July-September 2015
46
E-ISSN 2454-2784
Recent Advances
Figure 2: AO image showing cone mosaic
Adaptive optics scanning laser ophthalmoscopy (AO-SLO)
- AO integrated with an SLO produces highly magnified,
high resolution images. A wide field line scanning laser
ophthalmoscope is used which creates an image by detection
of a flying spot raster focused on the retina in a confocal
arrangement. The confocality aids in better lateral resolution.
Eye tracking softwares correct for micro-movements of the
eyes and enable imaging even in non- mydriatic states.7
Adaptive optics Optical coherence tomography (AO-OCT) The peculiarity in OCT is that the axial and lateral resolution
is decoupled. Axial resolution is limited by the coherence
properties of light. Lateral resolution is limited by focal spot
size, significantly degraded by the eye’s aberrations. Thus
AO can be used to compensate for the eye’s monochromatic
aberrations. AO is capable of resolving individual
photoreceptors in 3 dimensions. 3D visualization of nerve
fibre layer, lamina cribrosa, ganglion cells, as well as RPE
photoreceptor mosaic and choriocapillaris is possible using
high speed scans using AO- OCT (1,20,000 scans/ second) 6
Clinical Applications
Zhang et al studied the inter and intra- individual variability
of cones in the macula in young adults. AOSLO was used
in 40 eyes of 20 subjects ranging from 19-29 years. Cone
density was assessed on a sampling grid of 2.4 mm X2.4 mm
in the central macula. In their study they found that peak
density is 168890±21348 cones/ mm2 (mean± SD) in right eye
and 167434±26068 cones/ mm2 in the left eye. Both right and
left eyes exhibited sharp density gradients. At 150 micron
eccentricity, the cone density was 55% of the peak and at
1.2mm, it was 10% of the peak. They noted that the AO
findings correlated well with the histology findings.8
The AURA study by Dabir et al studied the cone packing
density in emmetropic patients. Cone packing densities
were calculated at 2 degrees and 3 degrees from the fovea in
the temporal, superior, nasal and inferior quadrants. Mean
cone packing densities were highest temporally, followed
by superior, nasal and inferior. Mean cone packing densities
at 2 degree from the fovea was 25154.67±4777.69 and at 3
degrees was 21.366.28±4167.86. Micro-perimetry revealed
that the sensitivity of cones were highest at the fovea and
decreased as the distance from the fovea increased. Thus
they concluded that the sensitivity correlated with cone
packing density.9 Retinal dystrophies- Wolfing et al studied
the cone directionality, sensitivity and density in patients
of atrophic Bull’s eye lesions. A 6 degree montage was
obtained with the AOSLO. They demonstrated larger cones
at 1.25 degrees from the fovea and decreased cone density.
There was also a 5.5- fold reduction in amplitude evidenced
by multi- focal ERG. This report showed that the density
and functionality have a correlation and the larger cones
indicated that the cones may not be normally functioning.
At the foveal centre the patient’s cone density was 31,100
cones/ sq mm (normal average- 199,200 cones/ sq mm).10
Studies suggest that diabetic retinopathy could be now
considered a neurovascular disorder rather than a
microvasculopathy. There has been growing evidence of
photoreceptor apoptosis and neural degeneration which in
turn lead to vascular drop out.11 Lombardo et al11 studied
the para foveal cone density in a series of 11 patients
diagnosed with type 1 diabetes and studied its correlation
with the duration of diabetes, glycosylated hemoglobin
level, the presence of retinopathy and the SD-OCT retinal
thickness. These parameters were studied in patients of
no retinopathy or mild non proliferative retinopathy. The
study revealed statistically significant differences in cone
densities between diabetics and control healthy subjects (p
<0.001). At 230, 350 and 460 microns, the average density in
the study group was 91%, 90% and 89% of the average cone
density in the control group, respectively. Thus there was a
subtle decline in the photoreceptor density and this study
revealed structural alterations at the cellular level much
before clinical DR manifested.12
CSCR (Central serous chorioretinopathy) - Ooto and
collaeagues used AOSLO to examine CSCR eyes with
resolved subretinal fluid. Resolved CSCR have fewer cones
per square mm than control subjects. They demonstrated
this in patients with 20/20 or better visual acuity as well as
in those with a preserved Inner Segment/Outer Segment
(IS/OS) junction as seen on SD-OCT. Those patients with
gaps in IS/OS junctions had further decline in the number
of photoreceptors. Thus they demonstrated the subclinical
loss of photoreceptors even after a single episode of CSCR,
in patients who recovered excellent visual acuity.13
Macular holes- Ooto and Hangai used AOSLO to study
surgically closed macular holes and their correlation with
pre- operative symptom duration and visual acuity. After
standard 23 gauge 3- port vitrectomy, they observed
large dark areas of photoreceptor loss, the sizes of which
correlated with duration of pre- operative visual symptoms.
The photoreceptor density was lower even in eyes with
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maintained IS- OS junctions. Lower cone density correlated
with poorer post- operative visual acuity. The dark areas
corresponded to lower foveal sensitivities and thinner inner
and outer segments. Darker areas on AO were larger in eyes
with pre- operative cuff of fluid. AOSLO was thus valuable
even in eyes with good anatomical closure seen on SD-OCT.
This study gives insight into the possible pathogenesis of
macular holes, which they suggest is formed by avulsion of
focal neural tissue by antero- posterior traction.14 Epiretinal
membranes- the structural abnormalities underlying
vision changes are not known in ERMs. Only ILM folds
larger than 50 microns are detectable on SDOCT or colour
fundus photographs. AOSLO has revealed microfolds 520 microns in size. A study has shown the correlation of
metamorphopsia with these microfolds. Thus, AOSLO in
patients of metamorphopisa with a normal looking fundus
or a normal SDOCT may be able to provide evidence of
structural abnormalities in the photoreceptor layer.15
The pathophysiologic significance of paravascular
opacification seen by AO may be either cellular infiltration
or parietal thickening. AO imaging may even identify
subclinical retinal vasculitis, which is not detected by
ophthalmoscopy or Fundus Fluorescein Angiography. This
may contribute to the diagnosis and workup of a variety
of general inflammatory diseases. AO imaging may also
contribute to a better understanding of the process leading
to vascular occlusion, thereby helping to identify patients
at risk of severe visual loss. Therefore, AO imaging may
be a useful tool for the detection, early diagnosis, and
management of retinal vasculitis.16 Normal blood vessels
are depicted in (Figure 3). Lamina Cribrosa- The number
of pores in the lamina cribrosa has been seen to be larger
and of better quality in AOSLO imaging than conventional
Figure 4: AO image showing pores in the lamina cribrosa
colour photography (Figure 4).
Pore area has also been studied and found to be larger
in glaucomatous eyes. Thus, AOSLO is a useful imaging
technology for assessing laminar pore number and area.
The laminar pore area may be affected by axial length and
IOP.17
Conclusion
Thus we see that AO has far-reaching clinical applications.
However, the lengthy analyses and algorithms for image
acquisition, montaging and processing and patient
fixation problems are some established drawbacks of AO
technology. Moreover, the cost makes it prohibitive for
a clinical office setting. In spite of this, recent years have
seen an explosion of data on the various applications of
AO in clinical research and experimental ophthalmology.
The quantitative measurement of cone density based
on eccentricity from the fovea, its correlation with cone
functionality based on micro-perimetry and its accurate
agreement with histopathology, all the while being a
non- invasive technique, makes it a formidable tool in the
armamentarium of a clinical researcher. It can be used to
test newer treatments and surgical methods and can be used
for long term longitudinal monitoring.18
Cite This Article as: Ayachit A, Goel R, Ayachit G, Nagpal S, Mohan A,
Shetty R, Kishore D. Adaptive Optics. Delhi J Ophthalmol. 2015;26:46-9.
Acknowledgements: None
Date of Submission: 27.05.2015
Conflict of interest: None declared
Figure 3: AO image showing blood vessels
Del J Ophthalmol - Vol 26 No: 1 July-September 2015
48
Date of Acceptance: 14.06.15
E-ISSN 2454-2784
Recent Advances
References
1.
Kagemann L, Ishikawa H, Wollstein G, Gabriele M, Schuman
JS. Visualization of 3-D high speed ultrahigh resolution optical
coherence tomographic data identifies structures visible in 2D
frames. Opt Express 2009; 17:4208-20.
2. Rudnicka AR, Burk RO, Edgar DF, Fitzke FW. Magnification
characteristics of fundus imaging systems. Ophthalmology
1998; 105:2186-92.
3. Kozak I. Retinal imaging using adaptive optics technology.
Saudi J Ophthalmol 2014; 28:117-22.
4. Robert Tyson. Principles of Adaptive Optics. 3rd ed. Florida:
CRC Press, Taylor and Francis Group; 2011.
5. Battu R, Dabir S, Khanna A, Kumar AK, Roy AS. Adaptive
optics imaging of the retina. Indian J Ophthalmol 2014; 62:60-5.
6. Godara P, Dubis AM, Roorda A, Duncan JL, Carroll J. Adaptive
optics retinal imaging: emerging clinical applications. Optom
Vis Sci 2010; 87:930-41.
7. Hammer DX, Ferguson RD, Bigelow CE, Iftimia NV, Ustun
TE, Burns SA. Adaptive optics scanning laser ophthalmoscope
for stabilized retinal imaging. Opt Express 2006; 14:3354–67.
8. Zhang T, Godara P, Blanco ER, Griffin RL, Wang X, Curcio
CA, et al. Variability in Human Cone Topography Assessed
by Adaptive Optics Scanning Laser Ophthalmoscopy. Am J
Ophthalmol 2015 Apr 30. [Epub ahead of print]
9. Dabir S, Mangalesh S, Kumar KA, Kummelil MK, Sinha
RA, Shetty R. Variations in the cone packing density with
eccentricity in emmetropes. Eye 2014; 28:1488-93.
10. Wolfing JI, Chung M, Carroll J, Roorda A, Williams DR.
High-resolution retinal imaging of cone-rod dystrophy.
Ophthalmology 2006; 113:1019.e1.
11. Lombardo M, Parravano M, Serrao S, Ducoli P, Stirpe M,
Lombardo G. Analysis of retinal capillaries in patients with
type 1 diabetes and nonproliferative diabetic retinopathy
using adaptive optics imaging. Retina 2013; 33:1630-9.
12. Lombardo M, Parravano M, Lombardo G, Varano M,
Boccassini B, Stirpe M, et al. Adaptive optics imaging of
parafoveal cones in type 1 diabetes. Retina 2014; 34:546-57.
13. Ooto S, Hangai M, Sakamoto A, Tsujikawa A, Yamashiro K,
Ojima Y, et al. High-resolution imaging of resolved central
serous chorioretinopathy using adaptive optics scanning laser
ophthalmoscopy. Ophthalmology 2010; 117:1800-9, 1809.e1.
14. Ooto S, Hangai M, Takayama K, Ueda-Arakawa N, Hanebuchi
M, Yoshimura N. Photoreceptor damage and foveal sensitivity
in surgically closed macular holes: an adaptive optics scanning
laser ophthalmoscopy study. Am J Ophthalmol 2012 ; 154:174186.e2.
15. Ooto S, Hangai M, Takayama K, Sakamoto A, Tsujikawa A,
Oshima S, et al. High-resolution imaging of the photoreceptor
layer in epiretinal membrane using adaptive optics scanning
laser ophthalmoscopy. Ophthalmology 2011; 118:873-81.
16. Errera MH, Coisy S, Fardeau C, Sahel JA, Kallel S, Westcott
M, et al. Retinal vasculitis imaging by adaptive optics.
Ophthalmology 2014; 121:1311-2.e2.
17. Akagi T, Hangai M, Takayama K, Nonaka A, Ooto S, Yoshimura
N. In vivo imaging of lamina cribrosa pores by adaptive optics
scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci 2012;
53:4111-9.
18. Kim JE, Chung M. Adaptive optics for retinal imaging: current
status. Retina 2013; 33:1483-6.
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Corresponding author:
Apoorva Ayachit MS
Guru Nanak Eye Centre, Maulana Azad Medical College,
Maharaja Ranjit Singh Marg,New Delhi, India
Email: [email protected]