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Choroidal sarcoid granuloma: a case report and review of the literature
Journal of Ophthalmic Inflammation and Infection volume 12, Article number: 31 (2022)
Choroidal sarcoid granulomas are often diagnosed in patients without a prior history of sarcoidosis. They are often mistaken for choroidal metastasis, choroidal nevi, amelanotic choroidal melanomas, and uveal lymphomas; however, are easily treatable when accurately identified.
We searched PubMed, Medline, and Scopus for English-Language case reports published before September 2021. Additionally, we presented a case of a 45-year-old woman with a right-sided amelanotic choroidal mass whose diagnosis was delayed by a COVID-19 infection. Of the 26 cases reported in the literature, 46% were female, 38% were African American, and 19% had bilateral involvement. There was a mean age of 42.15 years and a mean follow-up period of 27 months. The most common complaint was of a progressive, painless blurring of vision, and only five patients had been previously diagnosed with sarcoidosis. The choroidal granulomas were typically described as yellow lesions, single or multiple, found temporal to or at the macula. Most patients were administered steroids, with 69% receiving them systemically, 5% topically, and 8% locally with a triamcinolone injection. All patients reported symptomatic improvement at their final follow-up with resolution of the mass in 65% of patients and improved visual acuity in 76%.
Primary testing including fundoscopy, fluorescein angiography, fundus autofluorescence, A/B-scan, and OCT are useful for diagnosis, differentiation from other choroidal lesions, and monitoring treatment response. Steroids are a mainstay of treatment for sarcoidosis and are effective at treating choroidal granulomas. Therefore, early recognition and diagnosis of choroidal granulomas is imperative as treatment can be curative and sight-sparing.
Sarcoidosis is a chronic inflammatory granulomatous disease that can affect multiple major organ systems including the eye and its surrounding structures . The wide variability of clinical manifestations has posed diagnostic challenges that make it difficult to ascertain the true prevalence of the disease . It is currently estimated that 13–79% of those affected by sarcoidosis will develop ocular manifestations [2,3,4,5]. Ocular symptoms are often the initial notable finding in 20–30% of cases, with uveitis (30–70%) and conjunctival nodules (40%) being the most encountered [3, 6, 7]. Additionally, studies by Rothova et al. and Evan et al. demonstrated that females (56% versus 23%) and African Americans are more likely to develop ocular involvement [2, 7, 8].
Uveitis is an inflammatory process that affects the uveal tissues - iris, ciliary body, choroid – and surrounding structures – anterior chamber, retina, vitreous humor . It is often identified on slit lamp or fundus examination and classified as anterior, intermediate, posterior, or panuveitis . When associated with sarcoidosis, uveitis can be further categorized based on the presence of granulomatous inflammation, and a study of 112 eyes by Dana et al. noted a prevalence of granulomatous inflammation in 81% of those with sarcoid uveitis [2, 9]. Choroidal inflammation can lead to the development of choroidal granulomas and symptoms differ based on the location of the lesion (central versus peripheral) . Furthermore, the granulomas may vary in size and be unifocal or multifocal [2, 10, 11]. They can also lead to choroidal neovascularization and exudative retinal detachments [2, 12].
This article summarizes all published case reports documenting choroidal sarcoid granulomas in the English language from December 1982 to July 2021 and presents a unique case of a choroidal granuloma in a patient with previously undiagnosed sarcoidosis that was initially mistaken for malignancy.
A literature review accessing PubMed, Medline, and Scopus databases was performed in September 2021. The keywords “choroid,” “sarcoid,” “sarcoidosis” and “granuloma” were used to gather all peer-reviewed case reports published in the literature. Non-English case reports were excluded from the review. We used the PRISMA and CARE checklists when writing our report [13, 14].
A 45-year-old previously healthy female presented to the Ophthalmology Specialty Clinics at the American University of Beirut Medical Center with a referral diagnosis of a suspicious choroidal lesion associated with subretinal fluid in the right eye. The patient had no personal or family history of cancer. The patient was a current everyday hubble-bubble smoker but did not consume alcohol or use recreational drugs.
Best-corrected visual acuity was 20/25 in the right eye and 20/20 in the left eye. The anterior segment slit-lamp examination was unremarkable except for trace nuclear sclerosis in the right eye. Funduscopic examination demonstrated a quiet, acellular vitreous in both eyes with a yellow elevated choroidal lesion infra-temporal to the fovea of the right eye with a 2 × 3 mm basal diameter and overlying subretinal fluid (Fig. 1A). B-scan ultrasonography showed a dome-shaped, regularly structured, hyperechoic lesion of the choroid. The maximal thickness measured 2.18 mm, and no distinct extrascleral extension was noted (Fig. 2). Fundus autofluorescence (AF) of the right eye showed hyperautoflourescence with hypoautoflourescent stippling at the lesion (Fig. 3A). Fluorescein angiography (FA) showed normal retinal vasculature and a late diffuse staining of the entire lesion (Fig. 3B), whereas the indocyanine green angiography (ICG) showed an early hypocyanescence of the lesion that persisted into late into angiography (Fig. 3C). On optical coherence tomography (OCT) there was a right choroidal elevation with associated subretinal hyperreflective material and subretinal fluid (Fig. 3D).
Our differential diagnosis included amelanotic choroidal nevus/melanoma, hemangioma, uveal lymphoma, metastasis, and masqueraders. Given the results of the ophthalmic imaging, we were most suspicious of uveal lymphoma, metastasis, or a granulomatous process.
The patient was sent for complete oncologic screening examinations including mammography, chest, abdomen, and pelvis computerized tomography (CT) scan, and brain and orbit magnetic resonance imaging (MRI). All were non-revealing with no evidence of malignancy except for the chest CT scan showing few scattered subcentimetric lymph nodes in prevascular and bilateral hilar spaces. The decision was made for close follow-up considering the difficulty, low yield potential and vision threatening risk of a biopsy of the lesion. After an increase in subretinal fluid (SRF) and slight increase in diameter was noted on the 3-month follow-up (Fig. 1B), an oncologist was consulted. The recommended positron emission tomography (PET) scan showed concerning fluorodeoxyglucose (FDG) avid thoracic, abdominal, and pelvic lymphadenopathy. One day after the scan, the patient developed fever and upper respiratory tract symptoms and tested positive for COVID-19. Biopsy of the lymph nodes was deferred as oncology suspected the viral infection may have been the cause of her lymphadenopathy.
A repeat PET-CT scan at 3 months showed persistent lymphadenopathy. Clinically, the patient’s vision had worsened to 20/200 and the choroidal lesion had continued to increase in size with a largest basal diameter of 6.81 mm and a maximal thickness of 3.01 mm. An endobronchial ultrasound guided biopsy revealed a non-necrotizing granuloma suggestive of sarcoidosis. Systemic steroid therapy was initiated resulting in an improvement in vision to 20/60 and complete regression of the choroidal lesion with residual chorioretinal atrophy (Fig. 4).
Review of the literature
A summary of the 26 published cases of sarcoid granulomas is presented in Table 1. Regarding patient demographics, 46% of patients were female (12/26), and the mean age at diagnosis was 42.15 (range: 10–67). There was only one pediatric patient among the cases who was 10 years old at the time of diagnosis . Of the 26 cases, 16 reported racial demographics with 38% of patients being African American (6/16) [17, 20, 23, 34, 36], 38% Caucasian (6/16) [21, 24, 28, 32, 35, 36], and 25% Asian (4/16) [26, 27, 29, 33]. Among the 26 patients, 30 total eyes were affected, with 19% of patients having bilateral involvement (5/26) [16, 18, 25, 32], and the majority having unilateral involvement [42% right eye (11/26) [15, 17, 20,21,22, 24, 26, 31, 34, 36], 38% left eye (10/26) [18, 19, 23, 27,28,29,30, 33, 35]]. The mean follow-up period was 27 months (median: 12, range: 1–216). The most common visual complaint was a progressive painless blurring of vision (21/26) [15, 17, 18, 20, 21, 23,24,25,26, 28, 29, 31,32,33,34]. Other presentations included floaters (4/26) [15, 18, 20], eye pain (2/26) [23, 32], headaches (2/26) [17, 32], and those that were asymptomatic (5/26) [16, 19, 22, 27, 30].
Past medical history
Five patients had been diagnosed with sarcoidosis before developing choroidal granulomas [17, 19, 20, 27, 34], one patient had a history of psoriatic arthritis with sacroiliitis , two patients had a prior diagnosis of bilateral granulomatosis panuveitis [23, 26], and one patient had been diagnosed with bilateral granulomatous iritis 2.5 years prior to the development of the choroidal granuloma [26, 36]. Interferon-alpha (INF-a) use was found in 3 patients (2 female, 1 male) that were undergoing treatment for chronic Hepatitis C . Two men reported a prior history of prostate cancer, one treated with radiation therapy  and the other with radical prostatectomy . Two patients (1 female, 1 male) had a prior history of melanoma, with one patient undergoing Nivolumab therapy for metastasis  and the other having 5 prior excisions for dermal melanoma .
Examination findings and imaging
A summary of all the examination and imaging findings of the 26 cases is presented in Table 2. Fundoscopy was used in all 26 of the cases reviewed. Of the 26, there were single granulomas in 54% (14/26) [15, 17, 19, 21,22,23,24, 27,28,29, 31, 35, 36] and multiple in 46% (12/26) [16, 18, 20, 25, 26, 30, 32,33,34, 36]. Most lesions were yellow (13/26) [16, 17, 19,20,21, 23, 25, 26, 32, 35, 36] and located at, or temporal to the macula (9/26) [17, 21, 23, 27, 29, 31, 35, 36]. Some lesions were described as elevated (9/26) [15, 17, 21, 23, 32, 34,35,36], polypoid (1/26) , round (1/26) , white (3/26) [18, 27, 29], and creamy (3/26) [16, 30, 34]. Other notable locations include the posterior segment (4/26) [20, 22, 32, 34], optic disc (2/26) [28, 30], fundus (4/26) [18, 19, 25], fovea (1/26) , and arcade (3/26) [15, 16, 26]. Additionally, retinal detachments (6/26) [17, 20, 28, 36] and a choroidal detachment (1/26)  were observed.
Fluorescein angiography (FA) was used in 12 cases (46%) and demonstrated hyperfluorescence in 5 cases [15, 20, 23, 28, 36], early phase hypofluorescence with late-phase hyperfluorescence in 4 cases [23, 32, 35, 36], hypofluorescence in 2 cases [17, 27], punctate leakages in 1 case , subretinal leakages in 2 cases [33, 35] and periphlebitis in 1 case .
Fundus autofluorescence (AF) was used in 2 cases (8%) and showed hypoautofluorescence in areas of hemorrhage , speckled hypoautofluorescence overlying the lesion , and hypofluorescence and disc leakage near sites of the lesions .
Ultrasonography (A/B scan) was used in 9 cases (35%) and identified the presence of elevation in 4 cases [15, 28, 35, 36] and high internal reflectivity in 2 cases [29, 35], as well as the absence of elevation in 2 cases [16, 22] and the presence of calcification in 1 case . It also noted subretinal fluid in 1 case , a retinal detachment in another .
Ocular coherence tomography (OCT) was used in 10 (38%) cases and was notable for a homogenous hyporeflective lesion in 1 case , a homogenous hyperreflective lesion in 3 cases with thinning of the overlying choroidal architecture in 2 of those cases [21, 26, 34], subretinal fluid in 8 cases [19,20,21, 23, 26, 27, 31, 34], an exudative retinal detachment in 1 case , intraretinal cysts in 1 case , optic disc edema in 1 case , and a dome-shaped elevation of the choroid with effacement of the vessels in 1 case .
Indocyanine green (ICG) was used in 3 cases (12%) and showed hypocyanescence through the late phase of the angiogram in 1 case , low hypercyanescence with a filling delay in the area corresponding to the mass in 1 case , and low hypocyanescence with disc leakage in the last case .
Additional systemic investigations revealed lymphadenopathy on imaging in 54% of cases (14/26) [15,16,17,18, 21, 23, 24, 28, 29, 33,34,35,36], elevated ACE levels in 38% of cases (10/26) [15, 18, 26, 28, 30,31,32, 35, 36], and noncaseating granulomas on biopsy in 69% of cases (18/26) [17, 22,23,24,25,26,27,28, 30, 32,33,34,35,36]. Of the 18 cases that collected a biopsy, 61% (11/18) were from lymph nodes [17, 22, 24, 27,28,29, 33, 35, 36], 28% (5/18) from skin [26, 27, 30, 32, 34], 6% (1/18) from the choroid , 11% (2/18) were bronchial [23, 27], and 6% (1/18) did not specify the location .
Treatment and outcomes
Of the 26 cases, 18 (69%) received systemic steroids [15, 17,18,19,20,21, 23,24,25,26, 28, 29, 32,33,34,35,36], 5 (19%) received topical steroids [18, 20, 31], 8 (31%) received locally administered steroids in the form of a triamcinolone injection [20, 26, 27, 29,30,31,32,33], 4 (15%) received immunosuppressive agents [23,24,25, 32], and 1 (4%) received a topical muscarinic antagonist . Two patients (8%) did not receive any treatment, however, of the two, the patient that was on Nivolumab had it tapered [16, 22]. All 26 patients had symptomatic improvement by their final follow up with a complete resolution of the choroidal mass in 65% of patients (17/26) [17,18,19,20,21, 23, 26,27,28, 30, 31, 34,35,36], and regression and stabilization of the mass in 31% of patients (9/26) [15, 16, 22, 24, 25, 29, 32, 33, 36]. There was a visual acuity reporting of 20/20 Snellen equivalent in 38% of cases (10/26) [17, 18, 20, 22, 27, 28, 30, 32] at final follow-up and notable improvement in 38% of cases (10/26) [15, 18, 21, 23, 29, 31, 33, 34, 36] after treatment. Only 1 case reported a gradual worsening in the size of the granuloma, however, the patient had a visual acuity of 20/20 and was observed over the course of 18 years without receiving any treatment .
In our case, the choroidal granuloma was the only clinical manifestation of sarcoidosis, which was discovered after systemic screening for neoplasms was performed. Diagnosis was delayed by a COVID-19 infection which confused the clinical presentation. Of the cases reviewed, only 5 patients had a sarcoidosis diagnosis prior to the identification of the choroidal granuloma [17, 19, 20, 27, 34]. Similarly, to our case, the choroidal granuloma was the initial manifestation of sarcoidosis in the remaining cases we reviewed. This underscores the masquerading quality of an isolated choroidal granuloma, posing a unique diagnostic challenge to clinicians. Therefore, thoroughly investigating the full differential diagnosis of a choroidal lesion – summarized in Table 3 is an important exercise, as there may be an underlying neoplastic process.
Due to its rich vascular supply, the choroid is the most common ocular structure affected by metastasis and the reported mean survival time following a diagnosis of ocular metastasis is 21 months [37, 38]. The most common originating sites of distant metastasis to the choroid include the breast (53%), lungs (20%), and GI tract (4%) . Patients often complain of painless blurry vision but may also note flashes and floaters, pain, or be asymptomatic [37, 39,40,41,42]. Choroidal metastases can be identified on fundoscopy as a yellow subretinal mass located posterior to the equator with subretinal fluid [37, 39]. There are also documented cases of alternative presentations including an orange mass (associated with renal cell carcinoma, carcinoid tumors, thyroid cancers) and brown-gray lesions (associated with metastatic melanoma) [37, 39]. Several imaging modalities can be utilized to aid in the diagnosis of choroidal metastasis. AF commonly identifies subretinal fluid and lipofuscin (scattered clumps of brown pigment) as areas of hyperautofluorescence, while FA demonstrates early hypofluorescence in the arterial phase and late hyperfluorescence in the venous phase [43,44,45,46]. On ultrasound, choroidal metastases appear as echo-dense lesions (B-scan) with high internal reflectivity (A-scan), as opposed to choroidal melanomas which appear as acoustically hollow lesions (B-scan) with low internal reflectivity (A-scan) [37, 47,48,49]. Additionally, OCT’s may be notable for an undulating surface overlying the metastasis and thickening of the retinal pigment along areas of subretinal fluid , and ICG’s typically demonstrate hypocyanescence at all stages [51, 52].
It is also important to consider choroidal nevi and amelanotic choroidal melanomas (ACM) in the differential for a choroidal granuloma. Choroidal nevi are benign tumors of the posterior pole with a reported incidence of 6.5–33% [53, 54]. Of those nevi, 5–6% can be further classified as amelanotic [53, 54]. Choroidal nevi can be identified on fundoscopy as flat, or slightly elevated lesions ranging from slate-gray to an amelanotic yellow white color, with poorly defined margins and often associated with drusen [53,54,55]. On the other hand, ACMs are malignant tumors of the uvea and while rare, are the most common malignant primary intraocular tumor [56,57,58]. They present with prominent vascularity, an accumulation of subretinal fluid, a serous retinal detachment, and lipofuscin with an orange or golden-brown appearance [53, 57, 59]. OCT can be used to identify the presence of retinal disruptions, detachments, debris, and hyperreflective foci [49, 57]. These lesions typically display hyperautofluorescence corresponding to areas of orange pigment on AF [49, 60] and on FA may demonstrate signs of tumor growth such as double circulation, extensive leakage with progressive fluorescence, late staining of the lesions, and multiple areas of pinpoint leaks affecting the retinal pigment epithelium [49, 53, 57]. Additionally, ICG’s can be used to identify deeper areas of microcirculation and smooth, well-demarked areas of hypocyanescence in the late phase [49, 57].
Uveal lymphoma may present similarly to choroidal granulomas with many patients being asymptomatic or having a slow progression of symptoms [61,62,63,64,65]. They can be identified on fundoscopy as multifocal creamy-yellow patches at the level of the choroid often with subretinal fluid, a diffuse distribution, ill-defined margins, and a lack of intrinsic pigmentation [61,62,63,64]. It is best identified using ultrasonography and on B-scan, often appears as an acoustically hollow thickening of the choroid with areas of posterior epibulbar extensions [61,62,63]. On FA, they may present as areas with a granular (leopard spot pattern) appearance and hypofluorescence in the early to mid-phases [66, 67]. Additionally, these granular regions may appear as areas of hyperautofluorescence on AF [66, 67], or as clusters of small hypocyanescent lesions on ICG . OCT’s can also be used to identify segments of the retinal pigment epithelium that are nodular, elevated, hyperreflective, or detached [66, 67].
Although extensive research is being conducted, the etiology of sarcoidosis remains unclear . The current evidence suggests that an unknown antigen triggers an aberrant immune response in a genetically susceptible individual, however, none of the investigated antigens have been significant yet . In the cases of Ung et al.  and Doycheva et al. , immunotherapy agents (Nivolumab and INF-a) had been initiated prior to the development of choroidal granulomas. In both cases patients were weaned off their agents, but only in Doycheva were they started on steroid therapy. Ung et al. reported that their patient was asymptomatic at presentation and upon discontinuation of Nivolumab the size of the granuloma stabilized and did not display progression up to the 1 year follow-up . Doycheva et al. described three separate cases of patients with disrupted vision while on INF-a for chronic hepatitis C. In all three cases, INF-a was tapered, and topical steroids were introduced, but only one case was given systemic steroids. They observed resolution of the mass and improvement in the visual acuity of all three patients .
It is imperative to consider the full differential diagnosis when evaluating a choroidal lesion as the treatment plan will differ significantly depending on the final diagnosis. If there is ever a time where inconsistency between symptoms, fundoscopy, and imaging arises, or there is doubt, a choroidal sarcoid granuloma should be considered. A choroidal granuloma has a wide variety of clinical presentations and can affect both sexes, several racial groups, and a broad age range. It is not always preceded by a diagnosis of sarcoidosis and treatment with corticosteroids is often curative. Therefore, regardless of the characteristics of the patient, it should always be included when considering a differential for a choroidal lesion.
This review summarizes the 26 cases of choroidal sarcoid granuloma in the English language and presents a unique case of a sarcoid granuloma initially mistaken for a choroidal neoplasm. Choroidal granulomas are a rare presentation of ocular sarcoidosis that can impede vision. They are typically yellow lesions, single or multiple, found temporal to or at the macula. Primary testing including fundoscopy, fluorescein angiography, fundus autofluorescence, A/B-scan, and OCT are useful for diagnosing and monitoring response to treatment in patients with a choroidal granuloma. Systemic work-up and ACE levels are helpful in diagnosing atypical choroidal lesions in the absence of a confirmed sarcoidosis diagnosis. Steroids are a mainstay of treatment for sarcoidosis and are effective at treating choroidal granulomas. Early recognition and diagnosis of choroidal granulomas is imperative as treatment can be curative and sight-sparing.
Availability of data and materials
All data generated or analyzed during this study are included in this published article.
Amelanotic choroidal melanomas
Optical coherence tomography
Positron emission tomography
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Hage, D.G., Wahab, C.H. & Kheir, W.J. Choroidal sarcoid granuloma: a case report and review of the literature. J Ophthal Inflamm Infect 12, 31 (2022). https://doi.org/10.1186/s12348-022-00309-y
- Choroidal granuloma
- Ocular sarcoidosis
- Choroidal mass