Disc edema, transient obscurations of vision, and a temporal fossa mass

A 56-year-old woman presented with a four-month history of transient obscurations of vision that progressed to constant visual loss. She had a nodular, lumpy-bumpy, cauliflower-like asymmetric edema of the nerve head, which suggested direct optic nerve head invasion with foreign tissue. Imaging of her intracranial contents revealed a well circumscribed gadolinium enhancing mass in the middle fossa. Histopathology of material obtained at craniotomy revealed noncaseating granulomata consistent with sarcoidosis. Central nervous system sarcoid may present either as an infiltrative granulomatous process, or one of discrete tumor mass, masquerading as a neoplasm. Neurologic symptoms and signs often herald the presence of systemic disease. Our illustrates that isolated sarcoid optic neuropathy may occur and be associated with neither intraocular inflammatory signs nor extensive disease elsewhere; indeed, it may be the first declaration of neurosarcoidosis.     

Orbital lesions with granulomatous inflammation

Orbital lesions characterized by granulomatous inflammation are a heterogeneous group of diseases of various causes with a common histopathological substrate involving aggregates of epithelioid cells. Forty-one patients (27 females and 14 males) with biopsy-proven granulomatous inflammation were seen at an orbital clinic between 1978 and 1989. The mean age at presentation was 40.2 (extremes 6 and 77) years. Two main clinical presentations were noted: painless, subacute or chronic mass effect, and tender, subacute inflammatory process. Six patients had secondary features that were infiltrative in character. The lesions were primarily located in the anterior superior orbit. In nearly half the patients the granulomatous reaction was confined to the orbit (predominantly ruptured dermoid and localized orbital sarcoid), and the remainder had either regional involvement (Wegener's granulomatosis or fibro-osseous process) or systemic involvement (sarcoidosis).     

Angiotensin-converting enzyme in sarcoid uveitis.

The diagnosis of ocular sarcoid is presumptive in the absence of systemic disease. The association of elevated serum angiotensin-converting enzyme (ACE) levels with active systemic sarcoid has been well described. With a sensitive fluorimetric assay for ACE, we found that five of ten chronic granulomatous uveitis patients without systemic sarcoid had elevated serum ACE levels. None of ten patients with uveitis of known etiology had elevated serum ACE levels. We believe that the association of an elevated serum ACE level with chronic granulomatous uveitis suggests the diagnosis of ocular sarcoid.     

Optic nerve involvement in sarcoidosis

Six patients with generalized histologically confirmed sarcoidosis developed optic nerve involvement, two at the onset and four during the chronic course of the disease. Two patients had granulomata of the prelaminar part of the optic nerve, two patients had optic disc oedema with an unusual appearance, one had a retrobulbar optic neuritis and one a glaucomatous cupping of the optic nerve head. Four patients had no visual complaints at the time the sarcoid optic nerve abnormality was detected. The wide variety of the ophthalmos-copical appearance of the sarcoid optic nerve affection and the patients' neuro-ophthalmic and otherclinical findings is discussed. The fluoresceinangiography of thegranulomatosis of the optic nerve showed an early hypofluorescence typical of a sarcoid mass lesion.     

Elimination of immune precipitates from the rat corneal stroma: a histological study

The pathogenesis of peripheral corneal lesions of immune aetiology, like Mooren's ulcer and catarrhal infiltrates, has been related to the formation or deposition of immune compkexes. The present investigation was undertaken to study the mechanisms involved in the elimination of immune precipitates from the cornea. Immune precipitates were induced by injecting human serum albumin (HSA) and rabbit anti-HSA serum into opposite sites of the rat corneal stroma. This resulted in a line-shaped opacity in the stroma, which remained visible by slit-lamp for 7 days, and disappeared without clinical signs of keratitis and uveitis. At the ultrastructural level, the immune precipitates were clearly visible. Keratocytes in the vicinity of the immune precipitates appeared activated, as suggested by their less flattened appearance and well-developed rough endoplasmic reticulum. The arrangement of the collagen fibrils was not affected. Cells with a macrophage-like morphology were also present and contained electron-dense material, closely resembling the precipitate, suggesting phagocytosis. Separate corneas were injected with latex beads, which is known to induce migration of Langerhans cells into the cornea. Immunohistochemical analysis revealed that both latex beads and immune precipitates induced migration of macrophages (ED1+) into the rat corneal stroma. However, differences were observed with regard to the expression of MHC class II antigens by these ED1+ cells and the presence of complement deposits in the corneal stroma. ED1+ cells in corneas injected with latex beads were all MHC class II positive (OX4+), whereas most of the ED1+ cells at the site of the immune precipitates were negative (OX4-).(ABSTRACT TRUNCATED AT 250 WORDS)     

Giant sarcoid tumor of the iris and ciliary body

PURPOSE: To report the occurrence of a giant iridociliary sarcoid tumor. METHODS: The patient was evaluated by medical history, ophthalmoscopic examination (including photography and ultrasonography) as well as systemic, hematologic, and radiographic examinations. Tumor biopsies allowed for cytopathologic, histopathologic, and immunohistochemical analysis. RESULTS: The 39-year-old black male was found to have a right iris and ciliary body tumor. Ultrasonography revealed a 10 x 12-mm base, 5.6-mm height, low internal reflectivity, and vitreous debris. Radiographic imaging revealed mediastinal and bilateral hilar lymphadenopathy. A purified protein derivative (PPD) and a hematologic survey were negative. Pathology evaluations of the surgical specimens revealed features of non-caseating granulomata consistent with sarcoidosis. A combination of topical and systemic steroid therapy was locally curative. CONCLUSIONS: We describe a giant iridociliary sarcoid tumor in a patient with no lacrimal gland enlargement, conjunctival nodules, or skin lesions. A biopsy was required to establish the diagnosis.     

Phenotypes of conjunctival inflammatory cells in sarcoidosis.

Phenotypes of the infiltrating mononuclear cells of the lower fornix conjunctiva of nine patients with sarcoidosis and six controls were studied using monoclonal antibodies and a modified immunoperoxidase method. Four patients had sarcoidosis of recent onset (duration of 2 years or less) and five patients had a chronic disease (duration of 3 or more years). The inflammatory cells in the sarcoid conjunctival specimens were predominantly T lymphocytes, the vast majority of which were of T helper/inducer subtype expressing Leu-3a + 3b positivity. The ratio of T helper/inducer cells to T suppressor/cytotoxic cells was 3.9 on average but only 0.9 in controls. Epithelioid cell granulomas were seen in three specimens in one case of recent onset and in two chronic cases comprising a marked amount (more than 15 cells/visual field) of cells bearing phenotypes of macrophages, T cells, T helper/inducer cells and HLA-DR antigen, and in smaller quantities of T suppressor/cytotoxic cells. The mean number of all immunocompetent cell subtypes of specimens from newly diagnosed patients exceeded that of specimens from chronic patients. We believe that the sarcoid immune reaction in the conjunctiva is a dynamic process in which proliferation of immunocompetent mononuclear cells precedes the stage of granuloma formation.     

Presumed Intraocular Tuberculosis Manifesting as Unilateral Iris Granuloma

ABSTRACT

Ocular tuberculosis can manifest in a wide variety of clinical presentations. The prevalence is higher in endemic areas as a cause of granulomatous uveitis. While posterior segment manifestations are well known, anterior segment granulomas alone are relatively rare. We report two cases of unilateral iris granulomata in two young patients who presented with decreased vision and redness and were found to have well-circumscribed iris granulomas. Both underwent systemic evaluation and had a negative Mantoux test. Biopsy pathology of the lesions revealed granulomatous inflammation but were negative for PCR, staining, and culture for TB. One patient turned out to have multiple pulmonary lesions. The ocular condition initially worsened with steroid therapy alone and improved and resolved completely after starting a 9 months course of anti-tubercular therapy (ATT).     

Systemic CD4(+) T cell phenotype and activation status in intermediate uveitis

AIM: To investigate peripheral blood lymphocyte phenotype in patients with intermediate uveitis using CD69, chemokine receptor, and cytokine expression. METHODS: Peripheral blood lymphocytes of 18 patients with idiopathic intermediate uveitis and 6 patients with presumed sarcoid intermediate uveitis were evaluated for CD4(+) T cell expression of CD69, CCR4, CCR5, CXCR3 and the intracellular cytokines IFNgamma, TNFalpha, and interleukin (IL)-10 by flow cytometry, and for IL-2, IL-4, IL-5, IL-10, IFNgamma, and TNFalpha production following unstimulated and activated culture using cytokine bead array and compared with healthy control subjects. RESULTS: The expression of CD69 and TNFalpha by peripheral blood CD4(+) lymphocytes of patients with idiopathic intermediate uveitis and presumed sarcoid intermediate uveitis was significantly higher than control subjects (p = 0.002 and p<0.05, respectively). The ratios of the concentrations of IL-2:IL-5 and IFNgamma:IL-5 in supernatants of activated peripheral blood lymphocyte cultures were significantly higher in patients with presumed sarcoid intermediate uveitis than control subjects. CONCLUSIONS: This study implicates TNFalpha in the pathogenesis of intermediate uveitis, highlighting the potential role of anti-TNF treatments for this disease. Studies of Th1:Th2 cytokine ratios suggested polarisation of the immune response towards Th1 in presumed sarcoid intermediate uveitis despite clinically quiescent systemic disease.     

Clinical and Investigative Profile of Biopsy-Proven Sarcoid Uveitis in India

Purpose: Retrospective analysis of the clinical features, investigative profile, response to treatment, and final visual outcome in histopathologically confirmed cases of sarcoid uveitis. Methods: Retrospective case series analysis was done of 15 eyes of 9 patients seen between July1999 and August 2003 with biopsy-proven sarcoid uveitis. There were 3 were males and 6 females. The mean age at presentation was 44.1 years (range 11–62 years), The mean follow-up was 28.4 months. Results: Six patients had bilateral ocular involvement and 3 had unilateral involvement. Five out of 9 patients had primarily ocular involvement. The most common presentation was intermediate uveitis and granulomatous anterior uveitis in 7 patients. Eight of 9 patients responded well to the medical treatment with systemic and periocular steroids. Conclusions: Ocular lesions can be the primary manifestation of systemic sarcoidosis. Sarcoid uveitis in the Asian Indian population often presents an intermediate uveitis with granulomatous anterior uveitis.     

Angiotensin-converting enzyme in sarcoid and chalazion granulomas of the conjunctiva

Angiotensin-converting enzyme (ACE) was studied immunohistochemically in conjunctival biopsies from 6 patients with systemic sarcoidosis, 4 patients with posterior non-sarcoid uveitis and in specimens from 4 patients with chalazion of the eyelid. Specimens with sarcoid granulomas showed intense ACE-positive immunoreactivity in epitheloid cells of the granuloma, whereas chalazion granulomas did not contain ACE-immunoreactivity. There was no difference in staining patterns between specimens without granulomas. Thus immunohistochemical staining for ACE may be of help in differentiating conjunctival granulomatous tissue of a chalazion from sarcoid granuloma.     

Three ocular sarcoidosis patients examined by indocyanine green angiography]

PURPOSE: To assess the findings of indocyanine green angiography(IA) in patients with ocular sarcoidosis. SUBJECTS AND METHODS: Three active ocular sarcoidosis patients with various retinochoroidal findings diagnosed by biopsy or systemic examination. Two patients were diagnosed pathologically and one patient was diagnosed clinically. IA & fluorescein angiography(FA) were performed before and after treatment with systemic steroid administration. RESULTS: IA revealed hyperfluorescence surrounding the presumed granulomatous lesions. This hyperfluorescence disappeared immediately after the treatment. FA showed hyperfluorescence continuing even after therapy. CONCLUSIONS: It is purposed that the ring-form hyperfluorescence in IA is due to accelerated vascular permeability in the active sarcoid granuloma. IA, which vividly reflects activity of sarcoid lesions, is an important tool for clinical evaluation of ocular sarcoidosis.     

Upper and lower eyelid reconstruction for severe disfiguring necrobiotic xanthogranuloma

BACKGROUND Necrobiotic xanthogranuloma is a rare disease featuring generalized xanthomatous inflammatory skin lesions associated with paraproteinemia and possible lymphoproliferative diseases. Eyelid involvement can be unilateral or bilateral and ranges from minor xanthelasma-like lesions to severe ulcerative disease with consecutive keratitis and scleritis. CASE REPORT The authors report the case of a 67-year-old woman with extensive necrobiotic xanthogranuloma involving the eyelids, head and neck, anterior chest, and both upper and lower extremities. Periorbital involvement caused severe upper and lower lid ectropium with chronic conjunctival inflammation and unilateral exposure keratitis. During a persistent period of low disease activity, granulomatous lesions and scars were widely excised, lids partially shortened and large full-thickness skin grafts applied. Uninvolved parts of the upper arms had to serve as donor sites, as other possible donor sites were not available. After successful reconstruction of the left side and no local recurrence of the disease, the right side was corrected in the same way. Full eyelid closure was achieved and skin grafts healed without complications. No recurrence of the disease appeared at the sites of operation, despite continuous new lesions elsewhere. CONCLUSION Severe cicatricial eyelid deformation caused by necrobiotic xanthogranuloma can be treated with success by excision and free skin grafting. The mechanisms of recurrence at excision sites described by others remain unclear, but at least during phases of low activity, the described treatment is safe and recurrence is not to be expected.     

EMAP-II expression is associated with macrophage accumulation in primary uveal melanoma

PURPOSE: Primary uveal melanoma may contain arcs, loops, and networks of periodic acid-Schiff (PAS)-positive patterns, along which numerous macrophages are present. Their recruitment into tumor tissue is mediated by chemotactic cytokines, for which vascular endothelial growth factor (VEGF)-C and endothelial monocyte-activating polypeptide ((EMAP)-II are candidates. In this study, the extent of VEGF-C and EMAP-II immunoreaction was related to infiltration of macrophages. METHODS: Serial sections of 25 primary uveal melanoma lesions were analyzed by immunohistochemistry. RESULTS: The analysis showed no correlation of VEGF-C immunoreaction and localization of macrophages. However, accumulation of macrophages occurred at sites of EMAP-II expression, especially in areas containing nests of tumor cells, surrounded by arcs, loops, and network patterns. In tumors with a strong EMAP-II immunoreaction, the adhesion molecule intracellular adhesion molecule (ICAM)-1 was strongly expressed on endothelial cells. EMAP-II-positive endothelial cells did not express VEGF receptor-2. However, extensive release of von Willebrand factor was observed. Signs of apoptosis were found neither in tumor cells nor endothelial cells. CONCLUSIONS: In uveal melanoma, macrophages accumulate at sites of EMAP-II expression. Based on the results, it may be hypothesized that this process of chemotaxis is facilitated by EMAP-II-dependent expression of ICAM-1 on vascular endothelial cells and concomitantly leads to localized vascular damage, as indicated by release of von Willebrand factor.     

Morphology of the fibrinogen exudate during evolution of a mycobacterial-induced murine eye granuloma

The intent of this study was to visualize changes in the density and location of fibrinogen-related antigen (FRA) depositions within the murine vitreous space during the formation of a chronic mycobacterial-induced uveitis (CMIU) granuloma. Concurrent changes in cellular morphology of the granuloma were also examined. Fibrinogen derivatives within the exudates of granulomatous cell-mediated inflammations may induce physical induration and numerous other phlogistic effects. However, technical limitations of conventional FRA staining methods have tended to underestimate the extent of their presence within this category of inflammatory lesions. Conventional H and E sections of the CMIU granuloma confirmed the classic progression-early PMN influx, monocyte maturation and final macrophage and epithelioid cell dominance-described for such lesions. Avidin-biotin-complex staining utilizing a polyclonal mouse antifibrinogen then revealed a progressive increase in amorphous extracellular fibrinogen-FRA-positive staining material as the granuloma evolved. Thus, on day one the PMN influx showed no evidence of fibrinogen-FRA staining; at one week heavy staining was evident in the anterior chamber and in consolidated (i.e. macrophage) regions of the granuloma; at one month a heavy uniform staining appeared throughout the indurated granuloma where macrophages and epithelioid cells predominated. Patterns of heavy deposition on macrophage surfaces were suggested. The likelihood that bulky accumulations of FRA in mature granulomas are not solely fibrin, and may account for granulomatous induration and persistence, is discussed.     

Rare Association of Perivascular Granulomatous Lesions in a Patient with Acute Retinal Necrosis

Purpose

The aim of this study was to examine sequential changes in perivascular granulomatous lesions with acute retinal necrosis (ARN).

Methods

A healthy 46-year-old Japanese woman, who developed floaters and pain in her left eye, underwent optical coherence tomography (OCT), fluorescein angiography, and routine ophthalmological examinations. Treatment-associated changes in perivascular granulomatous lesions were monitored using spectral-domain (SD)-OCT.

Results

The patient had no previous ophthalmic history, and her general condition was good. A slit-lamp examination revealed keratic precipitates and aqueous cells (2+) in the left eye. A fundus examination showed yellow-white patches of necrotizing retinal lesions in the temporal upper area, retinal arteritis, retinal hemorrhage, and vitreous opacities. The patient was diagnosed with ARN according to diagnostic criteria. SD-OCT images confirmed high-intensity and uniform granulomatous deposits in the perivascular area and fovea. Systemic corticosteroids and antiviral therapy were initiated, resulting in the gradual resolution of granulomatous lesions. The patient continues to be followed untreated without evidence of recurrence, retinal detachment, or active inflammation.

Conclusions

This is the first report of perivascular granulomatous lesions in a patient with ARN. Our results showed that the formation of granulomas may be induced in the retina of ARN patients without fulminant inflammation.Key Words: Acute retinal necrosis, Optical coherence tomography, Granuloma     

Immunohistology of antigen-presenting cells in vivo: a novel method for serial observation of fluorescently labeled cells

PURPOSE: Dendritic cells and macrophages are phagocytic antigen-presenting cells that bridge the innate and acquired immune systems. The coexistence of subtypes of dendritic cells and macrophages with overlapping properties complicates resolution of their precise roles in an immune response within a given tissue. This report documents a method to identify and observe these cells over time in a living animal and thereby to visualize them during a dynamic immune response. METHODS: To label potential antigen-presenting cells, fluorescently tagged ovalbumin was injected into the anterior chambers of mouse eyes. Fluorescently tagged antibodies to cell surface proteins were injected to label specific cell types. Intravital fluorescence microscopy with digital image recording was used to visualize the labeled cells in the irises at various times after the injection. RESULTS: The pattern and density (116-148 cells/mm(2)) of cells labeled in vivo by fluorescent ovalbumin or F4/80 antibodies were similar to that identified by conventional wholemount immunostaining for macrophages and dendritic cells. Fluorescent antibodies specific for CD11b, CD11c, CD80, CD86, or major histocompatibility complex (MHC) class II protein each labeled selective populations of cells in vivo. In contrast to conventional histology, in vivo immunohistology permitted serial observations. The phenotype of cells labeled by fluorescent ovalbumin was not the same at 6 (95% CD11c(+)) and 24 hours (24% CD11c(+)) after injection. CONCLUSIONS: This method of in vivo immunohistology provides a tool for studying cell kinetics and dynamic interactions that cannot be assessed by conventional immunohistology. Furthermore, it avoids potential artifacts from tissue fixation and may work with antibodies that label cells poorly in vitro.     

Unilateral chronic granulomatous blepharitis as a leading symptom of Oriental cutaneous leishmaniasis in Germany. Giesma stain as rapid diagnosis and initial description of systemic therapy with gamma-interferon]

Nine months after leaving the Lebanon, a four-year-old immigrant boy presented with a 5 months history of blepharitis. The lesion remained therapy-resistant for aminoglycoside antibiotics. Six months later, the patient presented with an indolent granulomatous necrotizing purulent blepharitis and follicular conjunctivitis. Diagnosis was made by Giemsa stain and histopathology, which revealed amastigotes in macrophages consistent with the diagnosis of oriental cutaneous leishmaniasis. Therapy with systemic recombinant gamma Interferon, which is described for the first time in this disease entity, resulted in a successful primary healing of the cutaneous lesion. Self-healing epithelial keratitis was the only side-effect observed. Ophthalmologists in Germany should be aware of the differential diagnosis of oriental cutaneous Leishmaniasis in patients suffering from chronic granulomatous lid lesions of patients from countries endemic/epidemic for Leishmaniasis. Laboratory diagnosis is simple. Insights into the immunology of infection have made possible novel therapeutic avenues using gamma-Interferon being effective without serve side-effects and allowing for a good primary healing of the cutaneous lesions.     

Sarcoidosis

Sarcoidosis is a multisystem granulomatous disease with an unknown etiology, characterized by the presence of noncaseating granulomas in involved organs. It has a worldwide prevalence, but variable incidence among different geographical regions. The disease affects adults between 20 and 40 years of age, and it is slightly more common in women than men. Sarcoidosis is 3 to 4 times more prevalent in US blacks than whites. It usually presents with bilateral hilar adenopathy, pulmonary infiltrates and skin or eye involvement. The eye or adnexa are affected in 25 to 80% of the sarcoidosis patients. The disease can involve the orbit, lacrimal gland, anterior and posterior segments of the eye. Typical sarcoid uveitis presents with bilateral mutton-fat keratic precipitates, cells, flare, iris nodules, anterior and posterior synechia, and increased ocular pressure. Posterior involvement includes vitreitis, vasculitis, choroidal lesions, and optic neuropathy. Long term complications are common, and cystoid macular edema is the most important and sight-threatening consequence. Laboratory tests for the diagnosis of sarcoidosis include chest radiography or CT scan, bronchoscopy with bronchoalveolar lavage, angiotensin converting enzyme (ACE), Lysozyme, serum and urinary calcium, gallium scintigraphy, and biopsy. The only confirmatory test is biopsy showing classic noncaseating granulomas. Oral corticosteroids are the mainstay of treatment of sarcoidosis. Systemic cytotoxic agents like methrotrexate, azathioprine, and chlorambucil may be used in refractory cases. The visual prognosis of sarcoidosis is usually good.