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com
Clinical science
▸ Additional supplementary
table and figures are published
online only. To view these files
please visit the journal online
(http://dx.doi.org/10.1136/
bjophthalmol-2012-302250).
Department of Ophthalmology,
Emory University School of
Medicine, Atlanta, Georgia,
USA
Correspondence to
Dr G Baker Hubbard,
Department of Ophthalmology,
Emory University School of
Medicine, 1365B Clifton Road,
N.E. Atlanta, GA 30322, USA;
ghubba2@emory.edu
Received 22 July 2012
Revised 30 October 2012
Accepted 7 November 2012
Published Online First
25 December 2012
To cite: Ray R,
Barañano DE, Hubbard GB.
Br J Ophthalmol 2013;97:
272–277.
272
Treatment of Coats’ disease with intravitreal
bevacizumab
Robin Ray, David E Barañano, G Baker Hubbard
ABSTRACT
Objective To compare the efficacy of intravitreal
bevacizumab plus ablative therapy with ablative therapy
alone for Coats’ disease.
Methods A retrospective review of all paediatric
patients who received treatment for Coats’ disease from
a single surgeon (GBH) from 1 January 2001 to 31
March 2010 was performed. Ten consecutive patients
who received intravitreal bevacizumab as part of their
treatment were matched to 10 patients treated with
ablative therapy alone by macular appearance, quadrants
of subretinal fluid, and quadrants of telangiectasias.
Outcomes evaluated were number of treatment sessions,
time to full treatment, and resolution of disease.
Results There was no statistical difference between
baseline characteristics when comparing the
bevacizumab and control groups. Eyes treated with
bevacizumab required more treatments over a longer
time period compared to the control group. All patients
in the bevacizumab group were successfully treated
while two of the patients in the control group failed
ablative techniques.
Conclusions Intravitreal bevacizumab may play a role
as adjuvant therapy in select cases of Coats’ disease, but
its use does not reduce the time to full treatment.
Resolution of disease was seen in the most severe cases
treated with bevacizumab plus thermal ablation whereas
their matched controls failed therapy with laser and
cryotherapy alone.
Coats’ disease is a sporadic, idiopathic, retinal vas-
cular disease usually found in young males.
Telangiectatic retinal vessels with aneurysms charac-
terise this disease. Abnormal permeability of these
vessels leads to exudative retinal detachment and
subretinal lipid deposits. Often subfoveal exudation
leading to permanent severe vision loss occurs
prior to presentation. The severe forms of the
disease often involve neovascular glaucoma and
phthisis bulbi.1
Initial treatment includes ablative therapy with
cryotherapy or laser photocoagulation to target the
areas of telangiectasias. Subretinal fluid (SRF) often
prevents adequate ablative therapy and it is not
uncommon for multiple treatment sessions to be
necessary to cause cessation of exudation.
Medical and surgical approaches to decrease the
amount of SRF have been studied with suboptimal
results. Intravitreal triamcinolone (IVTA) has been
administered in an attempt to moderate the break-
down of the blood ocular barrier. Though a
decrease of SRF was noted after treatment, several
of the patients developed proliferative vitreoretino-
pathy associated with rhegmatogenous retinal
detachment.2 Use of vitrectomy and scleral buckling
Ray R, et al. Br J Ophthalmol 2013;97:272–277. doi:10.1136/bjophthalmol-2012-302250
techniques with drainage of SRF have also been
reported.3 These techniques, however, carry signifi-
cant surgical risks and usually do not result in good
visual outcomes.
Vascular endothelial growth factor (VEGF) level
in ocular fluids (aqueous, vitreous and SRF) has
been shown to be elevated in Coats’ disease.4 5
VEGF plays an important role in the pathogenesis
of many retinal vascular diseases and its inhibition
effectively treats many of these diseases. Intravitreal
bevacizumab has been used as a treatment for
several VEGF-mediated diseases of the eye includ-
ing choroidal neovascular membranes, diabetic ret-
inopathy and retinal vein occlusions.6–8
Use of bevacizumab therefore has theoretical
benefits in Coats’ disease. If incompetence of the
vasculature can be alleviated, even temporarily, it
could be a useful adjuvant to care especially in eyes
with significant SRF. Case reports on bevacizumab
in Coats’ disease have shown promising efficacy in
decreasing the amount of SRF, macular oedema,
and exudate in this condition.5 9–21 Other
anti-VEGF agents have also been used as adjuvant
therapy with reported success.4 22 We describe our
experience with the use of intravitreal bevacizumab
for the treatment of this disorder and compare it to
standard ablative therapy.
METHODS
A retrospective review was performed of a single
surgeon’s (GBH) practice to identify children diag-
nosed with Coats’ disease who presented between 1
January 2001 and 31 March 2010. The search was
initiated using the Retcam (Clarity Medical
Systems, Inc., Pleasanton, California, USA) database
and only patients with fundus photography were
included. Medical records were reviewed and
patients who received intravitreal bevacizumab
combined with laser or cryotherapy for treatment
of the condition were identified and labelled as the
bevacizumab group. The remainder, who only
received ablative therapy (laser and/or cryotherapy),
were labelled as the control group. A change in
practice pattern occurred in May 2009 at which
point all patients were given intravitreal bevacizu-
mab as part of their treatment for Coats’ disease.
This was done based on several reports of efficacy
in treating the disease. Risks, benefits and alterna-
tives of therapy were outlined with patients/parents
and consent for off-label use of the medication was
obtained in all cases. Exclusion criteria included
patients over 17 years of age, patients who had
received intravitreal triamcinolone acetonide, eyes
without submacular exudates, eyes that had end-
stage disease at presentation and patients who
transferred care prior to completion of treatment.
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Clinical science

Eyes treated with bevacizumab plus laser and/or cryotherapy
were each matched to an eye in the control group based on
baseline macular appearance, quadrants of telangiectasias and
quadrants of SRF. This was done in a blinded fashion with the
physician performing the match (GBH) only having macular
photography and severity of disease at baseline for eyes in each
group. The outcome of patients was not available to the phys-
ician at the time of matching. Data from initial and follow-up
examinations including intraocular pressure, anterior segment
examination, and quadrants of SRF and telangiectasias docu-
mented by fundus photography and fluorescein angiography
was recorded. Type of treatment on initial visit and all subse-
quent examinations was recorded.
Outcomes measured were (1) number of treatment sessions
required, (2) time to full treatment (full treatment was defined
as complete ablation of telangiectasias and resolution of SRF)
and (3) percentage of eyes achieving complete resolution of
disease without the need for incisional surgery (ie, vitrectomy,
surgical drainage of SRF, scleral buckle). Resolution of disease
was defined as complete ablation of retinal telangiectasias and
reabsorption of all SRF.
The Institutional Review Board of Emory University School
of Medicine (Atlanta, Georgia, USA) approved the retrospective
review of this series.
RESULTS
Ten patients received intravitreal bevacizumab plus laser or cryo-
therapy for treatment of Coats’ disease from May 2009 to
October 2010. Twenty-six children diagnosed with Coats’
disease not treated with bevacizumab were identified. Each eye
treated with bevacizumab was matched in a blinded fashion
with a control eye based on baseline characteristics as outlined
above (see online supplementary figure S1).
Baseline characteristics of both groups are outlined in online
supplementary table S1. Matched pairs were given the same cor-
responding number in each study group. All patients had exten-
sive submacular exudation consistent with poor visual acuity
and most patients in both groups had exudative retinal
detachments. Severity based on the Shields classification ranged
from stage 2B to 3B in both groups (see online supplementary
table S1).23 Fluorescein angiography was performed on all sub-
jects at baseline and all had vascular abnormalities consistent
with the diagnosis of Coats’ disease. All patients had normal
ocular exams of the fellow eye except patient 9 in the bevacizu-
mab group which had minimal abnormal peripheral vasculature
seen on fluorescein angiography. The patient had no systemic
abnormalities, the parents had no known eye disease, and the
fellow eye did not require treatment during the study period.
There was a similar ratio of males to females in each study
group (9 : 1 and 8 : 2 in the bevacizumab and control groups
respectively).
There was no statistical difference between baseline character-
istics when comparing the bevacizumab group to the control
group including age and quadrants of telangiectasias (4.88 years
vs 4.64 years, p=0.86; 2.4 quadrants vs 2.2 quadrants, p=0.59
respectively, Student’s paired t-test). The difference between the
baseline quadrants of SRF in the bevacizumab and control
groups (mean 1.7 vs 1.2 quadrants respectively), approached
significance p=0.05, Student’s paired t-test).
Therapeutic intervention and follow-up details for the bevaci-
zumab group and the control group are provided in tables 1 and
2, respectively. Patients that received bevacizumab received
either 0.625 mg or 1.25 mg of drug at each treatment. The
lower dose of the drug was used in six injections in three
patients that were seen and treated at the beginning of the
change in practice pattern (May 2009). Injections in all cases
were given using a 30-gauge needle through the pars plana,
2.5–3.5 mm posterior to the limbus depending on the age of
the patient. Bevacizumab was only used in the first two to three
treatment sessions (average number received was 2.5). Patient’s
in both groups received laser photocoagulation and/or cryother-
apy to treat active telangiectasias. The number of treatment ses-
sions required differed significantly between the two groups
with the eyes treated with bevacizumab requiring more total
treatments (4.3 sessions vs 2.6 sessions, p=0.002, Student’s
t-test). The time to full treatment of active telangiectasias was

Table 1 Therapeutic interventions for bevacizumab group

Dose Dose Other Number of Time to full Fully treated Length of
Patient #Bevacizumab* 1.25 mg† 0.625 mg† therapy‡ treatment sessions treatment (months)§ disease¶ follow-up (months)

1 3 1 2 Laser×1 5 9.6 Yes 18.5

Cryo×5
2 3 1 2 Cryo×3 3 5.1 Yes 14.9
3 3 3 0 Cryo×5 6 12.6 Yes 19.6
4 2 1 1 Laser×2 6 12.8 Yes 16.3
Cryo×4
5 2 2 0 Laser×1 5 11.1 Yes 18.1
Cryo×3
6 2 2 0 Cryo×3 3 4.4 Yes 16.1
7 3 3 0 Laser×1 4 7.5 Yes 14.8
Cryo×3
8 3 3 0 Cryo×4 4 7.9 Yes 14.4
9 1 1 0 Laser×3 3 6.1 Yes 11.0
10 3 3 0 Cryo×4 4 7.9 Yes 10.3
Average 2.5 4.3 8.1 15.4
*Total number of intravitreal injections of bevacizumab received.
†Number each of individual doses of bevacizumab.
‡Number of other therapies received (laser photocoagulation (Laser) and/or cryotherapy (Cryo)).
§Patients 3 and 7 excluded from average/statistical analysis because matched controls did not reach full treatment.
¶Fully attached retina with no remaining active telangiectasias.

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Clinical science

Table 2 Therapeutic interventions for control group

Standard Salvage surgical Number of treatment Time to full treatment Length of follow-up
Patient therapy* therapy sessions (months)† Fully treated disease‡ (months)

1 Laser×1 n/a 2 2.5 Yes 19.2

Cryo×1
2 Laser×1 n/a 3 6.8 Yes 10.1
Cryo×3
3 Cryo×3 SRF drainage×1 2 n/a No—Enucleation 105.0
PPV/SO×2
4 Laser×1 n/a 3 5.8 Yes 15.2
Cryo×2
5 Cryo×3 n/a 3 7 Yes 25.0
6 Cryo×2 n/a 2 3.6 Yes 15.5
7 Laser×2 n/a 3 n/a No—NLP; total 138.9
Cryo×1 exudative RD
8 Cryo×3 n/a 3 6.1 Yes 11.7
9 Cryo×2 n/a 2 3.3 Yes 24.4
10 Cryo×3 n/a 3 6.1 Yes 31.6
Average 2.6 5.1 39.7
*Number of other therapies received (laser photocoagulation (Laser) and/or cryotherapy (Cryo)).
†Patients 3 and 7 excluded from average/statistical analysis because they did not reach full treatment.
‡Fully attached retina with no remaining active telangiectasias.
NLP, no light perception vision; PPV/SO, pars plana vitrectomy with silicone oil tamponade; RD, retinal detachment; SRF, subretinal fluid.

significantly longer for the bevacizumab group compared with
the standard therapy control group (8.1 months vs 5.1 months,
p=0.03, Student’s t-test).
Two patients were treated initially with bevacizumab alone.
The first had a total retinal detachment on presentation and
received bevacizumab 1.25 mg (bevacizumab group—case 3).
Minimal improvement was seen on follow-up 1 month later
(figure 1). The second patient to receive initial bevacizumab
monotherapy (bevacizumab group—case 5) did not show any
resolution of SRF or decrease in submacular exudate at 5-week
follow-up after a single injection (figure 2), but had subjective
and measurable improvement in visual acuity (1/200–20/400).
Two patients in the control group failed standard thermal
ablative therapy. One of these patients (control group—case 3)
underwent several surgeries in an attempt to salvage the eye, but
despite these interventions required enucleation for a blind,
painful eye. The other patient (control group—case 7) had per-
sistent retinal detachment and had no light perception in the
affected eye. The family deferred further surgical intervention.
The matched eyes from the bevacizumab group (cases number 3
and 7, bevacizumab group) had similar quadrants of telangiecta-
sias and SRF but were quiescent with fully treated telangiectasias
and resolved exudative retinal detachment at last follow-up.
Patient 7 in the bevacizumab group had marked reduction of
total exudative retinal detachment after two treatment sessions
that included bevacizumab plus laser and cryotherapy (figure 3).
During the follow-up (average 9 months) there were no
adverse events in the bevacizumab group. Intraocular pressure
remained normal in all patients and there were no cases of rheg-
matogenous retinal detachment or endophthalmitis. No systemic

Figure 1 Six-year-old boy with

Coats’ disease of the left eye
(bevacizumab group—case 3).
(A) Preinjection fundus photograph
showing total exudative detachment
with exudates extending into macula.
(B) Preinjection fluorescein
angiography showing peripheral
telangiectasias with leakage. (C) One
month postinjection fundus
photography showing slightly less
subretinal fluid. (D) One month
postinjection fluorescein angiography
showing slightly less engorgement of
telangiectatic vessels.

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Clinical science

Figure 2 Twelve-year-old boy with Coats’ disease of the right eye treated initially with bevacizumab only (bevacizumab group—case 5). (A)
Preinjection fundus photograph showing temporal exudative detachment/telangiectasias and submacular exudates. (B) Five weeks postintravitreal
bevacizumab 1.25 mg fundus photograph showing relatively unchanged exudative detachment and exudation.

events, including cardiovascular complications, were noted
during the follow-up.
DISCUSSION
The SRF and exudation seen in Coats’ disease can limit effective
thermal ablation of the incompetent vasculature. Current treat-
ments of this exudative detachment are suboptimal. Globe
salvage remains difficult in a significant number of cases. In a
series of Coats’ disease patients reported by Shields and associ-
ates, 16% of eyes required enucleation for end-stage disease.23
There have been several case reports describing intravitreal
bevacizumab as an effective adjuvant to traditional therapy for
Coats’ disease to decrease SRF. In our case-control series we
have found that combined bevacizumab plus laser and cryother-
apy did not reduce the time to full treatment or the number of
treatment sessions required. We did however successfully treat
even the most severe cases in the bevacizumab group whereas
matched control patients with similar severity of disease failed
therapy with laser and cryotherapy alone.
The matched case-control patients in our series had similar
baseline characteristics though the patients treated with bevaci-
zumab had slightly more SRF on presentation (mean 1.7 vs 1.2
quadrants of SRF for bevacizumab and control groups respect-
ively, p=0.05). This may have played a role in the bevacizumab
group requiring more time for complete treatment of disease
despite the use of intravitreal anti-VEGF. The difference in
number of treatment sessions required may be due to the close
follow-up and additional treatments received in the bevacizumab
group as early on they were seen 4–5 weeks after injection to
ensure no adverse events were taking place. Treatment sessions
before bevacizumab was available were typically spaced
3–4 months apart.
Two of our cases were treated initially with a single injection
of bevacizumab and minimal change was observed in the fundus
appearance 1 month later. This apparent lack of efficacy of a
single injection in Coats’ is in contradistinction to retinopathy
of prematurity, exudative macular degeneration and retinal vein
occlusion where a single injection often has a dramatic effect,
and may be dictated by the severity of tissue changes seen in
Coats’ disease. Others have reported resolution of macular
oedema in Coats’ with repeated injection of bevacizumab.10
Their case showed localised vascular anomalies and exudation
associated with macular oedema without the extensive SRF or
lipid deposition seen in our cases. Much in the same manner
that the standard dose of bevacizumab is effective for macular
disease such as choroidal neovascularisation, perhaps in non-
severe cases of Coats’ disease intravitreal anti-VEGF agents are
more effective in achieving resolution of leakage. In severe cases
like those in our series, the area of diseased tissue may be too
great for a single standard dose to show effect.
Analysis of ocular fluid concentration of VEGF in other
studies supports this hypothesis. Three studies that analysed
aqueous fluid from patients undergoing cataract extraction (no
retinal disease) revealed average VEGF levels of 51.2, 81.8 and
102.7 pg/ml respectively.24–26 Patients with choroidal neovascu-
lar membranes secondary to age-related macular degeneration
had average aqueous levels of VEGF around 67 pg/ml in the
same studies.24 25 Others have shown that average aqueous
levels of VEGF in patients with branch vein occlusions are less
than 500 pg/ml.27 In contrast, patients with Coats’ disease have
been shown to have aqueous and vitreous levels of VEGF
around 1000 pg/ml.4 5 Though these studies show a decrease in
aqueous levels of VEGF after use of anti-VEGF agents, it is pos-
sible a significant effect in reduction of SRF is not possible with

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Clinical science

Figure 3 Four-year-old boy with Coats’ disease of the right eye (bevacizumab group—case 7). (A) Fundus photo of the right eye on presentation
showing total exudative detachment with retinal macrocyst and subretinal exudates. (B) Fundus fluorescein angiography of the right eye on initial
presentation showing extensive telangiectasias. (C) Therapy included bevacizumab 1.25 mg and cryotherapy at initial presentation followed by
bevacizumab 1.25 mg and laser photocoagulation of telangiectasias 6 weeks later. Fundus photo of the right eye after the two described treatment
sessions (4 months after initial presentation) showing markedly reduced subretinal fluid and coalescence of subretinal exudation. (D) Fundus photo
of the right eye 7 months after presentation (three treatment sessions including three intravitreal bevacizumab). The eye received cryotherapy to
residual telangiectasias at this visit and remained attached with no residual active telangiectasias during the follow-up period (14.8 months).

the standard dose or with only a single injection. In retinopathy
of prematurity, vitreous VEGF levels average 3454 pg/ml (range
774–8882 pg/ml)28 and recent studies reveal that a single dose
of intravitreal bevacizumab is efficacious in decreasing the
abnormal vascular activity in that disease process.29 It is possible
that other cytokines not involved in the pathophysiology of ret-
inopathy of prematurity play a role in Coats’ disease. In add-
ition, the chronic nature of the exudation and associated tissue
changes seen in Coats’ disease may make it less amenable to
anti-VEGF therapy than retinopathy of prematurity.
It is possible that repeated injections of bevacizumab may be
effective at reducing SRF in severe Coats’ disease. A study by
Lin et al12 supports this idea. They prospectively treated two
patients who had extensive SRF and exudation with three con-
secutive injections of bevacizumab. Both cases had substantial
reduction in SRF, which allowed improved treatment with
standard thermal ablative therapy. Our cases also showed reso-
lution of fluid and decreased exudation after repeated injections
of bevacizumab, however our patients were concurrently receiv-
ing standard therapy. This makes it difficult to draw conclusions
about the efficacy of repeated bevacizumab injections alone
during these time points. It is possible, however, in patients
with a significant amount of telangiectasias, and therefore, large
areas of incompetent vasculature require several treatments with
intravitreal anti-VEGF before an effect is realised (figure 3).
The findings of this study differ from our experience treating
Coats’ disease with IVTA.2 Though rapid resorption of SRF was
seen after treatment with IVTA this was not noted after intravi-
treal bevacizumab. Bevacizumab treated eyes also did not
develop the fibrosis and vitreous contraction that lead to the
high rate of proliferative vitreoretinopathy and rhegmatogenous
retinal detachment associated with IVTA. Vitreoretinal fibrosis
and tractional retinal detachment was seen, however, in 50% of
eyes (four of eight) in a recent series of children who underwent
combined intravitreal bevacizumab plus thermal ablative therapy
for Coats’ disease.21 The severity of disease, length of follow-up
and treatment regimen was similar to our group of patients and
it is unclear why our patients did not have a similar response.
This is the largest case series evaluating the use of intravitreal
bevacizumab for Coats’ disease in a paediatric population.
Though limited by retrospective design and small number of
patients, the results suggest a benefit from bevacizumab in the
severest cases of Coats’ disease. Bevacizumab does not appear to
reduce the time to full treatment or number of treatment ses-
sions. Though no adverse events occurred in our series, this
study was not designed to evaluate the safety of intravitreal bev-
acizumab in this population.
Based on our series and a review of the literature, intravitreal
bevacizumab may play a role as adjuvant therapy in select cases
of severe Coats’ disease. The results of intravitreal bevacizumab
are not as dramatically beneficial in Coats’ disease as they are
for other retinal diseases like age-related macular degeneration
or retinal vein occlusion. A series of injections, especially in
severe cases, in an attempt to reduce the amount of SRF to
allow more effective ablative procedures is a reasonable proto-
col. A caveat to this recommendation is that the diagnosis must
be certain before delivery of an intraocular medication.
Retinoblastoma can easily mimic severe Coats’ disease and

276 Ray R, et al. Br J Ophthalmol 2013;97:272–277. doi:10.1136/bjophthalmol-2012-302250

 Downloaded from bjo.bmj.com on July 16, 2014 - Published by group.bmj.com
violation of sclera into a tumour filled eye could prove
catastrophic.30
Contributors RR, who serves as first author, cooperated in study design,
performed necessary literature review, collected data, performed the statistical
analysis, analysed the data, and drafted and revised the paper. DEB, who serves as
coauthor collaborated on study design, helped collect and analyse data, and revised
the paper. GBH, who serves as corresponding author, initiated the study concept,
participated in literature review and revised the paper.
Funding Supported in part by an unrestricted grant from Research to Prevent
Blindness, Inc., New York, New York. The funding organisation had no role in the
design or conduct of this research.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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Treatment of Coats' disease with intravitreal

bevacizumab
Robin Ray, David E Barañano and G Baker Hubbard

Br J Ophthalmol 2013 97: 272-277 originally published online

December 25, 2012
doi: 10.1136/bjophthalmol-2012-302250

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