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RETINAL CAPILLARY DENSITY IN

PATIENTS WITH BIRDSHOT


CHORIORETINOPATHY
PHILIPP K. ROBERTS, MD,*† PETER L. NESPER, BA,* DEBRA A. GOLDSTEIN, MD,*
AMANI A. FAWZI, MD*

Purpose: To quantify retinal capillary density and determine its correlation with visual
acuity in patients with birdshot chorioretinopathy (BCR).
Methods: Patients with BCR and age-matched controls were imaged using a commer-
cially available spectral domain optical coherence tomography angiography system
(RTVue- XR Avanti; Optovue, Inc). We used the integrated software of the optical coherence
tomography angiography device to analyze the foveal avascular zone area and the capillary
density in the full retina as well as in the superficial capillary plexus and deep capillary
plexus. We assessed the correlation between these parameters and visual acuity.
Results: Seventy-four eyes of 42 study participants (37 eyes of 21 BCR and 37 eyes of
21 healthy subjects) were included in this observational cross-sectional study. Capillary
density of the full retina, superficial capillary plexus, and deep capillary plexus were
significantly decreased in BCR compared with the healthy control group (P , 0.01). Visual
acuity in patients with BCR was significantly associated with the capillary density of the
superficial capillary plexus, deep capillary plexus, and full retina (P , 0.01) but not with the
area of the foveal avascular zone.
Conclusion: The decrease in visual acuity in patients with BCR is associated with retinal
vascular impairment. Vessel density of the retinal capillary plexuses may be a promising
imaging biomarker for BCR disease severity.
RETINA 0:1–8, 2017

B irdshot chorioretinopathy (BCR), first described in


1980 by Ryan and Maumenee, is a chronic bilateral
disease, commonly affecting middle-aged, otherwise
well as retinal vasculitis and arteriolar narrowing, and
is highly associated with the HLA-A29 haplotype. It
has been hypothesized that inflammation in BCR
healthy patients.1,2 Symptoms typically include floaters, evolves independently in the choroid and retinal
nyctalopia, photopsias, decreased color vision, and vessels.5,6 Sequelae of the disease include diffuse
blurred vision.2,3 Although the pathologic mechanisms photoreceptor loss, cystoid macular edema (50%),
underlying BCR are not fully understood, it is generally epiretinal membranes (ERMs) (8%), and choroidal
considered an autoimmune disorder.4 neovascularization (5%–7.5%).2,7
Clinically, it is characterized by bilateral yellow- Fluorescein angiography is considered the gold
white choroidal lesions, mild vitreous inflammation as standard imaging modality for retinal vascular manifes-
tation of BCR, highlighting findings of vasculitis,
From the *Department of Ophthalmology, Feinberg School of
Medicine, Northwestern University, Chicago, Illinois; and †Depart- subclinical retinal capillary occlusion, or vascular hyper-
ment of Ophthalmology and Optometry, Medical University of permeability.8,9 As it is a strictly two-dimensional imag-
Vienna, Vienna, Austria. ing modality, it is not possible to be aware of the
The Department of Ophthalmology, Northwestern University,
Feinberg School of Medicine receives unrestricted financial support different retinal capillary plexuses on fluorescein angi-
from Research to Prevent Blindness. Research instrument support ography, precluding the distinction of ischemia at dif-
was provided by Optovue, Inc, Fremont, California. This work was
partly supported by NIH DP3DK108248 (A.A.F.).
ferent levels within the retina.10 Furthermore, although
None of the authors has any conflicting interests to disclose. fluorescein angiography has the advantage of imaging
Reprint requests: Amani A. Fawzi, MD, Department of Ophthal- dye leakage as evidence of breakdown of the blood–
mology, Feinberg School of Medicine, Northwestern University,
645 N. Michigan Ave, Suite 440, Chicago IL 60611; email: retinal barrier, this feature also carries the disadvantage
afawzimd@gmail.com of obscuring underlying anatomical detail.

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2 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2017  VOLUME 0  NUMBER 0

With this in mind, we chose to use the new and purpose of this study, angiographic en face OCT mea-
noninvasive optical coherence tomography angiography suring 3 mm · 3 mm (x · y) were evaluated using the
(OCTA), a functional extension of conventional optical incorporated Angiovue software. For detection of blood
coherence tomography (OCT). Optical coherence flow, the device acquires two consecutive B-scans at the
tomography angiography shows the retinal and choroi- same position to differentiate between bulk tissue and
dal vasculature by detection of blood flow within the fluctuating particles (mostly erythrocytes in the blood
vessels, while also depicting the retinal microstructure stream). The machine uses split-spectrum amplitude-
three dimensionally (like conventional OCT). Previous decorrelation angiography to improve the performance
studies have used OCTA to qualitatively characterize of the vessel segmentation algorithm. For the purpose
BCR eyes; however, significant questions remain of selecting images with a high enough image quality,
regarding the quantitative changes at the different we used the signal strength index, a measure automat-
retinal capillary plexuses and their impact on visual ically displayed with every volume scan. Images with
acuity (VA).11 The aim of this study was to use a signal strength index below 50 were not included in
OCTA to quantify the alterations in the different retinal our analysis.
capillary plexuses and their impact on VA in patients
with BCR.
Assessment of Capillary Density, Retinal Thickness,
and Foveal Avascular Zone
Methods We used the integrated analytics software (version
2016.1.0.26) of the Angiovue device to evaluate the
Study Participants vessel density, retinal thickness, and foveal avascular
The study protocol and procedures adhered to the zone (FAZ). We used the preset segmentation of the
ethics tenets of the Declaration of Helsinki and were superficial capillary plexus (SCP), where the inner and
approved by Northwestern University’s Institutional outer boundaries are set 3 mm posterior to the internal
Review Board. Informed consent was obtained from limiting membrane and 15 mm posterior to the inner
each participant before inclusion in this retrospective plexiform layer (IPL), respectively. In eyes with an
observational cross-sectional study. Healthy control ERM, the internal boundary was set 3 mm posterior
participants and participants diagnosed with BCR were to the ERM and not the internal limiting membrane.
recruited at the Department of Ophthalmology of the However, because the posterior boundary of the seg-
Feinberg School of Medicine at Northwestern Univer- mentation was dependent on the position of the IPL,
sity, Chicago, IL. Inclusion criteria for the BCR cohort the slab included the entire SCP and manual adjust-
were consistent with the international consensus confer- ment of the anterior boundary was not necessary.
ence research criteria for the diagnosis of BCR.12 All For the deep capillary plexus (DCP), the inner and
patients were HLA-A29 positive. Eyes were not outer boundaries are set 15 mm posterior to the IPL and
included in this study if they did not meet the criteria, 70 mm posterior to the IPL, respectively. To evaluate
had opacified ocular media, or low quality imaging the vasculature of the entire retinal thickness, the inner
preventing a detailed analysis of retinal capillary boundary was set at 3 mm posterior to the internal
plexuses. All patients had been diagnosed by a single limiting membrane (in cases with an ERM this was 3
uveitis specialist (D.A.G.) and were followed regularly mm posterior to the ERM), and the outer boundary was
for BCR at Northwestern University including manually set at the outer nuclear layer, posterior to the
best-corrected VA (BCVA) testing, complete ocular DCP. Depending on the retinal anatomy, the offset from
examination, OCT imaging, color fundus photography, the IPL differed individually, however, was always
electroretinography, and Goldmann visual fields. placed within the outer nuclear layer and anterior to
the hyperreflective retinal pigment epithelium. We as-
sessed SCP, DCP, and full retinal vessel densities for
Imaging
the whole en face image (3 · 3 mm) as well as for the
For OCTA imaging and evaluation, a commercial parafoveal area (ring with a diameter of 3 mm of the
spectral domain OCT device (RTVue- XR Avanti; outer circle and a diameter of 1 mm of the inner circle).
Optovue, Inc, Fremont, CA) was used. The OCT uses The FAZ area was measured using the nonflow
a light beam with a center wavelength of 840 nm and detection algorithm integrated in the analysis software.
a full-width half maximum of 45 nm operating at an By clicking into the center of the FAZ in the en face
axial scan rate of 70.000 A-scans per second. The angiographic image of the SCP, the software automat-
OCTA volume scans consisted of 304 · 304 · 512 ically extends the measured area to the vessels
voxels and were acquired in 2.9 seconds. For the surrounding the FAZ (Figure 1).

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RETINAL CAPILLARY DENSITY IN BCR  ROBERTS ET AL 3

Fig. 1. Color fundus photography


(A) and OCTA en face maps (B–F)
of the left eye of a healthy control
participant showing vessel density
maps of the SCP (B), the deep
capillary plexus (C), and the full
retina (D). The dashed white square
in (A) illustrates the location of the
OCTA en face images (B–F). The
color legend illustrates vessel den-
sity in percentage. The blue overlay
on the en face OCTA of the SCP
(E) shows the foveal zone (central
circle with 1 mm diameter) and the
parafoveal zone (ring surrounding
the foveal zone with a 3 mm
diameter). The FAZ, automatically
measured by the OCTA device, is
highlighted in yellow in F.

Retinal thickness was automatically measured as the Superficial capillary plexus, DCP, and full retinal
distance between the internal limiting membrane and vessel density were significantly lower in the BCR
the retinal pigment epithelium for the foveal (circle group compared with healthy controls. A significant
with a diameter of 1 mm) and parafoveal areas. difference was observed in the parafoveal retinal
thickness between BCR and healthy controls but not
Statistics in foveal retinal thickness. Details are presented in
Table 2.
We used IBM SPSS statistics version 21 (IBM The vessel densities of the SCP, DCP, and full retina
SPSS Statistics, IBM Corporation, Chicago, IL). The showed a significant (negative) correlation with
Shapiro–Wilk test was used to test for normal distri- BCVA (logarithm of the minimal angle of resolution)
bution of the parameters. We used a Mann–Whitney U in patients with BCR. In the control eyes, there was no
test to compare the FAZ area, retinal thickness, and the significant correlation between BCVA and any of the
vessel densities of the SCP, DCP, and full retina following parameters: vessel density, FAZ area,
between the BCR and the control group. We used foveal, and parafoveal retinal thickness (Table 3).
Spearman correlation analysis to study the correlations
between VA and the following parameters: BCR dis-
ease duration, capillary density, FAZ area, and retinal Discussion
thickness. For these analyses, VA was converted from
Snellen to the logarithm of the minimal angle of In this study, we used OCTA to quantitatively
resolution. analyze vessel densities of the retinal capillary plex-
uses in eyes with BCR and assess their correlation
with VA. We found that the SCP and DCP vessel
Results densities were significantly reduced in eyes with BCR
when compared with an age-matched control group
Our study included 74 eyes of 42 study participants (Table 2). Vessel density in the different capillary
(28 women, 14 men) with a mean age of 58 years (±9 plexuses was significantly associated with VA in pa-
[SD]). Overall demographic and clinical characteristics tients with BCR. This was not the case in the healthy
are presented in Table 1. control group (Table 3). The FAZ area and foveal
Representative examples of retinal capillary density retinal thickness were not significantly different
and FAZ area are presented in Figures 2–4. between BCR and healthy controls. The parafoveal
Patients with BCR had a mean disease duration of 6 retinal thickness, however, was significantly thinner
years (±3.5 SD). Twenty-four eyes had an ERM, eight in the BCR group (Table 2). There were no significant
eyes had cystoid macular edema, two eyes had a cho- correlations in either the BCR or healthy control
roidal neovascularization, and one eye had subretinal groups between VA and any of the following param-
fluid associated with cystoid macular edema. All eters: FAZ area, foveal, or parafoveal retinal thickness
except for two study patients with BCR (three study (Table 3).
eyes) were receiving either local or systemic therapy The different retinal vascular plexuses show a non-
including corticosteroids as well as other immunomo- uniform capillary distribution, which might be attrib-
dulators (Table 1). uted to the metabolic demands of adjacent retinal

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4 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2017  VOLUME 0  NUMBER 0

Table 1. Characteristics of Study Participants used OCTA in a series of four patients with BCR to
Healthy
show flow-void areas in the choroid in birdshot lesions
Control Patients and changes in the full retinal capillary network. The
Participants With BCR retinal capillary changes detected in their study
(n = 21) (n = 21) included abnormally tortuous vessels, capillary loops,
Female, n (%) 12 (57) 16 (76) focal dilatations, and an increased intercapillary space,
Eyes (n) 37 37 features typically seen in later stages of vasculitis.11,16
Age (mean ± SD), years 58 ± 9 57 ± 8 This meticulous evaluation of microangiographic
Visual acuity (mean ± SD), 0.01 ± 0.06 0.10 ± 0.20 changes in the retina is, however, subjective in nature
logMAR
(Mean Snellen equivalent) (20/20) (20/25) and would be challenging and time consuming to per-
Systemic IMT, n = patients 0 13 (62) form in clinical practice as well as for the larger num-
(%) ber of eyes and for the different retinal capillary
Local treatment, n = eyes (%) plexuses. Therefore, we decided to use a quantitative
Fluocinolone acetonide 0 23 (62) and automated approach to assess microvascular dam-
implant
PST triamcinolone 0 17 (46) age. In our study, capillary density in the SCP, DCP,
acetonide and the full retina was significantly decreased in the
Prednisolone acetate eye 0 8 (22) BCR group, suggesting that microvascular inflamma-
drops tion and subsequent capillary closure are present
Dexamethasone 0 3 (8) throughout the retinal vasculature and not confined
intravitreal implant
IVTA 0 2 (5) to a particular network in this disease.
Anti-VEGF 0 1 (3) In a histopathological study of BCR eyes, Gaudio
No treatment 0 3 (8) et al6 showed foci of lymphocytic aggregations along
Eye findings, n = eyes (%) retinal vessels, but did not specify in which layer of the
ERM 0 24 (65) retina these were most numerous. They hypothesized
CME 0 8 (22)
CNV 0 2 (5) that a progression from these perivascular lymphocytic
SRF 0 1 (3) infiltrations to ischemia of the inner retina might be
anti-VEGF, anti–vascular endothelial growth factor; CME,
expected in patients with BCR in later stages of the
cystoid macular edema; CNV, choroidal neovascularization; IMT, disease. In our series, we found a significant decrease
immunomodulatory therapy; IVTA, intravitreal triamcinolone of the retinal capillary density as well as retinal thick-
acetonide injection; logMAR, logarithm of the minimal angle of
resolution; PST triamcinolone acetonide, posterior subtenon
ness in the parafoveal area in eyes of patients with BCR
injection of triamcinolone acetonide; SRF, subretinal fluid. (with a mean disease duration of 6 years), which seems
to support their hypothesis. Recently, Agrawal et al17
measured retinal vascular calibers in patients with BCR
tissue.13 It has been hypothesized that different vascu- and reported significantly impaired calibers only in the
lar diseases could affect capillary networks differently, retinal venules compared with a healthy control group.
prompting us to separately examine the SCP and DCP This finding suggests that microvascular inflammatory
in our study.14,15 In a recent study, de Carlo et al11 damage in BCR is primarily present in the venous arm.

Fig. 2. Color fundus photogra-


phy (A) and OCTA en face
maps (B–F) of the right eye of
a patient with BCR showing
vessel density maps of the SCP
(B), the deep capillary plexus
(C), and the full retina (D). The
dashed white square in (A) il-
lustrates the location of the
OCTA en face images (B–F).
Note the pronounced choroidal
changes surrounding the optic
disk in A, as well as the almost
confluent appearing birdshot
lesions. Mild changes in vessel
density are observed in B–D.
The en face angiographic scans
(E,F) do not show obvious
morphological changes of the
retinal capillaries or the FAZ. The color legend illustrates vessel density in percentage.

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RETINAL CAPILLARY DENSITY IN BCR  ROBERTS ET AL 5

Fig. 3. Color fundus photography


(A) and OCTA en face maps (B–
F) of the right eye of a patient with
BCR showing vessel density maps
of the SCP (B), the deep capillary
plexus (C), and the full retina (D).
The dashed white square in (A)
illustrates the location of the
OCTA en face images (B–F).
Classic creamy ill-defined birdshot
lesions appearing to radiate from
the optic nerve are seen in A, as are
a few more atrophic lesions nasal
to the nerve. Moderate changes in
vessel density are noted in B–D.
The color legend illustrates vessel
density in percentage. Note the
telangiectatic vessels temporal to
the fovea in the SCP in E and F.

Foveal retinal thickness was not significantly dif- present in the fovea secondary to subtle capillary leak-
ferent between the BCR and healthy control group in age in BCR. The actual foveal retinal tissue thickness
our study, nor was the FAZ area. However, parafoveal may, therefore, be thinner in patients with BCR than in
retinal thickness was significantly decreased in the healthy controls but this might not be obvious due to
BCR eyes. Retinal thinning in this area may be caused overall retinal (noncystic) swelling.
by retinal atrophy secondary to capillary loss in the The BCVA was significantly correlated with capil-
macula. Because the fovea contains no inner retinal lary density in the SCP, the DCP, and the full retina in
layers and, therefore, no capillary network, the foveal the BCR group. In the healthy control group, however,
zone (circle with a 1 mm diameter) may be less we did not observe a significant correlation between
susceptible to retinal vasculitis and subsequent retinal VA and retinal capillary densities. Previous studies in
atrophy. The choroidal perfusion could be sufficiently BCR have shown disruption of photoreceptor bands
robust to support the fovea, which would explain the and outer retinal atrophy on OCT associated with
nonsignificant difference in foveal retinal thickness vision loss.2,18–21 An association of photoreceptor
between the groups in this study. Furthermore, the layer disruption on OCT with retinal vasculitis has
presence of intraretinal cysts and/or an ERM is likely been suggested.21 These findings might be explained
to distort the foveal contour, resulting in thickening of by the important role of the DCP in maintaining a func-
the fovea in the BCR eyes. In fact, when we compared tional outer retinal metabolism. Recently, our group
the healthy controls and BCR eyes (excluding eight has shown an association between DCP nonperfusion
eyes with cystoid macular edema), the mean foveal and photoreceptor disruption in patients with diabetic
thickness in both groups was surprisingly similar macular ischemia, highlighting the important role of
(259.9 ± 31.3 vs. 259.9 ± 32.4 mm). An important the DCP for oxygen needs of the outer retina.14 In
consideration, however, is that diffuse retinal thicken- BCR, the correlation between vessel density and VA
ing without the presence of intraretinal cysts may be may be caused by one of the following mechanisms or

Fig. 4. Color fundus photogra-


phy (A) and OCTA en face maps
(B–F) of the right eye of
a patient with BCR with late-
stage disease showing vessel
density maps of the SCP (B), the
deep capillary plexus (C), and
the full retina (D). The dashed
white square in (A) illustrates
the location of the OCTA en
face images (B–F). Pigmentary
changes can be observed in and
around the macula in A. Distinct
birdshot lesions are harder
to appreciate, and the retina
appears atrophic. Vessel density
is severely impaired in the cap-
illary plexuses (B–D). The color legend illustrates vessel density in percentage. Note the capillary dropout and the distorted FAZ in the SCP in E and F.

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6 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES  2017  VOLUME 0  NUMBER 0

Table 2. Vessel Density, Area of FAZ, and Retinal Thickness in the BCR and Control Group
Healthy Controls (37 Eyes) Patients With BCR (37 Eyes) P
Vessel density (mean ± SD), %
SCP 50.41 ± 3.01 46.39 ± 4.03 ,0.01*
SCP parafovea 52.87 ± 3.05 48.32 ± 4.58 ,0.01*
DCP 55.90 ± 3.14 51.64 ± 4.09 ,0.01*
DCP parafovea 59.14 ± 3.22 54.37 ± 4.44 ,0.01*
Full retina 53.09 ± 3.27 48.97 ± 4.58 ,0.01*
Full retina parafovea 56.05 ± 3.29 51.35 ± 5.09 ,0.01*
FAZ area (mean ± SD), mm2 0.275 ± 0.10 0.244 ± 0.10 0.196
Retinal thickness (mean ± SD), mm
Fovea 259.9 ± 31.3 283.7 ± 104.0 0.417
Parafovea 319.1 ± 16.5 306.1 ± 62.0 ,0.01*
The foveal area was defined as a circle with a diameter of 1 mm centered on the fovea. The parafoveal area was defined as a ring with
a diameter of 3 mm surrounding the foveal area.
*Statistically significant differences between the groups.

a combination of these. Since the plexiform layers of rioration in patients with BCR. Previous studies, how-
the retina are known to be highly metabolizing regions ever, based on indocyanine green angiography, OCT,
and dependent on sufficient oxygen supply, retinal and histopathology have suggested that there may be
vascular impairment could lead to ischemia and sub- differential inflammatory involvement of the retina
sequent dysfunction of signal transmission within the and choroid in BCR.5,6,20 Furthermore, current spec-
parafoveal inner retina.22 Another possibility is that, tral domain-OCT–based OCTA devices have limited
although primarily nourished by the choroidal vascu- penetration depth into the choroid, making an accurate
lature, foveal cones may be dependent on lateral dif- evaluation of miniscule abnormalities particularly
fusion of oxygen from the surrounding retinal capillary challenging.11 For these reasons, we think that future
plexuses.23 Finally, it is plausible that there is no direct studies using swept-source OCT-based OCTA oper-
cause-and-effect relationship between VA and retinal ating at longer wavelengths are necessary to compre-
vessel density. In this scenario, retinal vessel density hensively investigate the relationship between retinal
may be a significant, but indirect biomarker for global and choroidal vascular damage.
retinal damage including photoreceptor compromise, There was no significant difference in the FAZ area
caused by the underlying inflammatory mediators in between the two groups. This finding stands in
BCR. We cannot rule out that choriocapillaris and contrast to other retinal vascular diseases such as
choroidal changes, which we did not assess in this diabetic retinopathy or retinal vein occlusion, where
study, could account for photoreceptor and VA dete- enlargement of the FAZ is a typical finding that is

Table 3. Correlation Between Disease Duration, Vessel Density, FAZ Area, Retinal Thickness, and Visual Acuity (logMAR)
Healthy Controls (n = 37) BCR (n = 37)
Correlation of Visual Acuity With
Evaluated Retinal Parameters R P R P
Disease duration — — 0.184 0.276
Vessel density
SCP 20.117 0.492 20.503* ,0.01*
SCP parafovea 20.120 0.478 20.527* ,0.01*
DCP 20.144 0.396 20.506* ,0.01*
DCP parafovea 20.189 0.263 20.463* ,0.01*
Retinal vessel density 20.162 0.339 20.516* ,0.01*
Retinal vessel density parafovea 20.164 0.331 20.517* ,0.01*
FAZ area 20.135 0.425 0.127 0.455
Retinal thickness
Foveal retinal thickness 20.022 0.896 0.071 0.676
Parafoveal retinal thickness 0.021 0.902 20.117 0.490
The foveal area was defined as a circle with a diameter of 1 mm centered on the fovea. The parafoveal area was defined as a ring with
a diameter of 3 mm surrounding the foveal area.
*Statistically significant correlations.
logMAR, logarithm of the minimal angle of resolution.

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RETINAL CAPILLARY DENSITY IN BCR  ROBERTS ET AL 7

associated with structural damage to inner and outer tomography, optical coherence tomography angiogra-
retinal layers.14,24 The FAZ area in the general pop- phy, vessel density.
ulation, however, is highly variable, which may
reduce the predictive value of this parameter for an References
individual patient.25 Using the implemented software
1. Ryan SJ, Maumenee AE. Birdshot retinochoroidopathy. Am J
of the OCTA instrument for automated measurement
Ophthalmol 1980;89:31–45.
of the FAZ, we observed FAZ area sizes in both 2. Minos E, Barry RJ, Southworth S, et al. Birdshot chorioretinop-
groups that were similar to a recent report of healthy athy: current knowledge and new concepts in pathophysiology,
eyes by Shahlaee et al,26 who used a manual method diagnosis, monitoring and treatment. Orphanet J Rare Dis 2016;
for FAZ delineation in OCTA images. Given that the 11:61.
3. Crawford CM, Igboeli O. A review of the inflammatory chorior-
control and BCR groups were age matched in our
etinopathies: the white dot syndromes. ISRN Inflamm 2013;
study, we do not believe that age could have had 2013:783190.
any role as a potential confounder in the correlation 4. Kuiper J, Rothova A, de Boer J, Radstake T. The immunopatho-
between FAZ area and VA, a finding previously genesis of birdshot chorioretinopathy; a bird of many feathers.
shown in eyes with retinal ischemic vascular Prog Retin Eye Res 2015;44:99–110.
5. Herbort CP, Probst K, Cimino L, Tran VT. Differential inflam-
disease.24
matory involvement in retina and choroid in birdshot choriore-
We are aware of certain limitations of this study. tinopathy. Klin Monbl Augenheilkd 2004;221:351–356.
The cross-sectional observational study design limited 6. Gaudio PA, Kaye DB, Crawford JB. Histopathology of
our observations to only one point in time within the birdshot retinochoroidopathy. Br J Ophthalmol 2002;86:
disease process. As well, the study did not stratify 1439–1441.
7. Shah KH, Levinson RD, Yu F, et al. Birdshot chorioretinopathy.
patients with BCR based on disease severity, duration,
Surv Ophthalmol 2005;50:519–541.
or control. Larger, longitudinal studies would allow for 8. Levinson RD, Monnet D. Imaging in birdshot chorioretinopathy.
better understanding of the vascular pathology and the Int Ophthalmol Clin 2012;52:191–198.
chain of events that eventually lead to retinal damage 9. Adl MA, LeHoang P, Bodaghi B. Use of fluorescein angi-
and visual impairment, but the rarity of this diagnosis ography in the diagnosis and management of uveitis. Int
Ophthalmol Clin 2012;52:1–12.
may make this a difficult goal to achieve. Because of
10. Weinhaus RS, Burke JM, Delori FC, Snodderly DM. Compar-
the small field of view of the OCTA device (and ison of fluorescein angiography with microvascular anatomy of
focusing on correlations with VA), we only analyzed macaque retinas. Exp Eye Res 1995;61:1–16.
vessel densities in the macula in our study. We predict 11. de Carlo TE, Bonini Filho MA, Adhi M, Duker JS. Retinal and
that similar vascular damage occurs outside the choroidal vasculature in birdshot chorioretinopathy analyzed
using spectral domain optical coherence tomography angiog-
arcades, given electroretinographic findings and Gold-
raphy. Retina 2015;35:2392–2399.
mann visual field test results that are suggestive of 12. Levinson RD, Brezin A, Rothova A, et al. Research criteria for
global retinal functional changes,7 but repeated OCTA the diagnosis of birdshot chorioretinopathy: results of an inter-
measurements outside the macula are necessary to national consensus conference. Am J Ophthalmol 2006;141:
confirm this theory. Furthermore, exclusion of OCTA 185–187.
13. Chan G, Balaratnasingam C, Yu PK, et al. Quantitative mor-
scans of low quality and scans with severe motion
phometry of perifoveal capillary networks in the human retina.
artifacts may have led to exclusion of the most severe Invest Ophthalmol Vis Sci 2012;53:5502–5514.
cases of BCR. Strengths of our study include a rather 14. Scarinci F, Nesper PL, Fawzi AA. Deep retinal capillary non-
large number of study eyes, an age-matched control perfusion is associated with photoreceptor disruption in diabetic
group, and automated analyses. macular ischemia. Am J Ophthalmol 2016;168:129–138.
15. Park JJ, Soetikno BT, Fawzi AA. Characterization of the middle
In conclusion, our study showed decreased capillary
capillary plexus using optical coherence tomography angiography
density in all retinal vascular plexuses in eyes with in healthy and diabetic eyes. Retina 2016;36:2039–2050.
BCR compared with healthy controls, a finding which 16. Ali A, Ku JH, Suhler EB, et al. The course of retinal vasculitis.
was significantly correlated with BCVA in BCR. The Br J Ophthalmol 2014;98:785–789.
FAZ area was not different in eyes with BCR 17. Agrawal R, Joachim N, Li LJ, et al. Assessment of retinal
vascular calibres as a biomarker of disease activity in birdshot
compared with healthy controls and did not correlate
chorioretinopathy. Acta Ophthalmol 2016 Aug 6. doi: 10.1111/
with vision. Retinal capillary density measured auto- aos.13156. [Epub ahead of print].
matically by OCTA might be a promising new 18. Birch DG, Williams PD, Callanan D, et al. Macular atrophy in
parameter to monitor disease progression during birdshot retinochoroidopathy: an optical coherence tomogra-
follow-up and management of BCR and may be phy and multifocal electroretinography analysis. Retina 2010;
30:930–937.
a useful biomarker in future longitudinal studies.
19. Birnbaum AD, Fawzi AA, Rademaker A, Goldstein DA. Corre-
lation between clinical signs and optical coherence tomography
Key words: birdshot chorioretinopathy, capillary with enhanced depth imaging findings in patients with birdshot
plexus, deep capillary plexus, optical coherence chorioretinopathy. JAMA Ophthalmol 2014;132:929–935.

Copyright ª by Ophthalmic Communications Society, Inc. Unauthorized reproduction of this article is prohibited.
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20. Keane PA, Allie M, Turner SJ, et al. Characterization of birdshot 24. Balaratnasingam C, Inoue M, Ahn S, et al. Visual acuity is
chorioretinopathy using extramacular enhanced depth optical correlated with the area of the foveal avascular zone in dia-
coherence tomography. JAMA Ophthalmol 2013;131:341–350. betic retinopathy and retinal vein occlusion. Ophthalmology
21. Teussink MM, Huis In Het Veld PI, de Vries LA, et al. Multimodal 2016;123:2352–2367.
imaging of the disease progression of birdshot chorioretinopathy. 25. Shahlaee A, Samara WA, Hsu J, et al. In Vivo assessment of
Acta Ophthalmol 2016;94:815–823. macular vascular density in healthy human eyes using optical
22. Yu DY, Cringle SJ, Su EN, et al. Pathogenesis and intervention coherence tomography angiography. Am J Ophthalmol 2016;
strategies in diabetic retinopathy. Clin Exp Ophthalmol 2001; 165:39–46.
29:164–166. 26. Shahlaee A, Pefkianaki M, Hsu J, Ho AC. Measurement of
23. Birol G, Wang S, Budzynski E, et al. Oxygen distribution and foveal avascular zone dimensions and its reliability in healthy
consumption in the macaque retina. Am J Physiol Heart Circ eyes using optical coherence tomography angiography. Am J
Physiol 2007;293:H1696–H1704. Ophthalmol 2016;161:50–55.e51.

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