Download Retinal fixation point location in the foveal avascular zone.

Investigative Ophthalmology & Visual Science, Vol. 31, No. 10, October 1990
Copyright © Association for Research in Vision and Ophthalmology
Retinal Fixation Point Location in the
Foveal Avascular Zone
Bernard 5. Zeffren,* Raymond A. Applegare,* Arthur Bradley,f and W. A. J. van Heuven"
The site of normal fixation is often assumed to be centered in the foveal avascular zone (FAZ). This
assumed anatomic relationship is used during photocoagulation therapy as an objective guide to avoid
damaging critical retinal structures on or near fixation. With laser therapy being directed closer and
closer to the center of the FAZ, the accuracy with which the center of the FAZ locates the retinal point
of fixation becomes an important therapeutic issue. Using an optimized technique for visualizing the
retinal vasculature entoptically, the authors determined the location of the retinal point of fixation with
respect to the foveal area vasculature in 26 eyes of 14 healthy subjects. In 23 eyes (12 subjects), a
traditional FAZ was observed, the other three eyes (two subjects) had capillaries near or crossing the
center of fixation. Of the 23 eyes with a traditional FAZ, 20 had centers of fixation located eccentric to
the center but in the FAZ, (average deviation from the center of the FAZ, 66.5 ± 49.5 /xm) with the
direction of deviation from the FAZ center appearing random. Consequently, when following protocols
that advocate photocoagulation treatment with spot centers closer to the FAZ center than 300 nm, the
center of the FAZ is a poor locator of a subject's retinal point of fixation. When using the FAZ as a
reference, the resulting uncertainty in the location of the subject's retinal point offixationincreases the
probability of significant damage to the actual point of fixation by up to 20%. Invest Ophthalmol Vis
Sci 31:2099-2105, 1990
The posterior pole of the eye contains the anatomic
fovea and foveola. These structures are highly specialized to maximize visual acuity. In the center of the
anatomic fovea, the inner retinal layers down to the
outer nuclear layer are displaced, forming a pit, the
foveola, which contains the highest density of cones
in the retina (147,000 cones per mm2).1 The retinal
capillaries in the area of the fovea typically form concentrically arranged channels ending in a capillary
loop approximately 0.5 mm across which outlines a
capillary-free zone known as the "foveal avascular
zone" (FAZ).1 The lateral displacement of inner retinal structures, including the retinal vasculature, presumably exists to leave an unobstructed light path to
the site of phototransduction, thereby enhancing
image quality.2
From the *Department of Ophthalmology, University of Texas
Health Science Center at San Antonio, San Antonio, Texas, and
the fDepartment of Visual Science, School of Optometry, Indiana
University, Bloomington, Indiana.
Supported by NIH grant EYO8OO5 to RAA, NIH grant EY07863
to AB, and an unrestricted research grant to the Department of
Ophthalmology, University of Texas Health Science Center at San
Antonio from the Research to Prevent Blindness, Inc. New York.
Arthur Bradley is also supported by the Indiana Institute for the
Study of Human Capabilities grant AFOSA #870089.
Reprint requests: Raymond A. Applegate, OD, PhD, Department of Ophthalmology, University of Texas Health Science
Center at San Antonio, San Antonio, TX 78284-7779.
In a normal observer, visual performance is maximized at the subject's point of fixation. That is, when
asked to fixate a point in space, normal observers
move their eyes such that the point of interest is
imaged on the retinal region providing the highest
resolution.3-4 The connection between fixation and
optimal resolution, together with the histologic specialization of the retina, suggests that a normal individual will move the eye to place the image of the
fixation point on the foveola. Thus the retinal point
of fixation and the foveola are assumed to be coincident and reasonably centered in the FAZ.
Given current therapeutic trends to photocoagulate closer and closer to the point of fixation using the
center of the FAZ as a guiding landmark,5"9 the accuracy with which the center of the FAZ locates the
point of fixation becomes critical. That is, when using
the FAZ as an anatomic landmark for locating the
retinal point of fixation, significant deviation of the
point of fixation from the center of the FAZ could
lead to placement of laser burns closer to, or further
from, the fovea than anticipated. As a result, burns
may unintentionally lead to inappropriate laser-induced damage or incomplete coverage or nontreatment of a (sub)retinal neovascular lesion due to its
assumed (as opposed to known) proximity to the retinal point of fixation.
We used optimization techniques for visualizing10
the smallest foveal capillaries entoptically to deter-
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INVESTIGATIVE OPHTHALMOLOGY 6 VISUAL SCIENCE / Ocrober 1990
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mine whether or not the retinal point used for fixation actually lies in the center of the FAZ, and if not,
whether or not the deviations are significant enough
to warrant clinical consideration.
Materials and Methods
A number of techniques have been used to examine the FAZ and its component capillaries in living
humans, including fluorescein angiography,""14 and
two noninvasive subjective psychophysical techniques: the "blue-field entoptic effect"1516 and the
entoptic visualization of the retinal vasculature
(commonly known as the Purkinje image)." 1718 The
blue-field entoptic effect provides the viewer an
image of the white corpuscles as they flow through
the retinal capillaries. The capillaries remain unseen,
and the actual form of the vascular tree must be constructed in the mind of the viewer. An optimized
Purkinje image allows simultaneous evaluation of a
persistent, easily visible, high-contrast image of the
foveal capillaries and the point of fixation.10
Instrumentation
Stimulus optimization for the entoptic visualization of the macular area retinal vasculature and FAZ
was achieved by modifying a standard Maxwellianview system.19 We call the system, schematically illustrated in Figure 1, the Vascular Entoptoscope.
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Source S, a 1-mm pinhole, back-illuminated by
light from a fiber optic passing through a blue filter
(3M, Visual Products Division, 3 M Center, St. Paul,
MN, color filter part #47 with peak transmittance at
470 nm), was set to rotate at a speed of 3.5 hertz in a
circular path 2 mm from, and concentric with, the
optical axis of the instrument. Light from S was first
collimated by lens L, and then imaged into the plane
of the subject's pupil with unit magnification by lens,
L2. An iris diaphragm (aperture A), imaged at optical
infinity by L2, served as the field stop for the eye-apparatus system.
A second channel provided the subject a view of
two dim point sources (PSi and PS2) optically conjugate with aperture A through a beam splitter, Bi.
Point source, PS,, was attached to a motorized X-Y
positioning plate and served as a guidelight for marking positions of interest in the field of view. Point
source, PS2, served as a stationary fixation point centered on the optical axis of the apparatus. The subject
controlled the position of PSi with a joystick and
could thereby locate, with respect to the point of fixation, any point on the capillary loop defining the
FAZ. A variable voltage signal reflecting the location
of moveable point source, PSl5 was sent from the X-Y
position plate to an X-Y plotter for hard-copy documentation of the border of the FAZ.
Alignment of the subject's pupil to the optical axis
of the apparatus and stabilization of the subject's
Monitor
Subject
X-Y
Joystick
X-Y Plotter
A toB^Bj toPSj
FSM to B 2 = B 2 to Subject
S to L j = A to L 2 = L 2 t o Subject = 22cm
PS is mobile
PS 2 is stationary
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Fig. 1. Schematic representation of Maxwellian
view system. S = source, a
rotating 1-mm pinhole,
peak wavelength 470 nm;
L, = collimating lens; A
= variable iris diaphragm;
B! = beam splitter; L2
= Maxwellian view lens; B2
= beam splitter; VC = video
camera; FSM = front surface mirror; AR = alignment ring; PSi, PS2 = point
sources.
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RETINAL FIXATION POINT LOCATION / Zeffren er ol
head was obtained with a dental bite-bar mounted on
a compound vice mobile in three planes. To insure
the subject was properly aligned to the apparatus, a
third channel provided a closed-circuit video view of
the pupil entry location of the rotating beam and the
corneal reflection of alignment ring AR (a circle of
infrared light-emitting diodes concentric with the optical axis of the apparatus). The video view of the
rotating beam was obtained by deflecting some of the
beam from source S at beam splitter B2 onto a front
surface mirror (FSM; optically conjugate with the
subject's entrance pupil) and back through beam
splitter B2 into the video camera. The video view of
alignment ring, AR, was obtained by reflection off the
subject's cornea back into the apparatus and reflection at beam splitter B2 into the video camera. By
continually observing the information on the monitor, the experimenter could maintain subject/apparatus alignment by adjusting the position of the compound vice.
Subjects
We assessed 26 eyes in 14 healthy subjects ranging
in age from 11-54 yr. There were 11 male and three
female subjects, all with corrected vision of 20/25 or
better.
Protocol
The purpose and methods of the experiment were
explained to the subject, and informed consent was
obtained. To familiarize the subjects with the experimental task, each was shown enlarged prints of fluorescein angiograms of several retinas having: (1) classic FAZs and (2) "variant FAZs" containing capillaries crossing the fovea in various patterns.11"12 After
the subject was familiar with what they might see in
their own eyes, a bite bar was made, and the subject
was aligned to the optical axis of the apparatus.
Subjects, while carefully fixating point source PS2
used a joystick to move the guidelight (point source,
PSi) to at least 12 locations along the borders of their
FAZ. At each location the subject centered the guidelight on the capillary defining the FAZ border and
pushed a button signaling the pen to drop on the X-Y
plotter, thus making a dot outline of the FAZ. After
exiting the optical system, subjects were shown their
"dot pattern" and instructed to connect the dots by
hand adding as much detail as possible to form their
final FAZ tracing. The subject then marked on the
FAZ tracing the location of the fixation point. We
thus obtained a hard-copy replica of the subject's
FAZ to serve as the raw data for our future analyses.
If there were vessels crossing the "FAZ," the subject
was asked to mark dots along the vessels they saw
near their center of fixation and subsequently connect the dots free hand again, adding as much detail
as possible to form their final tracing.
Results
All of the subjects easily saw the Purkinje image of
their retinal capillaries. Ten of the 14 subjects
graphed details of the shadow of their FAZ in both
eyes and two (due to personal time constraints), in
only one eye. Another subject observed a traditional
FAZ in one eye but saw capillaries running through
what should have been the FAZ in the other, and one
subject saw. capillaries running through the fixation
point in both eyes. Figure 2 depicts a sample of the
various FAZ tracings obtained. Panel A displays the
tracing of one of only three eyes with a retinal point
of fixation located in the geographic center of the
FAZ as classically described anatomically. Panel B
displays a tracing from an eye with the retinal point of
fixation located a typical distance from the geographic center of the FAZ, and Panel C displays the
tracing of the subject with the largest distance (189
p ) between the retinal point of fixation and the
geographic center of the FAZ. Panel D displays the
tracing of one of three eyes with vessels in the retinal
area more commonly occupied by the FAZ. Even by
casual observation, it becomes clear that the FAZ
boundaries are not always concentric with the fixation point (Panel B and C).
Although classically described as circular, the FAZ
is irregular in size and shape (Fig. 2). This irregularity
in size and shape complicates the objective determination of the center of the FAZ. To solve this problem, a geographic "center" was defined in the following manner (Fig. 3). First, the largest possible rectangle having all four corners located inside the borders
of the FAZ tracing was aligned such that the horizontal dimension of the rectangle was parallel to the horizontal axis of the tracing. Second, as illustrated in
Figure 3A, distances from each side of the rectangle
(labeled h, h', v, and v') to the traced FAZ border were
measured at each of five equally spaced locations
along each side of the rectangle (lines labeled v,-v5,
v'i-v'5, hj-h5, and h',-h'5). Third, as illustrated in Figure 3B, each of the four subsets of distances were
averaged [eg, (h, + h2 4- h3 + h4 + h5)/5 = hx and (h',
+ h'2 + h'3 + h'4 + h'5)/5 = h'x], and these averages
were added to the appropriate end of the horizontal
or vertical dimension of the initial rectangle (dashed
rectangle) to yield a new rectangle (solid rectangle)
with a total horizontal dimension of H and total vertical dimension of V (ie, H = h + hx + h'x and V = v
+ vx + v'x)- The geographic center of the FAZ was, in
turn, defined as the point GC formed by the crossing
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INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / Ocrober 1990
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100 \L
A. CENTERED
B. TYPICAL
C. LARGEST
D. ATYPICAL
of a vertical line bisecting H and a horizontal line
bisecting V (Fig. 3b).
All 23 eyes with FAZs had retinal fixation points
located in the FAZ. However, only three eyes from
three different subjects had their retinal points of fixation located at the geographic center of the FAZ.
Vectors defining the distance from the geographic
center of the FAZ to the subject's fixation point and
the direction of deviation (with 0° being horizontal to
the right) were determined for each FAZ tracing.
These distances were then converted to retinal distances using the Gullstrand reduced model eye with a
nodal-point to retina distance of 16.67 mm, after
Fig. 2. Four FAZ tracings. (A) Classic FAZ tracing with centered fixation
point; (B) FAZ tracing
showing a typical eccentric
location for the retinal point
of fixation; (C) FAZ tracing
showing the largest eccentric distance between the
geographic center of the
FAZ and the retinal point of
fixation; (D) Tracing showing no FAZ and retinal capillaries near the retinal point
of fixation. ""Center of fixation; 4- geographic center of
FAZ.
compensating for the optical magnification factor of
the Maxwellian view optical system and the gain of
the X-Y plotter. Figure 4 uses a polar-coordinate system to illustrate the location of the retinal point of
fixation relative to geographic center of the FAZ for
each eye tested. Although the data as a whole tends to
cluster near the origin (ie, the retinal point used for
fixation tended to be nearer the center of the FAZ
compared with the edge of the FAZ), the distribution
of directions of deviation appear random. The largest
deviation of the retinal point of fixation from the
geographic center of the FAZ was 189 /*m. The average deviation from the geographic center across all
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RETINAL FIXATION POINT LOCATION / Zeffren er ol
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B
A
V
5
\
V
"2
H
h,
\
.__
1
=—^
'2
v
V
3
4
Fig. 3. Schematic illustrating the method for determining the geographic center of the FAZ. Panel A illustrates a hypothetical FAZ
containing the largest possible rectangle (sides labeled h, h', v, and V) and distances to the FAZ border measured at 5 equally spaced points
along each side of the rectangle. Panel B illustrates the solid rectangle defined by adding the average distance to the FAZ border for each side
(hx, hx, vx, and v'x) to h, h', v, and v* denning a new rectangle with sides of length H and V. The geographic center of the FAZ(GC) is defined as
the intersection of bisectors of H and V.
subjects was 66.50 Aim. There was no tendency for the
eccentricity of the retinal point of fixation to increase
with increasing FAZ diameter.
Discussion
Our data indicate that the retinal point of fixation
deviates from the geographic center of the FAZ by
about 65 nm (standard deviation, ± 50 jum) with a
120
210
330
300
270
Fig. 4. Location of the retinal point of fixation from the geographic center of the FAZ tracing for each eye tested. Left eyes are
represented by open circles; right eyes are represented by closed
circles. Irregular circular pattern represents a typical FAZ border.
Angles are shown in degrees; distances are given in microns.
Fig. 5. Location of the retinal point offixation(solid circles) from
the geographic center of the FAZ tracing for each eye tested. Lightly
shaded area represents the area at risk of damage from a single
200-/xm or 100-/xm laser burn (darkly shaded circles) placed to
overlap a lesion 200-jum from the center of the FAZ by 100-jum.
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INVESTIGATIVE OPHTHALMOLOGY b VISUAL SCIENCE / October 1990
range of 0-190 /urn. These findings suggest that laser
burns centered on retinal points less than 300 ^m
from the geographic center of the FAZ run a significantly higher risk of falling directly on or nearer to
the retinal point of fixation than intended. Furthermore, the risk of burning the point of fixation can
markedly increase as burns are placed closer to the
geographic center of the FAZ. The implications of
this finding are profound and find support in current
literature.
To illustrate, assume that, as in recent clinical
trials,6"9 retinal lesions up to 200 ^m from the FAZ
center are treated with burns which overlap the lesion
by up to 100+ jum. Furthermore, grant that our data
form a representative sample of the population for
the location of the retinal point of fixation with respect to the geographic center of the FAZ (data
points, Fig. 5). With these assumptions, six of 24 eyes
(25%) have retinal points of fixation which are potentially vulnerable to being burned (Fig. 5, lightly
shaded area). However, since photocoagulation treatment is generally limited to or slightly overlaps the
area of frank pathology (eg, neovascular membrane
or histospot), it is likely that a series of burns will be
placed only in the sector of the macular area containing the site of the lesion (Fig. 5, darkly shaded area
schematically shows both a 200- and 100-/um burn).
Under these criteria and if the treatment sector of the
macular area is limited to 90°, it is likely that for any
one particular series of burns one or two eyes of our
sample of 24 (4%-8%) would have their retinal point
of fixation adversely effected by photocoagulation
therapy.
The obvious question arises as to what percentage
of treatment failures (loss of six lines of visual acuity
or more at first follow-up) can be accounted for by
variations in the location of the point of fixation with
respect to the geographic center of the FAZ. Although
we cannot answer this question definitively with the
data collected to date, it is interesting to note that
with argon treatment it has been reported that 9% of
eyes treated for neovascular maculopathy,6 9% of the
eyes treated for macular area ocular histoplasmosis,7
and 10% of those eyes treated for macular area idiopathic neovascularization8 lost six or more lines of
visual acuity at first follow-up despite "successful"
treatment of the pathology. This order of magnitude
of initial follow-up failure is not unique to argon
treatment. Studies using krypton therapy for histoplasmosis have reported a similar percentage of patients (8%) with a six-line loss in visual acuity at first
follow-up.9 The argument is further fueled by the fact
that the best predictor of visual acuity loss, despite
adequate therapy, is treatment proximity to the
center of the FAZ.20 When analysis is limited to eyes
Vol. 31
with lesions within 375 ^m of the FAZ center between 8%—33% of the eyes successfully treated lost six
lines or more at first follow-up depending on the particular study.6"9 Although this could be accounted for
by assuming that pathology within 375 ixm is more
likely to affect the retinal point of fixation, our data
suggest another possibility. Given the uncertainties of
thermal spread, dose specification, actual spot size in
the plane of the retina, variation in pigment absorption, and accuracy of burn placement with respect to
desired location, the speculative estimate of 4%-8%
may indeed be an underestimate of the number of
retinal fixation points at risk. Simply allowing for 50
/im of uncertainty would raise the number of retinal
fixation points at risk from 4%-8% up to 16%-20%.
To the extent this analysis is correct, it suggests that
therapeutic failures at first visit for eyes with retinal
lesions between 200-375 jum could be reduced by as
much as 20% by using the actual retinal point of
fixation as a reference as opposed to the geographic
center of the FAZ. This, in turn, raises the issue of
developing a clinically accurate technique for locating the retinal point of fixation.
In the unparalyzed eye having good visual acuity
the retinal point used for fixation is relatively easy to
identify.21 If techniques are adopted to paralyze the
eye which do not compromise vision, then it would
be a relatively easy to have the patient move a small
fixation point (eg, with a joy stick), which is also
visible to the clinician superimposed on the patient's
fundus, until the fixation point is exactly centered
over the patient's retinal point of fixation.
Unfortunately, with a visual acuity loss the patient
may or may not be using their "normal" (prepathology) retinal point of fixation, and the procedures
outlined above may or may not be appropriate. Yet,
since visual acuity has been reported to recover, it
remains important to identify the retinal point of fixation used before loss of visual acuity and avoid this
retinal location during therapy. The uncertainty can
be reduced, if not eliminated, by identifying the location of the retinal point of fixation in at-risk eyes (eg,
confluent drusen,22"26 loss of absolute sensitivity,25"29
acquired tritan errors,30"32 or loss of vision in fellow
eye3334 in age-related maculopathies) before vision
loss and using this point as the reference should therapy be needed at a later date.
Our data indicate the retinal point of fixation is not
always centered in the FAZ. Furthermore, the deviations of the retinal point of fixation from the center of
the FAZ can be large enough to jeopardize the retinal
point of fixation during foveal area laser photocoagulation therapy which avoids the center of the FAZ
compared with locating and avoiding the retinal
point of fixation. This risk can be reduced by using
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RETINAL FIXATION POINT LOCATION / Zeffren er ol
No. 10
the retinal point of fixation as the reference for foveal
area photocoagulation rather than the center of
the FAZ.
Key words: retinal fixation point, foveal avascular zone
(FAZ), fovea, photocoagulation, Purkinje image
Acknowledgments
The authors thank Sherard Dorroh for his assistance in
data collection and Jana Harvey for her assistance in data
collection, analysis, word processing, and illustration preparation.
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