Clinical Features and Prognostic Factors in Presumed Ocular Tuberculosis.

PURPOSE: To characterize the clinical features in patients with presumed ocular tuberculosis (TB) and determine prognostic factors of visual outcomes and complications in this disease. MATERIAL AND METHODS: Retrospective case series of 35 patients (29 females, 6 males) with presumed ocular TB from referral centers in Chile and Spain between 2002 and 2012. Medical records were reviewed, and data regarding clinical features, complications, best-corrected visual acuity (BCVA), duration of disease, extraocular manifestations, and therapy were retrieved. Prognostic factors for low vision (BCVA 20/50 or less), legal blindness (BCVA 20/200 or less), and complications (cataract, glaucoma, and macular lesion) were evaluated. To calculate correlations, we used Spearman's rank correlation test. To determine clinical predictors, we used the binary logistic regression test. RESULTS: Anterior and non-granulomatous uveitis was the most common types of inflammation. Only 2 (5.7%) patients had respiratory symptoms, and 6 (17.1%) patients had an abnormal chest X-ray at diagnosis. All patients received combined antitubercular therapy with a mean duration of 6.9 ± 2.3 months. A longer duration of symptoms at diagnosis was associated with both low vision and legal blindness. Older patients had a higher risk of legal blindness. A longer duration of symptoms as well as anterior inflammation demonstrated an increased risk for cataract formation. The duration of the symptoms and baseline BCVA had a positive correlation with the final BCVA. Prognostic factors of macular lesions were not found. CONCLUSIONS: The diagnosis of ocular TB can be difficult due to the lack of extraocular manifestations and the broad spectrum of ocular features. A longer duration of symptoms at diagnosis was associated with poorer visual outcomes and cataracts. Therefore, efforts should be made to avoid a delay in the diagnosis of ocular TB and to identify prognostic factors for visual outcomes and complications.

Evaluation of the Accuracy of T-SPOT.TB for the Diagnosis of Ocular Tuberculosis in a BCG-vaccinated, Non-endemic Population.

PURPOSE: To determine the performance of T-SPOT.TB, an interferon gamma release assay test, in patients with ocular tuberculosis (TB) in a BCG-vaccinated, non-endemic population. METHODS: We employed a nested case-control design. In total, 45 subjects were enrolled (23 patients with ocular tuberculosis and 22 patients with other causes of uveitis). A blood sample was collected from each subject, and T-SPOT.TB was executed. Laboratory professionals were blinded to the disease status of each subject. RESULTS: Five patients were excluded because of indeterminate results. The calculated sensitivity and specificity were 0.80 and 0.85, respectively. The positive likelihood ratio was 5.33 and the negative likelihood ratio was 0.23. The overall accuracy of the test was 0.83. CONCLUSIONS: T-SPOT.TB adequately diagnosed ocular TB. This technique is particularly useful in populations where BCG vaccinations are still mandatory.

Mycophenolate Mofetil Therapy in Refractory Inflammatory Eye Disease.

PURPOSE: To study the efficacy and incidence of treatment-related side effects of mycophenolate mofetil (MMF) therapy in patients with noninfectious inflammatory eye diseases. METHODS: Retrospective cohort study of 27 Chilean patients treated for noninfectious inflammatory eye diseases using MMF therapy over a 10-year period. Main outcome measures were: ability to control ocular inflammation and to taper prednisone to ≤10 mg daily (treatment success); incidence of treatment-related side effects. RESULTS: The proportion of patients with sustained control of inflammation was 81.48% at 6 months. Additionally 55.56% and 22.22% of patients succeeded in tapering their prednisone to 5-10 mg/day and <5 mg/day, at 6 months. Two patients developed a neoplasia during MMF therapy; however, this cohort is too small to interpret the significance of this relation to MMF treatment. CONCLUSIONS: MMF seems to be an effective corticosteroid-sparing agent with an acceptable safety profile.

Imatinib mesylate alters the expression of genes related to disease progression in an animal model of uveal melanoma.

Imatinib mesylate (IM) is a compound that inhibits both BCR-ABL tyrosine kinase and c-kit receptors. Tyrosine kinases are important in cellular signaling and mediate major cellular processes such as proliferation, differentiation, apoptosis, attachment, and migration. Twenty-six albino rabbits were injected with 1 × 10(6) human uveal melanoma (UM) cells (92.1) into the suprachoroidal space. Animals were immunosuppressed (cyclosporin A) over the course of the 12-week experiment and divided into two groups (n = 13). The experimental group received IM once daily by gavage while the control group received a placebo. One animal per group was sacrificed every week after the 2nd week. Upon necropsy, organs were harvested for histopathological examination. Cells from the primary tumors were recultured and tested in proliferation and invasion assays. A PCR array was used to investigate the differences in expression of 84 genes related to tumor metastasis. In the treated group, 4 rabbits developed intraocular tumors, with an average largest tumor dimension (LTD) of 2.5 mm and 5 animals reported metastatic disease. Whereas 6 rabbits in the control group developed intraocular tumors, with an average LTD of 5.8 mm and 6 animals reported metastatic disease. The recultured cells from the treated group demonstrated lower proliferation rates and were less invasive (p < 0.001). The PCR array showed differences in expression of genes related to metastasis. Notably, there was 290-fold increase in SERPINB5, a tumor suppressor gene, and a 10-fold higher expression of KISS1, a metastasis suppressor gene, in the treated group. Proangiogenic genes such as VEGFA, PDGFA and PDGFB were downregulated in the treated group. To the best of our knowledge, this is the first report detailing the altered expression of specific genes in UM cells after treatment with IM.

[Pseudotumor cerebri secondary to Behçet disease. Report of one case]. / Pseudotumor cerebri como una manifestación excepcional de la enfermedad de Behçet. Caso clínico.

The classical manifestations of Behçet disease are mouth ana genital ulcers, cutaneous lesions ana ocular involvement. The central nervous system is affected in 5 to 59% of the cases, usually in the form of meningoencephalitis or sinus venous thrombosis. We report a 17-year-old femóle presenting with a two weeks history of progressive headache, nausea and blurred vision. An initial magnetic resonance was normal. Fifteen days later she was admitted to the hospital due to progression of visual impairment. She gave a history of oral ulcers and arthralgias. A new magnetic resonance was normal. A lumbar puncture showed a cerebrospinal fluid with a protein concentration of 14 mg/dl, a glucose concentration of 64 mg/dl, 20 fresh red blood cells and a pressure of 26 cm H(2)0. The diagnosis of a pseudotumor cerebri, secondary to Behçet disease was raised and the patient was treated with colchicine and acetazolamide. The evolution was torpid and an anterior uveitis was also found. After discharge, she continued with oral and genital ulcers and was treated with infliximab. Despite treatment, headache persists.

Pseudotumor cerebri como una manifestación excepcional de la enfermedad de Behçet: caso clínico / Pseudotumor cerebri secondary to Behçet disease: report of one case

The classical manifestations of Behçet disease are mouth ana genital ulcers, cutaneous lesions ana ocular involvement. The central nervous system is affected in 5 to 59 percent of the cases, usually in the form of meningoencephalitis or sinus venous thrombosis. We report a 17-year-old femóle presenting with a two weeks history of progressive headache, nausea and blurred vision. An initial magnetic resonance was normal. Fifteen days later she was admitted to the hospital due to progression of visual impairment. Shegave a history of oral ulcers and arthralgias. A new magnetic resonance was normal. A lumbar puncture showed a cerebrospinal fluid with a protein concentration of 14 mg/dl, aglucose concentration of 64 mg/dl, 20fresh red blood cells and a pressure of 26 cm H(2)0. The diagnosis of a pseudotumor cerebri, secondary to Behçet disease was raised and the patient was treated with colchicine and acetazolamide. The evolution was torpid and an anterior uveitis was alsofound. After discharge, she continued with oral and genital ulcers and was treated with infliximab. Despite treatment, headache persists.

Incidence of melanocytic lesions of the conjunctiva in a review of 10 675 ophthalmic specimens.

During the study period, 10,675 human ophthalmic specimens were received at The Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, McGill University, Montreal, Canada. Of those, 271 were conjunctival lesions (2.5%), with 101 being classified as melanocytic: 50 (49.5%) nevi, 36 (35.6%) primary acquired melanoses, and 15 (14.9%) melanomas. After exclusion of referred cases, 85 lesions were included in the study: 44 (51.7%) nevi, 33 (38.8%) primary acquired melanoses, and 8 (9.4%) melanomas. The most prevalent location was the bulbar conjunctiva. Conjunctival melanomas were most commonly found in an older age group than primary acquired melanosis or nevi. Conjunctival nevi were subdivided into compound (32.9%), subepithelial (16.4%), and junctional (2.3%). Primary acquired melanosis were further classified into primary acquired melanosis with atypia (8.2%) and primary acquired melanosis without atypia (30.5%). Primary acquired melanoses was the predisposing lesion in 75% of the cases of melanoma. In our sample, referral bias could alter the distribution of conjunctival pigmented lesions, with a shift toward the malignant end.

SPARC is expressed in human uveal melanoma and its abrogation reduces tumor cell proliferation.

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) has been shown to play an integral role in the progression of numerous malignancies. The aim of this study was to investigate the expression of SPARC in uveal melanoma (UM). MATERIALS AND METHODS: SPARC expression was assessed in UM cell lines using RT-PCR and immunocytochemistry. Small interfering RNA directed against SPARC was used to transfect each of the cell lines, which were subsequently run in proliferation assays. SPARC expression was further investigated in 19 cases of human UM and 11 primary and 8 metastatic tumors from a rabbit xenograft model. RESULTS: The cell lines transfected with SPARC siRNA showed a significant decrease in proliferation compared to controls. All cases of human uveal melanoma demonstrated positive staining for SPARC as did all primary and metastatic tumors from the xenograft model. CONCLUSION: SPARC may represent a novel target to inhibit growth of UM.

Orbital leiomyoma: histopathologic and immunohistochemical findings of a rare tumor.

A 51-year-old man was referred for evaluation of a right orbital hemangioma. Ophthalmologic examination was unremarkable except for 1 mm of proptosis OD. CT revealed a 10-mm lesion with evidence of growth from 6 to 10 mm within a year. The tumor did not compromise other orbital structures. An excisional biopsy was performed. On the basis of the histopathologic and immunohistochemical findings, the diagnosis of orbital leiomyoma was established. Orbital leiomyoma is a slow-growing tumor that can be located anywhere in the orbit. Posterior tumors are believed to originate from smooth muscle cells of vessel walls; anterior lesions may arise from the capsulopalpebral or Müller muscle. Although there are no unique features that help the radiologist to exclude other benign lesions of the orbit, the histopathologic diagnosis using immunohistochemical markers is usually straightforward. Attention to the cytologic features that exclude the malignant variant is of utmost relevance for proper diagnosis and patient counseling.

Expression of cyclooxygenase-2 in choroidal neovascular membranes from age-related macular degeneration patients.

PURPOSE: The objective of this study was to investigate the expression of cyclooxygenase (COX)-2 in human choroidal neovascular membranes. METHODS: Paraffin-embedded sections of choroidal neovascular membranes excised from 16 patients with wet age-related macular degeneration were used for this study. Sections were subjected to immunohistochemistry using a monoclonal mouse antihuman COX-2 antibody. Staining was classified as either negative or positive in retinal pigment epithelial cells, vascular endothelial cells, and fibroblasts. Serial sections were stained for vimentin expression to confirm tissue antigenicity. RESULTS: Eleven of 16 (69%) choroidal neovascular membranes stained positive for COX-2 in retinal pigment epithelial cells, with 6 (38%) of these also expressing COX-2 in vascular endothelial cells and 6 (38%) in fibroblasts. None of the sections that were negative for COX-2 in the retinal pigment epithelial cells showed COX-2 expression in the other cell types assessed. There was a statistically significant difference (P = 0.0097) in the mean ages between the COX-2 positive group (65.6 years) and COX-2 negative group (76.8 years) as determined by a two-tailed, unpaired Student's t-test. CONCLUSION: The expression of COX-2 in human choroidal neovascular membranes suggests a possible role for this modulator in age-related macular degeneration pathogenesis. The age-dependent expression observed is novel and warrants further investigation.

Anetodermic variant of a periorbital pilomatricoma.

Pilomatricoma usually presents as a solitary hard nodule located deep in the dermis. However, a variant termed anetodermic is often seen in the elderly. Instead of a hard nodule, a rapidly growing bullous lesion is seen. The authors report a 60-year-old man who presented with an erythematous bullous lesion at the left medial canthus. The lesion started as a small 3-mm papule and grew significantly to a 12-mm lesion in 5 weeks. Histopathologically, the tumor was composed of basophilic and keratinized shadow cells typical of pilomatricoma. Anetodermic changes could also be seen, represented by intralesional hemorrhage, dilated blood and lymphatic vessels, and disruption of dermal collagen fibers. The anetodermic variant of pilomatricoma was described in 1943 and accounts for only 2% of cases. Compression of vessels by the neoplastic process and peritumoral inflammatory infiltration are the proposed pathogenic mechanisms underlying the atypical findings.