Download Concurrent Corticosteroid and bevacizumab (Avastin) Treatment of

Yao Lu
Concurrent Corticosteroid and Bevacizumab (Avastin) Treatment of
Sarcoid Choroidal Granuloma
Abstract:
A solitary choroidal mass is found in a 52 year-old black female. A kidney biopsy
confirms sarcoidosis as the etiology. Systemic steroids and intravitreal bevacizumab injections
resolve the granuloma and improve visual acuity.
Case Report:
A 52-year-old black woman presented with an 8-week history of blurred vision in her left
eye. She reported no other ocular complaints. Her past ocular and medical histories were noncontributory, and she was taking no medications. Her family history was unremarkable.
Ocular examination showed best-corrected visual acuities of 20/20 in the right eye and
20/200 in the left eye. External examination was normal. Pupils were isocoric without an
afferent defect. Intraocular pressures measured 15mmHg OU. Anterior segment examinations
were unremarkable bilaterally. Dilated fundus examination of the right eye was unremarkable.
Fundus examination of the left eye revealed an elevated, relatively amelanotic mass adjacent to
the macula with minimal focal intrinsic pigment. A choroidal neovascular membrane was
observed overlying the surface of the lesion. The vitreous was clear, with no cells or opacities.
The optic nerves were perfused and well-defined OU. The retinal vessels were normal, with no
associated hemorrhages or exudates. Peripheral examination revealed intact grounds.
Ancillary testing included b-scan ultrasound, fluorescein angiography and optical
coherence tomography (OCT). Ultrasound examination of the left eye confirmed the choroidal
mass. The mass showed medium internal reflectivity and measured 8.5 x 6.5 x 1.3 mm.
Intravenous fluorescein angiography revealed early hypofluorescence of the mass, with late
hyperfluorescence and diffuse leakage into the subretinal space. OCT showed retinal pigment
epithelial thickening with surrounding subretinal fluid.
A detailed systemic evaluation was performed to aid in the diagnosis. A CT of the chest,
abdomen, and pelvis with contrast showed evidence of pulmonary and renal infiltrative
processes. At this point, given the pulmonary and renal findings, lymphoma was of concern.
Subsequently, a CT-guided kidney biopsy was performed. Pathology reports showed noncaseating granulomas, which led to the diagnosis of multisystem sarcoidosis. Initially, the
patient had only ocular symptoms. However, during the course of the investigations, the patient
became symptomatic, manifesting dyspnea on mild exertion.
The differential diagnosis of a solitary choroidal mass in the absence of any other
intraocular sequelae includes inactive inflammatory lesion, amelanotic melanoma of the choroid,
solitary choroidal hemangioma, choroidal metastasis, and osseous choristoma.1 Along with
sarcoidosis other possible causes of granulomatous inflammation of the choroid include
infectious diseases such as tuberculosis, syphilis, toxocarasis and noninfectious diseases such as
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sympathetic ophthalmia and Vogt-Koyanagi-Harada syndrome.1 Idiopathic polypoidal choroidal
vasculopathy also needs to be included in the list of differentials.2 With regards to the
neovascular membrane, it was believed that it was secondary to the amelanotic lesion, and as any
disruption in the integrity of the choroid/RPE/retinal interface can lead to neovasculariztion
differentials were limited to the mass itself.3 The leading differentials were amelanotic
melanoma and sarcoidosis.
Discussion:
Sarcoidosis is a chronic multisystem granulomatous disorder characterized by
noncaseating granulomas thought to result from an exaggerated cellular immune response to a
variety of self and non-self antigens.4 In the United States, cases of sarcoidosis occur more
frequently in black women over the age of 40.5 The most common organ involvements are in the
lung, skin, eye, lymph nodes, liver and spleen.6 Diagnosis of sarcoidosis can be difficult as the
exact etiology remains elusive.5,6 If sarcoidosis is suspected, investigations should include a
chest x-ray, ACE and possible gallium scan.4 A biopsy of granulomas when possible can
provide a definitive diagnosis. However, in cases with suspicious granulomas, malignancy and
infectious processes must be ruled out first.6 Symptomatic sarcoidosis is typically managed with
glucocorticoids or other immunosuppresants. 7
Ocularly, sarcoidosis can manifest itself in multiple ways.4 These include, external lid
lesions, lacrimal gland enlargement, conjunctival granulomas, anterior, posterior and
intermediate uveitis, periphlebitis, choroidal granuloma and optic nerve infiltration. 5 This case
included a solitary choroidal granuloma without corroborating evidence of active inflammation.
This is consistent with sarcoid granulomas which are typically described as being yellow-gray in
color with or without overlying vitritis or vasculitis.1 Ocular manifestations are seen in
approximately 22% of saroidosis cases.8 85% of these cases have anterior segment
inflammations with approximately 25% involving the posterior segment.8 Posterior segment
disease without anterior segment involvement is unusual, occurring in only 5% of patients with
ocular sarcoidosis, and among them, only 12% may present with choroidal granuloma.1,8
Without a previous systemic diagnosis, choroidal sarcoidosis is likely to be confused with
other diseases.9 Choroidal metastaic carcinoma can also produce pale yellow macular and
paramacular choroidal infiltrates with frequent subretinal fluid extension to the fovea.9
Lymphoma can occasionally manifest isolated choroidal involvement without vitritis or central
nervous system findings and maybe confused with sarcoid choroidal infiltration.9 Hence, Campo
and Aagerg believe that biopsy confirmation is needed in these cases because noninvasive tests
such as gallium scans and angiotensin-converting enzyme cannot be relied upon for diagnosing
sarcoidosis and excluding carcinoma.9 In this particular case, the final diagnosis was made based
on the kidney biopsy showing non-caseating granulomas.
Treatment:
The patient was treated with systemic prednisolone by her pulmonologist. Oral
corticosteroid therapy has long been used for inflammatory diseases involving the posterior
segment despite their possible ocular side effects.8 Multiple cases of sarcoidosis related
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choroidal granulomas have been treated successfully with oral corticosteroids alone.1, 2, 9, 10 Chan
et.al. reported using intravitreal triamcinolone acetonide for choroidal granuloma in sarcoidosis
that was refractory to systemic prednisolone.8 After three injections at 2-month intervals, a slow
but substantial regression in the size of the granuloma was observed.8 Best corrected visual
acuity quickly improved and stabilized at 20/40. 8
Complicating this case was the presence of the concurrent choroidal neovascular
membrane. It is well established that clinical entities that affect the choroid and RPE, leading to
changes in Bruch’s membrane can lead to neovascularization.3 An imbalance occurs between
angiogenic molecules and inhibitor molecules leading to capillary endothelial cell proliferation
and migration.3
Recent developments in this molecular understanding of ocular
neovascularization have led to the advent of anti-VEGF ocular therapies.11 Bevacizumab
(Avastin), a monoclonal antibody to VEGF, was originally used in cases of neovascularization
related to AMD.11 Since these initial studies on AMD, the use of Avastin has expanded to
include numerous other clinical entities.11
Our patient underwent a series of seven intravitreal Avastin injections in the left eye over
a period of 26 months. Follow up examinations revealed an involutional response of the
choroidal neovascular membrane with subsequent chorioretinal scarring. Best-corrected acuity
improved steadily and stabilized at 20/25. The condition remained stable as of the last follow up
in August 2009.
A recent review of the literature shows that there are currently no reported cases of
sardoidosis related choroidal neovascular membranes treated with Avastin. However, given the
clinical success in this case and in multiple other cases with different etiologies, this treatment
method is becoming a well-established off-label management.
Conclusion:
Although rare, choroidal granuloma can be the sole ocular manifestation of sarcoidosis.
Complete medical evaluation including appropriate laboratory and serological tests and most
importantly, a tissue biopsy are crucial to the diagnosis and management of this case. Off-label
use of Avastin for an associated choroidal neovascular membrane in conjunction with systemic
corticosteroid therapy resulted in the complete resolution of the lesion with significant
improvement of visual acuity.
References
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