Vinicius S. Saraiva

Pathological and prognostic features of uveal melanomas

Uveal melanomas may arise in the iris, ciliary body or choroid. Choroidal melanomas are the most common and usually display a discoid, collar-button or mushroom-shaped growth pattern. Uveal melanomas are composed of spindle and epithelioid cells and are classified histopathologically as either spindle-cell-type or mixed-cell-type tumours. The most important factors predicting clinical behaviour and underlying biology are cell type, cytomorphometric features, largest tumour dimension, scleral invasion and mitotic figures. Other valuable prognostic factors are tumour-infiltrating lymphocytes and macrophages, and the presence of vascular loops.

Treatment of cystoid macular edema related to retinitis pigmentosa with intravitreal triamcinolone acetonide.

A case of cystoid macular edema related to retinitis pigmentosa treated with intravitreal injection of triamcinolone acetonide is described. A 30-year-old white man with retinitis pigmentosa and progressive visual loss presented with a best-corrected visual acuity of 20/40 in the right eye and 20/80 in the left eye. Examination revealed cystoid macular edema in both eyes. After failure of treatment with oral acetazolamide, intravitreal injection of 0.1 mL of triamcinolone acetonide 0.4% solution was performed in both eyes. In the left eye, macular edema resorbed and visual acuity improved to 20/50. However, 6 months after injection, visual acuity worsened because of recurrence of cystoid macular edema. In the right eye, cystoid macular edema also resorbed, but visual acuity was unchanged. Intravitreal triamcinolone acetonide may be useful for selected cases of cystoid macular edema related to retinitis pigmentosa.

Immunohistochemical expression of phospho-akt in uveal melanoma

The aim of this study was to evaluate the immunohistochemical expression of phospho-Akt and its possible association with clinicopathological features in uveal melanoma. Thirty-four enucleated eyes from 34 patients with choroidal melanoma were included in the study. Patients were divided into two groups based on the treatment received: (1) primary enucleation (n=18); (2) radiotherapy, either external beam or brachytherapy, and enucleation (n=16). Clinicopathological data were obtained. The minimum follow-up time was 72 months. Immunohistochemistry for phospho-Akt was performed using an anti-phospho-Akt (Ser 473) rabbit antibody. The association of phospho-Akt with clinicopathological parameters was investigated in each patient group separately. Phospho-Akt immunostaining was cytoplasmic in both groups. In the primary enucleation group, 10 tumours were phospho-Akt positive (55.5%). Patients with phospho-Akt-positive tumours were older (average 70.8 years versus 59 years, P=0.01) and phospho-Akt immunoreactivity was significantly associated with a higher risk of metastatic disease (Kaplan–Meier analysis, P=0.02). In the radiotherapy and enucleation group, nine tumours were phospho-Akt positive (56.2%). The absence of phospho-Akt expression was correlated with male gender (P=0.02). The following conclusions can be drawn from this study: (1) phospho-Akt immunoexpression was detected in 55.5% of uveal melanomas treated with primary enucleation and in 56.2% of uveal melanomas treated with radiotherapy and enucleation; (2) the association of phospho-Akt immunoexpression with clinicopathological features, including prognosis, merits further study.

Cytotoxic effects of violacein in human uveal melanoma cell lines.

Violacein is the main pigment produced by Chromobacterium violaceum, a saprophytic gram-negative bacillus. Violacein is formed by the condensation of two modified tryptophan molecules and has potential anti-neoplastic effects. The purpose of this pilot study was to investigate the in vitro activity of violacein in human uveal melanoma cell lines. Human uveal melanoma cell lines 92.1 and OCM-1 were incubated with five different concentrations of violacein (10−5–10−9 M), and the total cellular protein content was measured by means of the sulphorhodamine B assay. Dose–response curves were obtained and the concentration inhibiting cell growth by 50% (IC50) together with the concentration inhibiting the net cell growth by 50% (GI50) were calculated for both cell lines. Violacein IC50 and GI50 concentrations to cell line 92.1 were 2.78×10−6 M and 1.69×10−6 M, respectively. The IC50 and GI50 concentrations to cell line OCM-1 were 3.69×10−6 M and 2.12×10−6 M, respectively. Previous studies using the same methodology have revealed violacein to have a GI50 in the range (3–6)×10−8 M for MOLT-4 leukaemia, NCI-H460 large cell lung cancer and KM12 colon cancer cell lines. Violacein displayed borderline cytotoxic activity in human uveal melanoma cell lines 92.1 and OCM-1, as measured by the sulphorhodamine B assay, and further studies are necessary to define its suitability as a potential therapeutic agent for metastatic uveal melanoma.

Immunohistochemical expression of melan-A and tyrosinase in uveal melanoma

Background Melan-A and tyrosinase are new immunohistochemical markers that can be used in the diagnosis of melanocytic lesions. The aim of this study was to investigate the correlation between radiotherapy or clinicohistopathological parameters and the expression of melan-A and tyrosinase in uveal melanoma. Methods Thirty-six enucleated cases of uveal melanoma were studied. The formalin-fixed, paraffin-embedded specimens were immunostained with monoclonal antibodies against melan-A and tyrosinase. The samples were classified as either positive or negative. The chi-square or the Student-t tests were used to test for the correlation of the expression rates of melan-A and tyrosinase with clinico-pathological parameters. Results Melan-A and tyrosinase were positive in 33 (91.7%) and 35 (97.2%) of the specimens, respectively. There was no significant association between the expression of melan-A or tyrosinase and radiotherapy or any clinico-pathological parameter. All specimens were positive for at least one of the immunohistochemical markers. Conclusion To the best of our knowledge this is the first study concluding that the expression of melanocytic markers such as melan-A and tyrosinase is not influenced by radiotherapy or any clinico-pathological parameter. Moreover, when tyrosinase and melan-A are used together, 100% of the formalin-fixed, paraffin-embedded uveal melanoma samples tested positive for one of those markers.

Cost considerations of the new fixed combinations for glaucoma medical therapy

Objective:  To compare the costs of the new fixed combinations for glaucoma medical therapy.

Treatment of Cystoid Macular Edema Related to Retinitis Pigmentosa with Intravitreal Triamcinolone Acetonide: Case Report

Cystoid macular edema is an important cause of central visual loss in patients suffering from retinitis pigmentosa (Weleber et al., 2001). A few treatment modalities have been described, including the use of carbonic anhydrase inhibitors and grid laser photocoagulation (Fetkenhour et al., 1977).

Immunohistochemical profile of lymphoid lesions of the orbit

BACKGROUND Orbital idiopathic inflammation, lymphoid hyperplasia, and lymphoma may all present clinically in the same manner. Histopathology and especially immunohistochemistry play a major role in the differential diagnosis. The purpose of this study was to determine the immunophenotypic features of these lesions. METHODS Fifty-five orbital lymphoid lesions were retrieved from the ophthalmic pathology registries at McGill University, Montreal, Canada, and the Federal University of São Paulo, São Paulo, Brazil. Formalin-fixed, paraffin-embedded, histopathologic sections were stained with hematoxylin and eosin and periodic acid-Schiff. The sections were also immunostained for B-cell (CD20) and T-cell (CD43) markers and for immunoglobulin light chains kappa and lambda. Two pathologists determined the histopathologic and immunohistochemical pattern of each lesion in a masked fashion. RESULTS Of the 55 lesions, 11 (20%) were idiopathic chronic inflammations, 22 (40%) were lymphoid hyperplasias and 22 (40%) were lymphomas. Idiopathic inflammation displayed a predominance of T cells and all lesions expressed polyclonal light chains. Lymphoid hyperplasia displayed a mixture of B cells and T cells, with a slight predominance of the former and all lesions expressed polyclonal light chains. Lymphoma showed a striking predominance of B cells and all lesions expressed monoclonal light chains, usually kappa (63.7%). The differences in the mean percentages of B cells among the orbital lymphoid lesions (inflammation, 35%; hyperplasia, 65.9%; lymphoma, 87.3%) were statistically significant (p < 0.001). INTERPRETATION Orbital lymphoid lesions can be differentiated based on the percentages of B cells and T cells and the monoclonal or polyclonal expression of immunoglobulin light chains.

Secretion of hepatocyte growth factor and vascular endothelial growth factor during uveal melanoma-monocyte in vitro interactions.

Host–tumour interactions in uveal melanoma, and their involvement in the biological events leading to metastasis and eventually mortality, are not well understood. It is known that uveal melanoma disseminates predominantly via a haematogenous route with metastasis developing primarily in the liver. Therefore, cytokines involved in angiogenesis, such as vascular endothelial growth factor (VEGF), and those expressed in large quantities within the liver, such as hepatocyte growth factor (HGF), are of particular interest in uveal melanoma research. This study investigated the levels of HGF and VEGF in monocyte and uveal melanoma-conditioned medium. Five human uveal melanoma cell lines and one monocyte cell line were seeded in six-well plates. After 18 h, melanoma-conditioned medium (MCM) was placed on the monocyte cell line and monocyte-conditioned medium (MoCM) was placed on each uveal melanoma cell line. Tumour cells and monocytes incubated in fresh, as opposed to conditioned, medium after 18 h were used as controls. VEGF and HGF levels were determined by immunoassay prior to media transfer and 6, 12, 24 and 36 h thereafter. Both cytokines showed an upregulation of expression from all cells after incubation in conditioned medium. 28SC incubated in MCM expressed higher levels of the given cytokines than did uveal melanoma cells incubated in MoCM. In addition, each cell line exhibited a distinct pattern of expression, with individual cell lines exhibiting different peak levels of cytokine production at different time points. These results offer insight into the upregulation of VEGF and HGF, which may play a role in tumour–host cell interactions.

A case of anterior internal ophthalmomyiasis: case report

A case of anterior internal ophthalmomyiasis is described. A 27-year-old female from Northern Brazil presenting with anterior uveitis and vitritis had a fly larva surgically removed from the anterior chamber of the left eye. The species was Cochliomyia hominivorax. The larva was covered by macrophages and foreign body giant cells characterizing a foreign body granulomatous reaction.