Optical Coherence Tomography
domain technology promises improved image resolution and added capabilities.
Figure 1. Spectral domain OCT mapping of retinal pigment epithelium
drusen. The thickness map clearly shows that the retina is thinner over the drusen.
According to Philip J. Rosenfeld, MD, PhD, new
optical coherence tomography (OCT) instruments, which will likely be commercially
available within the next year, will offer enhanced capabilities. At the 2006 Retinal
Physician Symposium (May 31-June 3, Atlantis, Paradise Island, Bahamas), he introduced
the Miami Macula Mapper, an enhanced version of the technology, which has been developed
by Carmen A. Puliafito, MD, MBA, Robert Knighton, PhD, Shuliang Jiao, PhD, and Giovanni
Gregori, PhD, of the Bascom Palmer Eye Institute's OCT Laboratory.
The Miami Macula Mapper uses a spectral domain detection technique,
rather than the time domain technique used by currently available OCT instruments.
"Spectral domain is next-generation OCT," Dr. Rosenfeld said.
Time domain OCT makes use of one detector, and each A-scan requires
the movement of several mechanical parts. Rather than a single detector, spectral
domain OCT uses a spectrometer with up to 2000 detector elements and has no moving
parts, which means information is collected much faster. Spectral domain OCT's imaging
speed is 29,000 A-scans per second compared with time domain OCT's 400 A-scans per
Faster acquisition speed produces more sensitive, higher-resolution
images, including 3-D images, which significantly improves visualization of retinal
structures. The Miami Macula Mapper is capable of 4-μm resolution. "You can
break up the scans into as few or as many as you want," Dr. Rosenfeld said. "There
is much more flexibility in the resolution that can be obtained." Furthermore, retinal
layers can be segmented and represented by 3-D thickness maps (Figure 1).
Spectral domain OCT can also generate a fundus image similar
to that acquired with a scanning laser ophthalmoscope, and the spatial location
of each OCT sectional image is registered on the OCT fundus image automatically
(Figure 2). "Spectral domain has point-to-point registration in reference to surface
landmarks," Dr. Rosenfeld explained. "It allows users to precisely place where the
pathology is in the different layers of the retina based on the vascular landmarks
of the fundus image."
The sophisticated algorithms used in spectral domain OCT permit
more elegant, clinically useful analyses, Dr. Rosenfeld said. He also clarified
that spectral domain OCT is known as "high-resolution," which is different from
"ultra high-resolution." The
2. Spectral domain OCT can generate a fundus image, and the spatial location of
each OCT sectional image is registered on the fundus image automatically.
ultra high resolution OCT technology, which is currently
being used as a research device at New England Eye Center in Boston and a site in
Vienna, will not be commercially available.
Figure 1. In this patient, one anti-VEGF treatment
reduced diffuse edema, but did not eliminate sub-RPE fluid. Two subsequent treatments
eliminated all subretinal, intraretinal and diffuse edema. Visual acuity improved
from 20/70 to 20/40.
OCT in Wet AMD
shed light on using OCT to track the efficacy of anti-VEGF therapies.
With the availability of anti-VEGF therapies
marking the beginning of a new era in the treatment of neovascular age-related
macular degeneration (AMD), the role of optical coherence tomography (OCT) becomes
even more vital. According to David M. Brown, MD, "As the PrONTO study has shown,
OCT is absolutely essential for assessing response to an anti-VEGF agent and for
determining when to retreat."
At the 2006 Retinal Physician Symposium (May 31-June 3, Atlantis,
Paradise Island, Bahamas), Dr. Brown emphasized the importance of using the qualitative
rather than the quantitative data provided by OCT. He cited a recently published
paper by Sadda, et al.1,which indicated that retinal thickness measurement
errors can and do occur frequently with the current Stratus OCT (Carl Zeiss Meditec)
segmentation and analysis algorithms in patients with neovascular AMD. Errors are
inherent, Dr. Brown explained, because scans for computing center-point thickness
require patient fixation, retinal boundaries need to be determined, and subretinal
pigment epithelium (sub-RPE) fluid is not taken into account. "In AMD, determining
retinal boundaries is difficult because of schisis channels and the different layers,"
he said. In addition, eccentric lesions can interfere with central subfield measurements.
After this patient received four anti-VEGF treatments, subretinal fluid, diffuse
edema, intraretinal cysts and sub-RPE fluid remained. A subsequent treatment with
a different anti-VEGF agent did not eliminate the intraretinal cysts. The patient
was treated again with the first agent, to avoid further elevation of intraocular
pressure, but fluid returned. Treatment with a third anti-VEGF agent led to the
desired anatomic response.
qualitative OCT, what you see is what you get," Dr. Brown said. Therefore, physicians
monitoring the effects of anti-VEGF treatments with OCT should examine each high-resolution
scan for signs of fluid reaccumulation, as was done in the PrONTO study. When fluid
returns, it does so in the form of diffuse edema, intraretinal cysts, subretinal
edema, or sub-RPE fluid, and it means the disease is "DISSing" disrespecting
the treatment, Dr. Brown said. "Qualitative OCT, 'DISS,' equals leakage,
which equals disease activity. If AMD is DISSing your treatment, treat more often
or change agents" (Figures 1 and 2).
As the 1-year results from the PIER and PrONTO studies showed,
no treatment or treatment schedule has the same effect in every patient, Dr. Brown
said. "There-fore it is essential to determine anatomic response to treatment with
qualitative OCT, tailor retreatment to patient response, and change agents when
Speaking with Retinal Physician after the symposium, Dr. Brown
said quantitative OCT values are useful for monitoring diffuse diabetic macular
edema, but he never uses them to guide treatment for AMD patients. After he uses
fluorescein angiography to make the initial diagnosis of neovascular AMD, he follows
patients with OCT.
"Just like a macula-off retinal detachment has to be anatomically
corrected before visual acuity can be maximized, I believe in AMD the best
visual acuity gains occur when the retina is entirely deturgesced," he said. "I
treat with anti-VEGF agents monthly until all signs of fluid are gone; no diffuse
edema, no intraretinal cysts, no subretinal fluid and no sub-RPE fluid. I then follow
patients with the retinal thickness map protocol on the OCT3 (six high-resolution
cuts 30° apart). I see them every 6 weeks and retreat at the first sign of
any recurrent leakage."
1. Sadda SR, Wu Z, Walsh AC, et al. Errors
in retinal thickness measurements obtained by optical coherence tomography. Ophthalmol.
Scale Scores Probability of AMD Progression
assessment provides practical approach to patient prognosis.
A simple scale to estimate the risk of AMD progression
based on the presence of large drusen and pigment abnormalities may improve early
detection of choroidal neovascularization (CNV), according to Susan B. Bressler,
MD, the Julia G. Levy, PhD professor of ophthalmology, Johns Hopkins University
School of Medicine, The Wilmer Eye Institute. Dr. Bressler spoke on behalf of the
AREDS Research Group at the May 2006 Retinal Physician Symposium.
The development of the in-depth AMD research severity scale by
the AREDS Research Group led to the formulation of the simplified AMD severity scale.1
The format of the simplified scale was suggested by three observations that were
recognized during the construct of the research scale:
1. A strong association between drusen area and largest drusen
2. A low frequency of retinal pigment epithelium depigmentation
and/or geographic atrophy in the absence of increased pigment
3. Bilateral large drusen is a stronger risk factor than unilateral
The simplified scale should enable clinicians to differentiate
AMD patients into risk profiles, making it practical to target those who are most
likely to benefit from preventive measures and more apt to progress as well as benefit
from intensive monitoring, Dr. Bressler said.
DRUSEN SIZE AND PIGMENTARY CHANGES
made the assumption that a clinician would be more likely to effectively assess
maximum drusen size in the posterior pole as compared to maximum area occupied by
drusen," Dr. Bressler said. "Fur-
thermore, we thought clinicians could [more
easily] sort patients by those who had large drusen and those who did not."
For the purposes of this scale, Dr. Bressler noted, large drusen
are defined as a drusen within two disc diameters of the foveal center, with a diameter
of at least 125 microns. "Conveniently, this is equal to the average width of a
retinal vein at the disc margin," Dr. Bressler said.
addition to drusen size, the AMD severity scale requires the clinician to assess
the presence or absence of definite pigmentary changes. "This may consist of either
focal increases in pigment or areas of depigmentation within one disc diameter of
the fovea or areas of non-central geographic atrophy within two disc diameters of
the fovea," Dr. Bressler said.
SCORING THE RISK
The severity scale provides a summary score
from 0 to 4 that differentiates a patient's risk of developing advanced AMD
over 5 years, from a low of <1% to as high as 50%. For example, an individual
without large drusen and without pigment abnormalities in both eyes would have zero
risk factors; whereas, an individual with large drusen and pigment abnormalities
in both eyes would have four risk factors.
The scores correspond to a marked differential in the risk of
developing advanced AMD in one or both eyes. Zero risk factors imply a negligible
risk for advanced AMD. One risk factor implies a small 5-year risk of 3%.
"There is at least a doubling of risk for each successive step
with two risk factors corresponding to a 12% risk; three risk factors corresponding
to a 25% risk; and four risk factors corresponding to a 50% risk," Dr. Bressler
said. "If you are examining a patient who has advanced AMD in one eye, and you want
to assess his or her risk of developing advanced AMD in the remaining eye, you would
score the eye with advanced AMD as a 2, and then continue on to the eye at risk
and assess it for large drusen and pigment changes," Dr. Bressler said. "If the
eye at risk has neither, then the patient's total score is 2, with roughly a 12%
5-year rate of progression in the fellow eye. Whereas if the fellow eye has large
drusen and pigment changes, then the fellow eye is at the high risk rate of 50%."
An individual who does not have large drusen in either eye, but
has bilateral extensive intermediate size drusen, would be assigned a score of one-half
for each eye, or a total of 1 for the patient. If neither eye has a pigment change,
then the total patient score is 1, which implies a 3% risk that one or both eyes
will develop advanced AMD within 5 years.
GOAL: CLINICAL UTILITY
"Our objective was to develop a scale that
could be useful in the clinic, and we hope this has been accomplished by concentrating
on these two characteristics that can be assessed on routine ophthalmoscopy or review
of fundus photographs," Dr. Bressler said. "With this scale, you may be able to
determine who you want to follow more often to potentially improve the early detection
1. AREDS Report #18: Arch Ophthalmol. 2005;123:1570-1574.
Retinal Physician, Issue: September 2006