COVER STORY

Anti-VEGF as
Adjunctive Therapy
for Coats Disease
In this case report, anti-VEGF therapy obviated the need
for subretinal drainage, improving outcomes.
BY KARL WAITE, MD; EUGENE NG, MD, MBA; AND MICHAEL D. BENNETT, MD

oats disease is an idiopathic exudative

C retinopathy characterized by abnormal

retinal vascular development (telangiectasia)
that results in massive intraretinal and subreti-
nal lipid accumulation. This disease entity was first
described by a Scottish ophthalmologist, George Coats,
The clinical picture of Coats
disease is that of localized,
lipid-rich, subretinal exudation
in 1908.1 Coats disease is classically a unilateral process and abnormal vasculature.
(80% of cases) affecting young males with a peak age of
diagnosis at 6 to 8 years of age, without racial predomi-
nance. Males are affected three times as often as females. In 1971, Tripathi and Ashton4 described in detail the
An adult variant of the disease is less commonly seen and pathologic features of Coats disease, comprised of a
is frequently associated with hypercholesterolemia. host of retinal abnormalities, in particular the absence
of endothelium and pericytes in aberrant retinal blood
PATHOPHYSIOLOGY OF COATS DI SE A SE vessels. They proposed presciently that abnormal
The clinical picture of Coats disease is that of localized, endothelial permeability, ie, breakdown of the inner
lipid-rich, subretinal exudation and abnormal vasculature, blood-retinal barrier, was the primary pathology.
including aneurysmal dilitations, telangiectasias, areas of Whether this breakdown was structural or functional, it
capillary nonperfusion, and neovascularization. Shields et would secondarily result in telangiectasis and leakage.
al2 defined the stages of Coats disease as following Stage 1 Three decades later, Black et al,5 through genetic analy-
is limited to retinal telangiectasia. Stage 2 includes telang- sis, proposed that a somatic mutation in the NDP gene,
iectasia with exudation (2A is extrafoveal and 2B is foveal which results in a deficiency of the protein norrin, is a
exudation). Stage 3 occurs with development of an causal factor in Coats disease. The NDP gene is respon-
exudative retinal detachment (3A subtotal and 3B total sible for Norrie disease, and researchers believe that
retinal detachment). Stage 4 has total retinal detachment norrin is important in normal retinal vasculogenesis.
with glaucoma, and Stage 5 is advanced, end-stage dis-
ease. The natural history of Coats disease is generally pro- TRE ATMENT OF COATS DI SE A SE
gressive, but in a variably relapsing-remitting fashion. Early therapeutic intervention is necessary to halt the
Spontaneous remissions have rarely been reported.3 progression of Coats disease. Laser photocoagulation or

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Figure 1. Subretinal exudation extending into the fovea. Figure 2. Subretinal exudation inferior to the macula.

Figure 3. Fluorescein angiography of the right eye shows Figure 4. Fluorescein angiography of the left eye shows simi-
abnormal inferotemporal vessels with aneurysmal dilatation lar changes as in Figure 3, but less severe.
and telangiectasia with profuse leakage.

Figure 5. Photo of the right eye 7 months after treatment. Figure 6. Photo of the left eye 7 months after treatment.
The patient’s vision improved to 20/20 in both eyes.

cryotherapy are traditionally employed to destroy abnor- drainage, and vitreous replacement with air, gas, or silicone
mal retinal vessels in the early stages of the disease. More oil for retinal reattachment. These traditional approaches,
advanced stages typically require surgical interventions, however, in particular cryoablation, can incite further
such as vitrectomy, scleral buckling, subretinal fluid inflammation and breakdown of the blood-retinal barrier,

APRIL 2010 I RETINA TODAY I 47

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Figure 7. Fluorescein angiography of the right eye 5 months Figure 8. Fluorescein angiography of the left eye 5 months
after treatment demonstrated obliteration of abnormal ves- after treatment.
sels with cessation of peripheral leakage in both eyes.

which compromise the visual outcome. Recently, anti- agulation only, as the amount of subretinal exudation did
vascular endothelial growth factor (anti-VEGF) agents not necessitate treatment with intravitreal bevacizumab.
(bevacizumab [Avastin, Genentech, Inc.], ranibizumab Seven months after treatment, the patient regained
[Lucentis, Genentech, Inc.], and pegaptanib sodium vision to 20/20 in both eyes (Figures 5 and 6).
[Macugen, Eyetech]) have been used adjunctively. Fluorescein angiography 5 months after treatment
Intraocular corticosteroids have also been employed. demonstrated obliteration of abnormal vessels with ces-
Multiple case reports and case series document bene- sation of peripheral leakage in both eyes (Figures 7 and
ficial responses to anti-VEGF agents in Coats’ disease.6-13 8). The peripheral retina completely flattened in both
Intraocular VEGF is noted to be elevated in Coats dis- eyes and now has an epiretinal membrane that devel-
ease.13 Typically, anti-VEGF agents are used to stabilize oped over the course of treatment in the right eye.
the blood-retina barrier and reduce the amount of sub-
retinal exudation prior to laser photocoagulation. These DISCUSSI ON
reports often document substantial improvement of Given the rarity of Coats disease and its variable
visual acuity, rather than mere stabilization of the dis- course, therapeutic strategies have to be tailored to each
ease process or preservation of the globe, as is expected individual patient. As with other diseases, a search for
with more traditional approaches. approaches that improve outcomes with fewer side
effects is warranted. A promising new addition to our
CA SE REPORT retinal tool kit is perioperative intravitreal anti-VEGF
One exemplary case from our institution is that of a agents. With reduction of vascular permeability, there
15 year-old boy who presented with bilateral Coats dis- have been reports of reduction in subretinal lipid exuda-
ease. The patient presented with decreased visual acuity tion, exudative retinal detachment, and macular edema
(20/50) in his right eye secondary to subretinal exudation in patients with Coats. This enables more effective laser
extending into the fovea (Figure 1) and peripheral visual photocoagulation, as the retina is better apposed to the
field changes in his left eye (visual acuity 20/20) second- retinal pigment epithelium following anti-VEGF treat-
ary to subretinal exudation inferior to the macula (Figure ment. In our case, we believe that the use of intravitreal
2). Fluorescein angiography of the right eye (Figure 3) bevacizumab obviated the need for subretinal fluid
revealed abnormal inferotemporal vessels with aneurys- drainage, and we support its use as an adjunct prior to
mal dilatation and telangiectasia, which leaked profusely. laser photocoagulation. The promising efficacy signals
Peripheral to the abnormal vasculature was an area of observed with anti-VEGF agents suggest that VEGF
capillary nonperfusion. Fluorescein angiography of the plays a role in the pathophysiology of Coats disease.
left eye (Figure 4) demonstrated similar vascular Areas of retinal ischemia are present in the disease, and
changes, but of less severity. The patient was treated anti-VEGF therapies presumably act by reducing vascu-
with intravitreal bevacizumab and laser photocoagula- lar permeability secondary to VEGF blockade.
tion, followed by vitrectomy with fluid-air exchange in In summary, a multimodality and stepwise approach
his right eye. His left eye was treated with laser photoco- to the treatment of Coats disease, including the use of

48 I RETINA TODAY I APRIL 2010

 COVER STORY

tools that target the pathophysiology of the disease, angiogenesis. Hum Mol Genet. 1999;8(1):2031-2035.
6. Chiu SL, Chen SN, Chen YT, Chen PJ. Coats’ Disease and neovascular glaucoma in a
appears to provide encouraging results. ■ child with neurofibromatosis. J Pediatr Ophthalmol Strabismus. 2010 Feb 26:1-3. [Epub
ahead of print]
7. Entezari M, Ramezani A, Safavizadeh L, Bassirnia N. Resolution of macular edema in
Karl Waite, MD, is a vitreoretinal fellow at the Coats’ disease with intravitreal bevacizumab. Indian J Ophthalmol. 2010;58(1):80-82.
8. Kaul S, Uparkar M, Mody K, Walinjkar J, Kothari M, Natarajan S. Intravitreal anti-vascular
Retina Institute of Hawaii in Honolulu. endothelial growth factor agents as an adjunct in the management of Coats’ disease in chil-
Eugene Ng, MD, MBA, is a vitreoretinal sur- dren. Indian J Ophthalmol. 2010;58(1):76-78.
9. Lin CJ, Hwang JF, Chen YT, Chen SN. The effect of intravitreal bevacizumab in the treat-
geon at the Retina Institute of Hawaii. ment of Coats disease in children. Retina. 2009 Dec 4. [Epub ahead of print]
Michael D. Bennett, MD, is a vitreoretinal sur- 10. Lin KL, Hirose T, Kroll AJ, Lou PL, Ryan EA. Prospects for treatment of pediatric vitreo-
retinal diseases with vascular endothelial growth factor inhibition. Semin Ophthalmol.
geon at the Retina Institute of Hawaii and an 2009;24(2):70-76. Review.
Associate Professor in the Department of Surgery 11. Jun JH, Kim YC, Kim KS. Resolution of severe macular edema in adult Coats’ disease
with intravitreal triamcinolone and bevacizumab injection. Korean J Ophthalmol.
at the University of Hawaii, John A. Burns School 2008;22(3):190-193.
of Medicine. He states that he is a paid consult- 12. Cakir M, Cekiç O, Yilmaz OF. Combined intravitreal bevacizumab and triamcinolone
injection in a child with Coats disease. J AAPOS. 2008;12(3):309-311.
ant to Alcon Laboratories, Inc., Allergan, Inc., 13. Sun Y, Jain A, Moshfeghi DM. Elevated vascular endothelial growth factor levels in Coats
Genentech, Inc., Optimedica, Optos, Optovue, disease: rapid response to pegaptanib sodium. Graefes Arch Clin Exp Ophthalmol.
2007;245(9):1387-1388.
(OSI) Eyetech, Heidelberg Engineering, and
Neovista. Dr. Bennett is a Retina Today Editorial
SHARE YOUR FEEDBACK
Board member. He can be reached at +1 808 955
0255. Would you like to comment on an author’s article?
1. Coats G. Forms of retinal disease with massive exudation. Royal London Ophthalmic
Do you have an article topic to suggest?
Hospital Reports.1908;17(3):440-525. Do you wish to tell us how valuable
2. Shields JA, Shields CL, Honavar SG, Demirci H, Cater J. Classification and management
of Coats disease: the 2000 Proctor Lecture. Am J Ophthalmol. 2001;131:572-583. Retina Today is to your practice?
3. Jones JH, Kroll AJ, Lou PL, Ryan EA. Coats’ disease. Int Ophthalmol Clin.
2001;41(4):189-198. We would like to hear from you. Please e-mail us at
4. Tripathi R, Ashton N. Electron microscopical study of Coat’s disease. Br J Ophthalmol.
1971;55(5):289-301. [email protected] with any thoughts or
5. Black GC, Perveen R, Bonshek R, et al. Coats disease of the retina (unilateral retinal questions you have regarding this publication.
telangiectasis) caused by somatic mutation in the NDP gene: a role for norrin in retinal

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