Masquerade Syndromes


Non-neoplastic

Anterior

Corneal epithelial defects

Angle closure glaucoma

Pigment dispersion syndrome

Occult intraocular foreign body

Drug- and vaccine-induced uveitis

Juvenile xanthogranulomaa

Intermediate

Vitreous hemorrhage

Asteroid hyalosis

Retinitis pigmentosa

Amyloidosis

synchysis scintillans (cholesterolosis bulbi)

Posterior

Ocular ischemic syndrome

Central serous chorioretinopathy

Panuveitis

Scleritis

Rhegmatogenous retinal detachment (Schwartz-Matsu syndrome)

Neoplastic

Anterior

Iris/ciliary body metastasis

Leukemiaa

Langerhans cell histiocytosisa

Iris stromal cyst leakage or rupturea

Intermediate

Primary vitreoretinal lymphoma

Posterior

Choroidal lymphoma

Choroidal melanoma

Choroidal metastasis

Retinal metastasis

Paraneopastic syndromes (CAR, MAR, AEPPVM, BDUMP)

Panuveitis

Retinoblastomaa


CAR cancer-associated retinopathy; MAR melanoma associated retinopathy; BDUMP bilateral diffuse uveal melanocytic proliferation; AEPPVM acute exudative paraneoplastic polymorphous vitelliform maculopathy

aOccur more often in Children





Non-neoplastic Masquerade Syndromes



Anterior Uveitis



Corneal Epithelial Defects


Large or persistent defects in the corneal epithelium can produce moderate to severe anterior chamber inflammation—including hypopyon [2023]. This can occur following large corneal abrasions, after chemical burns, in eyes with neurotrophic keratopathy following herpetic keratitis, in the setting of an underlying corneal dystrophy, or following surgery. It is important to rule out an active infection in such patients.


Primary Acute Angle Closure


Primary acute closure of the anterior chamber angle can produce anterior chamber inflammation associated with elevated intraocular pressure [24, 25], which together can be confused for inflammatory ocular hypertensive syndrome (IOHS) of the sort seen in patients with herpetic anterior uveitis due to herpes simplex, varicella, or cytomegalovirus, sarcoidosis, toxoplasmic retinochoroiditis, and syphilis [26]. Careful examination of the fellow eye can reveal clues to the diagnosis, including an at-risk angle structure and evidence of prior angle closure attacks, such as glaucomflecken on the anterior lens capsule. Unlike IOHS, the anterior chamber inflammation seen in primary acute angle closure tends to resolve promptly with normalization of intraocular pressure (IOP). The prevalence of angle closure is higher in Asians and Asian Indians than in European and Western populations.


Pigment Dispersion Syndrome


Free-floating pigment in the anterior chamber can be mistaken for inflammatory cells. This occurs most commonly in patients with pigment dispersion syndrome (PDS), pigmentary glaucoma, or pigment release following anterior chamber surgery or laser treatment. Pigment dispersion syndrome, in particular, can be confused with chronic anterior uveitis [27]. While high-power slitlamp biomicroscopy can usually distinguish fine, copper-color pigment particles from slightly larger and non-pigmented leukocytes (Fig. 27.1), additional clues that support a diagnosis of PDS include backward bowing of and/or radial slit- or wedge-like transillumination defects in the iris pigment epithelium, pigment deposition on the lens capsule, iris, trabecular meshwork, and corneal endothelium (Krukenberg spindle), and failure to improve following topical corticosteroid treatment. Intraocular pressure may or may not be elevated. Patients with PDS are often relatively young and myopic.

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Fig. 27.1
High-power slitlamp biomicroscopic photographs of the mid-anterior chamber showing relatively larger, non-pigmented leukocytes in a patient with anterior uveitis (a) verses fine, copper-color pigment particles in a patient with pigment dispersion syndrome (b)


Intraocular Foreign Body


Intraocular foreign bodies (IOFB) frequently produce some degree of intraocular inflammation. Traumatic endophthalmitis occurs in a high proportion of such patients and must be considered in the acute setting [28]. Less frequently, a retained IOFB may produce chronic uveitis, which is often only transiently or incompletely responsive to topical corticosteroids [29, 30]. A retained IOFB made of iron can produce the clinical syndrome known as ocular siderosis, which is characterized by deposition of rusty brown pigment on the lens capsule (Fig. 27.2), iris and cornea, mydriasis, pigmentary changes in the retina, attenuation of the retinal vessels, and either hyperemia, or palor of the optic disc, depending on duration. In contrast, a retained IOFB made of copper can produce ocular chalcosis, signs of which include a greenish-blue ring near the limbus (Kayser–Fleisher ring), a sunflower anterior subcapsular cataract, and metallic refractile particles in the anterior chamber and on the retina. A history or signs eye trauma can support the diagnosis. Professions and activities at greatest risk include those involving metal working and the use of motorized machines. Patients with retained IOFB tend to be young and male. Various imaging techniques have been used to locate occult IOFBs, including B-scan ultrasonography, X-rays, magnetic resonance imaging (MRI), and computed tomography (CT). Magnetic resonance imaging should be avoided in eyes suspected of a having a retained metallic IOFB because the IOFB can shift from the magnetic field and lead to ocular damage. High-resolution CT with thin cuts through the orbit is perhaps the most sensitive technique for identifying metal, stone, or glass, but can miss less radio-opaque objects. While listed here as primarily anterior uveitis, patients with retained IOFB may also have inflammatory cells in the vitreous. Some patients with retained IOFB have no active intraocular inflammation.

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Fig. 27.2
High-power slitlamp biomicroscopic photograph showing rusty brown pigment on the anterior lens capsule in a patient with a retained piece of iron resulting in siderosis


Drug- and Vaccine-Induced Uveitis


Although uncommon, a number of drugs and vaccines can induce uveitis [31, 32]. The mechanism(s) of drug-induced uveitis are generally unclear, although both toxic and inflammatory reactions have been suggested to play a role. Systemic agents commonly associated with ocular inflammation include the bisphosphonates—most notably pamidronate sodium, used to treat osteoporosis and to prevent fractures due to malignant bone disease; sulfonamide antibiotics—typically trimethoprim-sulfamethoxazole; tumor necrosis factor-alpha (TNF-α) inhibitors—most notably etanercept [33], and fluoroquinolone antibiotics—especially oral moxifloxacin and to a lesser extent ciprofloxacin [34]. Topical medications strongly implicated as causing uveitis in a minority of patients include the intraocular pressure lowering agents metopranolol, brimonidine, and the prostaglandin analogues. Intraocular agents associated with uveitis include cidofovir, used infrequently to treat viral retinitis, and the anti-vascular endothelial growth factor (VEGF) agents. Uveitis may also occur following vaccination, most notably with Bacille Calmette-Guerin (BCG).


Juvenile Xanthogranuloma


Juvenile xanthogranuloma (JXG) is an uncommon systemic histiocytosis associated with multiple cutaneous papules and, in 0.3–0.4 % of cases, ocular involvement. Infants and children are affected most commonly. While JXG lesions involving the orbit, eyelids and adnexa, conjunctiva, and both anterior and posterior segments have been described, the iris is the most frequently reported site (Fig. 27.3). Iris lesions in JXG are typically circumscribed, nodular, and yellow-white or orange in color—often with intrinsic vascularity. Heterochromia, secondary to recurrent hyphema, may or may not be present [1, 310]. Juvenile xanthogranuloma presenting as a more diffuse and transparent, epi-iridic membrane has also been described, but is rare [35]. Iris JXG lesions are intrinsically benign and often regress in response to topical corticosteroid treatment, but can produce hyphema and elevated intraocular pressure requiring more aggressive treatment. Intra-cameral bevacizumab has been used recently with success [36, 37]. Children with JXG are at increased risk for both neurofibromatosis type 1 (NF1) and juvenile myelomonocytic leukemia (JMML) [35].

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Fig. 27.3
Iris juvenile xanthogranuloma (JXG).Young child with visible iris JXG (a) with intense vascularity that responded to topical corticosteroids (b) over a 1 month period. Young child with ill-defined iris JXG (c) and stringy vascularity that responded to topical corticosteroids (b) over a 2 month period


Intermediate Uveitis



Vitreous Hemorrhage


Vitreous hemorrhage occurs in a number of clinical settings, including patients with proliferative diabetic retinopathy, vitreous or retinal detachment, occlusive retinal vascular disease, intraocular tumors, and trauma [38, 39]. While the clinical recognition of red blood cells in patients with acute vitreous hemorrhage usually offers little challenge, red blood cells can, within one to three weeks, loose both their characteristic biconcave shape and hemoglobin, becoming smaller, round, tan-colored ‘ghost cells’ that may be mistaken for leukocytes. Elevated intraocular pressure that occurs in this setting is referred to as ‘ghost cell glaucoma’ or hemophthalmitis. Formation of a ghost cell pseudohypopyon has also been described [39].


Asteroid Hyalosis


Asteroid hyalosis is an age-related vitreous degeneration of unknown etiology, typically unilateral and more common in men and let common in eyes with posterior vitreous detachment [40] (Fig. 27.4). The characteristic aggregates are composed of calcium hydoxyapatite [41], and far larger than leukocytes, but when relatively few in number and distributed preferentially to the deep vitreous may be mistaken for leukocytes. Prolapse of vitreous hyalosis into the anterior chamber of either aphakic or pseudophakic eyes has been reported to mimic both endophthalmitis and an iris mass [42].

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Fig. 27.4
Asteroid hyalosis (a) found coincidentally in an eye with uveal melanoma, shown on gross pathology (b) following enucleation


Retinitis Pigmentosa


Retinitis pigmentosa (RP) refers to a group of hereditary retinal degenerative disorders characterised by progressive loss of photoreceptors, visual field constriction, worsening night blindness, and decreased or abnormal electroretinographic findings. The condition is bilateral in most patients and is typically diagnoses in childhood or adolescence. Over time, most patients develop widespread disruption of the retinal pigment epithelium with bone spicule formation, arteriolar attenuation, and waxy pallor of the optic disc. Findings usually associated with uveitis, including anterior chamber cell, posterior subcapsular cataract, vitritis, macular edema, vasculitis, and epiretinal membrane formation are not uncommon [1, 310]. Geographic areas of RPE disruption, vascular narrowing, and optic atrophy can also occur following congenital infection by syphilis, toxoplasmosis, rubella, or one of the herpes viruses [43].


Amyloidosis


Amyloidosis refers to a heterogeneous group of disorders characterized by the production and tissue deposition of insoluble, fibrillar proteins known as amyloid. Over two-dozen individual proteins are capable of producing amyloidosis in humans. While the proteins themselves are different, the protein aggregates in amyloidosis share a common beta-pleated sheet configuration. Vitreous amyloidosis, a rare condition that usually occurs in the setting of a hereditary condition known as familial amyloidotic polyneuropathy (FAP), can mimic vitreous inflammation, but can be differentiated by a complete lack of cells and a its characteristically wispy, “glass-wool” appearance (Fig. 27.5). Histological analysis of the vitreous shows positive Congo Red dye staining with “apple-green” birefringence under polarized light [44].

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Fig. 27.5
Color fundus photograph of a patient with amyloidosis showing typical ‘glass-wool’ appearance. High-power slitlamp biomicroscopy of the anterior vitreous would reveal a conspicuous absence of vitreous cells


Synchysis Scintillans (Cholesterolosis Bulbi)


Synchysis scintillans, also known as cholesterolosis bulbi, is a degenerative process of the vitreous characterized by the deposition of cholesterol crystals in the vitreous cavity. While synchysis scintillans can resemble vitritis, the particles in synchysis scintillans have a yellow, glisening appearance, whereas inflammatory cells in the vitreous tend to be more white in appearance and non-glisening. Cholesterol crystals in eyes with synchysis scintillans are typically quite mobile due to advance syneresis.


Posterior Uveitis



Ocular Ischemic Syndrome


Ocular ischemic syndrome (OIS) is an uncommon disorder caused by chronically decreased perfusion of the ophthalmic artery, most typically as a result of ipsilateral carotid artery disease and less frequently as a result of vasculitis. Common symptoms include decreased vision and pain. Anterior segment findings include chemosis, conjunctival or episcleral injection, anterior chamber inflammation, and rubeosis. Posterior segment findings include mild vitreous inflammation, retinal venous congestion, dot-blot hemorrhages in the mid-periphery, and neovascularization. Fluorescein angiography reveals delayed retinal and choroidal perfusion. Patients suspected of having OIS should undergo imaging of their carotid arteries and aortic arch, as well as testing for giant cell arteritis [4547]. Rarely, OIS can occur as a complication of strabismus or scleral buckle surgery [19].


Central Serous Chorioretinopathy


Central serous chorioretinopathy (CSC) is characterized by relative choroidal hyperperfusion producing both retinal pigment epithelial and serous retinal detachments. Men are affected more commonly than woman and many patients have what has been described as a “type A personality” [48]. Serous retinal detachment similar to what is seen in patients with CSC is a well-recognized feature of ocular inflammatory disease, particularly uveitis caused by Vogt–Koyanagi–Harada (VKH) disease [15] and sympathetic ophthalmia [49], leading to occasional misdiagnosis [50, 51]. Whereas the detachments in patients with VKH disease and sympathetic ophthalmia are typically bilateral and invariably associated with vitreous cell, CSC tends to be unilateral and has no vitreous inflammation. In addition, fluorescein angiography of active CSC often reveals distinctive focal RPE leakage and, when chronic, can reveal RPE tracks known as ‘guttering’ that are due to the gravitational effects of persistent subretinal fluid. Corticosteroid administration is an important risk factor for the development of CSC and, infrequently, CSC can occur as a therapeutic complication in uveitis patients receiving corticosteroids [52].


Scleritis


Scleritis is an uncommon disorder characterized by inflammation of the sclera. Whereas anterior scleritis typically produces pain and redness, and is often associated with an underlying systemic vasculitis, pain is less common in posterior scleritis, which is most often idiopathic. Intraocular inflammation, or uveitis, occurs secondarily in approximately 25 % of patients with both anterior and posterior scleritis [53]. The scleral source of the uveitis can be overlooked if the anterior sclera is not examined thoroughly or, in the case of posterior scleritis, B-scan ultrasonography is not performed.


Rhegmatogenous Retinal Detachment (Schwartz-Matsu Syndrome)


Common symptoms of rhegmatogenous retinal detachment (RRD) include floaters, flashes (photopsias or phosphenes) and cloudy or decreased vision –symptoms similar to those experienced by patients with intermediate and posterior uveitis. To complicate matters further, hemorrhage, pigmented cells referred to as ‘tobacco dust,’ (Shafer’s sign) and inflammation can all occur in eyes with RRD. It is important, therefore, that RRD be considered in all eyes with uveitis [1, 310]. A subset of patients with chronic RRD will develop ocular hypertension—a condition known as Schwartz-Matsu syndrome shown to be due to phagocytosed photoreceptor outer segments migrating to and obstructing the trabecular outflow channels [54, 55]. Retinal breaks in patients with Schwartz-Matsu syndrome are often anterior and difficult to localize.


Neoplastic Masquerade Syndromes



Anterior Uveitis



Iris/Ciliary Body Metastasis


Metastasis to the eye is the most common cause of ocular malignancy, occurring in approximately 5–25 % of cancers as a function of both cancer type and stage. Most metastases involve the uveal tract, with the choroid comprising roughly 90 % and iris/ciliary body metastasis constituting the remaining 10 %. Breast and lung cancer are the most common primary sites, with breast cancer tending to occur later in the course of disease, once the diagnosis is established, and lung cancer tending to metastasis earlier (Fig. 27.6). Lung cancer is currently the most common source of iris and ciliary body metastases [3, 8, 1012]. In a large analysis of 104 patients with iris metastases, the primary malignancy arose from cancer of the breast (33 %), lung (27 %), or skin (melanoma) (12 %) [56]. Systemic lymphoma, often aggressive, can also metastasis to the iris. Most lymphomatous iris lesions are B-cell in origin [57]. Anterior chamber inflammation occurs in approximately half of all patients with iris/ciliary body metastasis. Iris neovascularization, hyphema, and ocular hypertension can also occur. Gonioscopy and ultrasonography are important for identifying metastatic lesions as the source of anterior chamber inflammation or hyphema. Fine needle aspiration biopsy and cytopathology can be used to confirm the diagnosis in cases where the diagnosis is uncertain.

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Fig. 27.6
Iris metastasis from breast cancer (a, b) in two different patients, simulating anterior uveitis


Leukemia


Hematopoietic stem cell malignancies are known as leukemias, and may be either acute or chronic, and either lymphocytic or myelocytic. The acute leukemias tend to be comprised of less mature cells and, consequently, are more often aggressive and more likely to involve the eye. While leukemic cells frequently infiltrate the retina and choroid producing leukemic retinopathy and choroidopathy, respectively, these presentations are infrequently mistaken for uveitis. Iris and anterior segment involvement, in contrast, can be confused for uveitis, as the most common signs are iritis and hypopyon, often associated with hyphema, producing a so-called ‘pink hypopyon’ (Fig. 27.7). While iris and anterior segment involvement can be the presenting sign of leukemia, it is more often a sign of relapse [3, 8, 1012]. All patients with a known history of leukemia who develop anterior chamber inflammation should be considered to have a leukemic relapse until proven otherwise.
Aug 17, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Masquerade Syndromes
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