Extranodal Rosai-Dorfman Disease of the Orbit: Clinical Features of 8 Cases.

PURPOSE: To report on the presentation, radiography, histology, and treatment of 8 cases of extranodal Rosai-Dorfman disease involving the orbit. METHODS: Multicenter retrospective case series. RESULTS: Five males and 3 females had a median age of 10 years (range 2-78 years). Presenting signs and symptoms included proptosis, periorbital pain, palpable mass, blepharoptosis, decreased vision, diplopia, impaired extraocular motility, and afferent pupillary defect. Four patients had bilateral orbital disease, while 4 had unilateral disease. Six cases were extraconal, 1 was intraconal, and 1 was both intra- and extra-conal. Four cases had only extranodal disease without lymphadenopathy (3 of which had localized orbital disease). Diagnosis was confirmed by exam, orbital, and/or systemic radiography, and biopsy in all cases. Treatment strategies included excision or debulking, systemic corticosteroids, chemotherapy, radiotherapy, observation or a combination thereof. At last follow up, 4 patients were disease free, while 4 had residual improved disease. CONCLUSIONS: Rosai-Dorfman disease of the orbit is a rare clinical entity. Purely extranodal disease is rare, with isolated orbital disease being exceedingly rare. This study is unique in that 4 of 8 patients had strictly isolated extranodal disease of the orbit. A large majority of the cases had disease in the extraconal space, contrasting with previous reports. In addition, lacrimal gland disease, particularly bilateral involvement, was prominent in the current study. Although there is no consensus on treatment, surgical excision should be attempted if plausible in symptomatic patients especially if the orbit represents a localized site of disease.

Constitutive and LPS-induced expression of MCP-1 and IL-8 by human uveal melanocytes in vitro and relevant signal pathways.

PURPOSE: Melanocytes are one of the major cellular components in the uvea. Interleukin-8/CXCL8 and monocyte chemoattractant protein-1 (MCP-1/CCL2) are the two most important proinflammatory chemokines. We studied the constitutive and lipopolysaccharide (LPS)-induced expression of IL-8 and MCP-1 in cultured human uveal melanocytes (UM) and explored the relevant signal pathways. METHODS: Conditioned media and cells were collected from UM cultured in medium with and without stimulation of LPS. Interleukin-8 and MCP-1 proteins and mRNAs were measured using an ELISA kit and RT-PCR, respectively. Nuclear factor (NF)-κB in nuclear extracts and phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases1/2 (ERK1/2), and c-Jun N-terminal kinase1/2 (JNK1/2) in cells cultured with and without LPS were measured by ELISA kits. Inhibitors of p38 (SB203580), ERK1/2 (UO1026), JNK1/2 (SP600125), and NF-κB (BAY11-7082) were added to the cultures to evaluate their effects. RESULTS: Low levels of IL-8 and MCP-1 proteins were detected in the conditioned media in UM cultured without serum. Lipopolysaccharide (0.01-1 µg/mL) increased IL-8 and MCP-1 mRNAs and proteins levels in a dose- and time-dependent manner, accompanied by a significant increase of phosphorylated JNK1/2 in cell lysates and NF-κB in nuclear extracts. Nuclear factor-κB and JNK1/2 inhibitors significantly blocked LPS-induced expression of IL-8 and MCP-1. CONCLUSIONS: This is the first report on the expression and secretion of chemokines by UM. The data suggest that UM may play a role in the pathogenesis of ocular inflammatory diseases.

Zeaxanthin Induces Apoptosis in Human Uveal Melanoma Cells through Bcl-2 Family Proteins and Intrinsic Apoptosis Pathway.

The cytotoxic effects of zeaxanthin on two human uveal melanoma cell lines (SP6.5 and C918) and related signaling pathways were studied and compared to effects on normal ocular cells (uveal melanocytes, retinal pigment epithelial cells, and scleral fibroblasts). MTT assay revealed that zeaxanthin reduced the cell viability of melanoma cells in a dose-dependent manner (10, 30, and 100 µ M), with IC50 at 40.8 and 28.7 µ M in SP6.5 and C918 cell lines, respectively. Zeaxanthin did not affect the viability of normal ocular cells even at the highest levels tested (300 µ M), suggesting that zeaxanthin has a selectively cytotoxic effect on melanoma cells. Zeaxanthin induced apoptosis in melanoma cells as indicated by annexin V and ethidium III flow cytometry. Western blot analysis demonstrated that zeaxanthin decreased the expression of antiapoptotic proteins (Bcl-2 and Bcl-xL) and increased the expression of proapoptotic proteins (Bak and Bax) in zeaxanthin-treated melanoma cells. Zeaxanthin increased mitochondrial permeability as determined by JC-1 fluorescein study. Zeaxanthin also increased the level of cytosol cytochrome c and caspase-9 and -3 activities, but not caspase-8, as measured by ELISA assay or colorimetric assay. All of these findings indicate that the intrinsic (mitochondrial) pathway is involved in zeaxanthin-induced apoptosis in uveal melanoma cells.

Detection of herpes simplex virus type 1 in failed descemet stripping automated endothelial keratoplasty grafts.

PURPOSE: To determine the prevalence of herpes simplex virus type 1 (HSV-1) DNA in failed Descemet membrane stripping automated endothelial keratoplasty (DSAEK) grafts. METHODS: A retrospective interventional case series of patients with DSAEK graft failure treated at the New York Eye and Ear Infirmary between January 2009 and July 2012 was performed. Repeat DSAEK, penetrating keratoplasty, or keratoprosthesis procedure was subsequently performed on eyes with failed grafts. All failed grafts were examined immunohistochemically and with qualitative real-time polymerase chain reaction for HSV-1 DNA. In HSV-1-positive cases, corneoscleral donor rims from the original DSAEK procedures were also examined immunohistochemically and with polymerase chain reaction. RESULTS: Fifty-one failed DSAEK grafts from 50 eyes of 49 patients were identified. Indications for DSAEK were pseudophakic bullous keratopathy (28/51, 55%), Fuchs corneal endothelial dystrophy (12/51, 23%), failed penetrating keratoplasty (7/51, 14%), corneal decompensation from glaucoma (2/51, 4%), herpetic endotheliitis (1/51, 2%), and failed DSAEK (1/51, 2%). Forty-three grafts (83%) were primary DSAEK graft failure. HSV-1 DNA was isolated from 2 of 51 failed DSAEK grafts (4.0%). The corresponding corneoscleral donor rims did not demonstrate the presence of HSV-1. CONCLUSIONS: Based on our results, HSV-1 infection plays a minor role in DSAEK graft failure. The data suggest that recipient reactivation, rather than donor transmission, plays a role in HSV infection.

The molecular genetics of eyelid tumors: recent advances and future directions.

BACKGROUND: Unprecedented recent advances in the molecular genetics of cutaneous malignancies have markedly improved our ability to diagnose, treat, and counsel patients with skin tumors. This review provides an update on molecular genetics of periocular cutaneous basal cell carcinoma, squamous cell carcinoma, sebaceous carcinoma, Merkel cell carcinoma, and malignant melanoma and describes how the knowledge of molecular genetics is translated into clinical practice. METHODS: A literature search of peer-reviewed and indexed publications from 1965 to 2012 using the PubMed search engine was performed. Key terms included: molecular genetics, eyelid, basal cell carcinoma, squamous cell carcinoma, sebaceous adenoma, sebaceous epithelioma, sebaceoma, sebaceous carcinoma, Merkel cell carcinoma, and melanoma. Seminal articles prior to 1965 were selected from primary sources and reviews from the initial search. Articles were chosen based on pertinence to clinical, genetic, and therapeutic topics reviewed in this manuscript. RESULTS: We reviewed the literature regarding the advances in molecular genetics of cutaneous basal cell carcinoma, squamous cell carcinoma, sebaceous neoplasia, Merkel cell carcinoma, and malignant melanoma, and possible future directions towards diagnosing and treating cutaneous tumors at the genetic level. Cell culture experiments, animal models, and molecular genetic studies on the patients' tumor tissues helped to elucidate genetic aberrations in these lesions. Cell culture experiments, animal studies and, ultimately, clinical trials provided means to test and develop novel therapeutic strategies, namely targeted therapy directed at specific molecular genetic defects. While remarkable progress has been made in this process, the complexity of the molecular genetics of skin tumors makes complete elucidation of the genetic mechanisms and the search for ideal therapies challenging. CONCLUSIONS: The recent studies focusing on molecular genetics of cutaneous malignancies show promising results, thereby improving our ability to diagnose, treat and counsel patients with these lesions. Future studies will hopefully help unravel further molecular mechanisms involved in cutaneous neoplasia and provide insights into novel preventative and therapeutic modalities.

Infected epithelial inclusion cyst simulating conjunctival melanoma.

There are several pigmented nonneoplastic lesions that can clinically simulate melanocytic tumors. The authors report an unusual conjunctival epithelial inclusion cyst that contained luminal bacterial colonies, hemorrhage, and epithelial debris. Clinical appearance convincingly simulated a melanoma. The clinical and histopathologic features of this lesion are discussed.

Intraocular schwannoma.

Schwannoma is a proliferation of neoplastic Schwann cells. Whereas schwannomas of the head and neck region are common, intraocular tissues are rarely affected. Uveal schwannoma has been aptly called a "pseudomelanoma", reflecting the difficulty in its clinical distinction from uveal malignant melanoma. Most of our current knowledge on intraocular schwannoma is limited to case reports, short case series, and non-comprehensive literature reviews. Three isolated reports of uveal schwannoma with extrascleral extension exist in literature, but the prognostic significance of this growth pattern is unknown. We present a patient with choroidal schwannoma with extrascleral extension and review 46 previously reported cases of uveal schwannomas to delineate clinical and pathologic characteristics of these intraocular tumors with a specific emphasis on schwannoma with extraocular extension.

Mucin-producing sweat gland carcinoma of the eyelid: diagnostic and prognostic considerations.

PURPOSE: To describe the clinical and pathologic characteristics of mucin-producing sweat gland carcinoma of the eyelid and to determine whether neuroendocrine differentiation is of prognostic significance. DESIGN: Retrospective interventional case series. METHODS: Search of the New York Eye and Ear Infirmary pathology database between 1990 and 2011 identified 16 patients with mucin-producing sweat gland carcinoma. Clinical, histopathologic, and immunohistochemical analyses were performed on all identified cases. RESULTS: The patients presented with vascularized, focally cystic, nonulcerated eyelid margin lesions. Histopathologic evaluation showed that 4 lesions (25%) had a cystic, papillary, and solid growth pattern with an in situ component, 7 (44%) were pure invasive mucinous carcinomas, and 5 (31%) demonstrated both growth patterns. Immunohistochemical analysis of 15 tumors showed that pure cystic/papillary lesions had a significantly greater percentage of synaptophysin-immunoreactive cells (P = .036). There was no significant difference in the number of neuroendocrine markers expressed or in the intensity of immunostaining among the 3 different growth patterns. Re-excision for margin clearance was performed in 8 of 13 cases (61.5%). Two of 13 lesions recurred (15%); 1 of these was an in situ tumor with cystic morphology and neuroendocrine differentiation and the other was pure invasive mucinous carcinoma. None of the lesions metastasized. CONCLUSIONS: Mucin-producing sweat gland carcinoma pathologically represents a continuum, from an in situ lesion to a classic, invasive mucinous carcinoma. Immunohistochemical evidence of neuroendocrine differentiation can be observed in all lesions and does not appear to have a prognostic significance, arguing against the utility of immunohistochemical subtyping of mucinous sweat gland carcinomas.

Effects of melatonin and its receptor antagonist on retinal pigment epithelial cells against hydrogen peroxide damage.

PURPOSE: Recently, we reported finding that circulating melatonin levels in age-related macular degeneration patients were significantly lower than those in age-matched controls. The purpose of this study was to investigate the hypothesis that melatonin deficiency may play a role in the oxidative damage of the retinal pigment epithelium (RPE) by testing the protective effect of melatonin and its receptor antagonist on RPE cells exposed to H(2)O(2) damage. METHODS: Cultured human RPE cells were subjected to oxidative stress induced by 0.5 mM H(2)O(2). Cell viability was measured using the microculture tetrazoline test (MTT) assay. Cells were pretreated with or without melatonin for 24 h. Luzindole (50 µM), a melatonin membrane-receptor antagonist, was added to the culture 1 h before melatonin to distinguish direct antioxidant effects from indirect receptor-dependent effects. All tests were performed in triplicate. RESULTS: H(2)O(2) at 0.5 mM decreased cell viability to 20% of control levels. Melatonin showed dose-dependent protective effects on RPE cells against H(2)O(2). Cell viability of RPE cells pretreated with 10(-10), 10(-8), 10(-6), and 10(-4) M melatonin for 24 h was 130%, 160%, 187%, and 230% of cells treated with H(2)O(2) alone (all p<0.05). Using cells cultured without H(2)O(2) as the control, cell viability of cells treated with H(2)O(2) after pretreatment with 10(-10)-10(-4) M melatonin was still significantly lower than that of the controls, suggesting that melatonin significantly decreased but did not completely abolish the in vitro cytotoxic effects of H(2)O(2). Luzindole completely blocked melatonin's protective effects at low concentrations of melatonin (10(-10)-10(-8) M) but not at high concentrations (10(-6)-10(-4) M). CONCLUSIONS: Melatonin has a partial protective effect on RPE cells against H(2)O(2) damage across a wide range of concentrations (10(-10)-10(-4) M). This protective effect occurs through the activation of melatonin membrane receptors at low concentrations (10(-10)-10(-8) M) and through both the direct antioxidant and indirect receptor activation effects at high concentrations (10(-6)-10(-4) M).

Butein induces apoptosis in human uveal melanoma cells through mitochondrial apoptosis pathway.

PURPOSE: To study the cytotoxic effects and related signaling pathways of butein on human uveal melanoma cells in vitro. MATERIALS AND METHODS: Three human uveal melanoma cell lines (M17, SP6.5, and C918), retinal pigment epithelial (RPE) cells and scleral fibroblasts were treated with butein at different dosages. The effects of butein on cell viability were assessed by using the MTT assay. Cell apoptosis was determined using annexin V-FITC/ethidium homodimer III flow cytometry. Mitochondrial transmembrane potential changes were assessed by using the JC-1 fluorescent reader, cytosol cytochrome c levels, and the activities of caspase-3, -8, and -9 were measured by using an enzyme-linked immunosorbent assay or colorimetric assay. RESULTS: Butein reduced the cell viability of cultured human uveal melanoma cells in a dose-dependent manner (10, 30, and 100 µM), with IC50 at 13.3 µM and 15.8 µM in SP6.5 and M17 cell lines, respectively. Similar effects were also found in a highly aggressive and metastatic C918 cell line (IC50 16.7 µM). Butein at lower concentrations (10-30 µM) selectively reduced the cell viability of uveal melanoma cells, without affecting cell viability of RPE cells and fibroblasts. Butein-induced apoptosis of melanoma cells, increased mitochondrial permeability and the level of cytosol cytochrome c, caspase-9 and -3 activities (but not caspase-8) in a dose-dependent manner. CONCLUSIONS: Butein has selectively potent pro-apoptotic effects on cultured human uveal melanoma cells via the intrinsic mitochondrial pathway.

Expression of neurotrophin receptors by retinoinvasive uveal melanoma.

Retinoinvasive uveal melanoma demonstrates prominent diffuse retinal and optic nerve invasion, with little or no involvement of the adjacent choroid. Prior studies have advanced hypotheses on the potential role of molecular and cellular interactions in the pathogenesis of retinoinvasiveness and neuroinvasiveness, but the precise molecular events are not known. Here, we investigate the role of neutrotrophic factors in the pathogenesis of retinoinvasive uveal melanoma. The records of three ophthalmic pathology departments (The New York Eye and Ear Infirmary, Wills Eye Institute, and University of California San Francisco) were searched to identify all cases of retinoinvasive uveal melanoma, yielding four eyes (all previously irradiated). Eight eyes with nonretinoinvasive melanomas (four irradiated and four nonirradiated) were randomly selected as controls. All enucleated eyes were examined histopathologically and immunohistochemically for the expression of neurotrophic factor receptors [Pan-Trk, p75 neurotrophin receptor (p75(NTR) and ciliary neurotrophic factor receptor-α]. Histopathologic features were similar in both retinoinvasive and control melanomas with regard to choroidal tumor location and size, neovascular glaucoma, and cell type. The eyes with retinoinvasive melanoma showed diffuse retinal invasion beyond the choroidal tumor (n=4) and prelaminar (n=1) and retrolaminar (n=2) optic nerve invasion. The control melanomas showed focal retinal invasion over the tumor apices (n=6) and prelaminar optic nerve invasion (n=1). Nonirradiated melanomas demonstrated no trace immunoreactivity for neurotrophic factor receptors, whereas irradiated melanomas showed more prominent (trace to moderate) immunoreactivity. When controlled for irradiation, no difference in immunoreactivity for neurotrophin receptors nor tumor duration was observed between retinoinvasive and nonretinoinvasive melanomas. This study failed to demonstrate a direct causation between the expression of neurotrophin receptors and a retinoinvasive uveal melanoma growth pattern.

Syringocystadenocarcinoma papilliferum of the eyelid.

An 86-year-old man presented with an ulcerated, painless right lower eyelid lesion of unknown duration. Excisional biopsy was performed to rule out suspected basal cell carcinoma. Pathologic evaluation demonstrated syringocystadenocarcinoma papilliferum. Three months after complete excision of the tumor, the patient remains well with no evidence of local recurrence or metastases. Review of the literature identified 20 cases of syringocystadenocarcinoma papilliferum, none of which presented in the skin of the ocular adnexa. The authors review the typical presentation, clinical course, and outcome of patients with syringocystadenocarcinoma papilliferum and compare these data to the case presented here.

Induction of dermal collagenesis, angiogenesis, and adipogenesis in human skin by injection of platelet-rich fibrin matrix.

OBJECTIVE: To evaluate the histological changes induced in human skin by injection of autologous platelet-rich fibrin matrix (PRFM). METHODS: Four healthy adult volunteers were included in the study. Platelet-rich fibrin matrix was prepared from 9 mL of autologous blood using a proprietary system (Selphyl; Aesthetic Factors, Wayne, New Jersey) and injected into the deep dermis and immediate subdermis of the upper arms of subjects. Full-thickness skin biopsy specimens were taken from the treated areas over a 10-week period, and the specimens were processed for histological evaluation. RESULTS: Findings from histological examination supported the clinical observation of soft-tissue augmentation. As early as 7 days after treatment, activated fibroblasts and new collagen deposition were noted and continued to be evident throughout the course of the study. Development of new blood vessels was noted by 19 days; also at this time, intradermal collections of adipocytes and stimulation of subdermal adipocytes were noted. These findings became more pronounced over the duration of the study, although the fibroblastic response became much less pronounced. No abnormal mitotic figures were observed at any point, and a very mild chronic inflammatory response was noted only at the earliest time points of the study. CONCLUSIONS: Injection of PRFM into the deep dermis and subdermis of the skin stimulates a number of cellular changes that can be harnessed for use. Coupled with prior in vitro and in vivo studies, we now have a much clearer picture of the cellular effects of PRFM and its potential uses in facial plastic surgery. Further work is planned to more clearly elucidate the potential role of PRFM in aesthetic and reconstructive surgery.

Plasmacytoma associated with canaliculitis.

Plasmacytomas are plasma cell neoplasms that rarely involve ocular adnexal tissues as a primary lesion or secondary manifestation of plasma cell myeloma. Only one case of plasmacytoma involving the lacrimal drainage system, to our knowledge, is described in the literature. The clinical presentation of ocular adnexal primary plasmacytoma typically relates to its mass effect. In this clinicopathologic report, we describe an unusual presentation of primary plasmacytoma of the lacrimal canaliculus as infectious canaliculitis.

Progressive growth in epibulbar complex choristomas: report of 2 cases and review of literature.

PURPOSE: To report 2 patients with progressive complex choristomas and to review the literature on this subject. DESIGN: Interventional case reports. METHODS: Clinical and pathologic correlation was performed on 2 patients with progressive epibulbar choristomas. PubMed database was searched to identify all the previously reported cases of progressive epibulbar choristomas (using key words choristoma, dermoid, growth, progression, and evolution). RESULTS: Growth of the epibulbar choristomas was noted in infancy in 1 patient with oculoectodermal syndrome and in puberty in another otherwise healthy patient. Both lesions were identified histopathologically as complex choristomas. In addition to the characteristic choristomatous tissues, both lesions demonstrated increased vascularity, inflammatory infiltrate, and fibroblast proliferation within myxomatous stroma. Review of the literature identified 4 patients with progressive complex choristomas, 1 of whom demonstrated histopathologic findings similar to those of the 2 cases reported here. CONCLUSIONS: Epibulbar choristomas rarely enlarge, likely secondary to reactive changes within the tissue manifested by increased vascularity, inflammatory cell infiltration, and fibroblast proliferation with deposition of myxomatous stroma.

Isolated Nocardia exalbida endogenous endophthalmitis.

PURPOSE: To report an immunocompetent patient with Nocardia exalbida endogenous endophthalmitis. DESIGN: Case report. METHODS: Clinical-pathologic correlation and microbiologic evaluation were performed on an enucleated eye. RESULTS: A 56-year-old man presented with rapidly progressive vision loss associated with a posterior choroidal mass and serous retinal detachment. Pathologic evaluation of the enucleated eye demonstrated endogenous endophthalmitis. Nocardia exalbida was identified microbiologically. Systemic workup failed to demonstrate definite foci of systemic infection or evidence of immunocompromise. Review of literature failed to identify previously reported cases of Nocardia exalbida endophthalmitis. CONCLUSIONS: Nocardia can rarely cause isolated endogenous endophthalmitis in immunocompetent patients, which can contribute to a delay in diagnosis and vision loss. Endogenous Nocardia endophthalmitis typically occurs in immunocompromised patients with disseminated nocardiosis. Isolated endogenous Nocardia endophthalmitis in immunocompetent patients is rare. We describe isolated endogenous intraocular infection caused by Nocardia exalbida, a novel species, not previously associated with endophthalmitis.

Anterior segment tumor aspiration cutter-assisted biopsy: experience with pathology.

PURPOSE: To report pathologic evaluation and diagnostic yield of an aspiration cutter-assisted biopsy of anterior segment tumors. DESIGN: Retrospective, consecutive, interventional case series. METHODS: Fifty-five eyes of 55 patients with iris and iridociliary tumors underwent an aspiration cutter-assisted biopsy at a single institution. Cytospin and cell-block preparations were performed on all biopsy samples. Bleached preparations and a panel of immunohistochemical stains were performed in selected cases. Cytologic diagnosis was correlated with clinical diagnosis and with histopathologic diagnosis, when available. Main outcome measures were (1) specimen cellularity, (2) diagnostic studies performed, (3) cytopathologic diagnosis, and (4) concordance with histopathologic diagnosis. RESULTS: Specimen cellularity was adequate for cytopathologic interpretation of cytospin preparations in 55 (98.2%) of 56 biopsies. Twenty-three (41%) of 56 biopsy samples had diagnostic material in cell-block preparations. The most common cytopathologic diagnoses were melanoma (n = 39/56; 69.6%), melanocytoma (n = 4/56; 7.1%), nevus (n = 4/56; 7.1%), lymphoma (n = 2/56; 3.6%), and epithelial implantation cyst (n = 2/56; 3.6%). One biopsy sample (1.8%) yielded nondiagnostic material. Wide incisional or excisional biopsy confirmation was available in 13 (23.2%) of 56 aspiration cutter-assisted biopsy cases. Cytopathologic diagnoses were consistent with histopathologic diagnosis in 12 (92.3%) of 13 cases. CONCLUSIONS: Although specialized pathologic techniques were necessary to maximize material available for diagnosis, all biopsies yielded cellular material and 41% yielded diagnostic tissue in cell block preparation. Although lower than the yield of wide incisional or excisional biopsy, aspiration cutter-assisted biopsy of anterior segment tumors achieved a diagnostic yield of 98.2%.

Taut internal limiting membrane causing diffuse diabetic macular edema after vitrectomy: clinicopathological correlation.

AIMS: To describe 2 cases of diffuse diabetic macular edema (DME) after diabetic vitrectomy caused by a taut internal limiting membrane (ILM), with clinicopathological correlation. METHODS: Interventional case series with immunohistochemical analysis. RESULTS: Two patients were referred for unresponsive diffuse DME after pars plana vitrectomy with removal of the posterior hyaloid. Clinically, a taut ILM was noted over the fovea, and its removal resulted in rapid and long-term resolution of the edema, confirmed by optical coherence tomography with visual acuity improvement. Histopathology with immunostaining revealed a segment of ILM with an inner monolayer of cytokeratin-positive (retinal pigment epithelial cells) and/or glial fibrillary acidic protein-positive cells with smooth muscle actin immunoreactivity. CONCLUSIONS: A taut ILM can cause diffuse DME after vitrectomy, and its removal can restore the normal foveal contour and improve visual acuity. Tangential tractional forces from contractile cells propagated across the fovea via the ILM appear to be the etiology.

Progress in the studies of etiology, epidemiology and pathogenesis of ocular melanomas.

Our population-based epidemiological studies demonstrated that the epidemiological aspects of ocular melanomas are different from those in cutaneous melanoma. The incidences of conjunctival melanoma increased in the past decades and was higher in the South (greater sun exposure), which is consistent with the occurrence of cutaneous melanoma. On the contrary, incidences of uveal melanoma are in the opposite direction of cutaneous melanomas. This indicates that solar radiation does not cause an increase of incidences of melanoma in ocular tissues (uveal melanoma) that are not exposed to solar radiation. Solar radiation increases the incidence of melanoma only in tissues exposed to said radiation, such as in conjunctival and eyelid melanomas. Uveal melanoma incidences in light-pigmented individuals are much greater than in dark-pigmented individuals. This result cannot be attributed to a melanin photo-screening effect, and is possibly related to melanin's biophysical and biochemical effects. The difference in incidences between light- and dark-pigmented individuals in conjunctival melanomas, as well as in vulvar and vaginal melanomas, are much lower than that in the uveal and cutaneous melanomas. This difference may be related to the different histological structures in these melanomas; conjunctival and vaginal melanomas occur in the mucous membrane, whereas cutaneous melanomas occur in the skin. Recent molecular biological studies indicate that each type of melanoma has its own molecular changes which are different from the others. Therefore, independent studies are required for each type of melanoma to discover their own etiology and pathogenesis, and to develop relevant novel prevention and treatment procedures.

Interleukin-1beta increases baseline expression and secretion of interleukin-6 by human uveal melanocytes in vitro via the p38 MAPK/NF-kappaB pathway.

PURPOSE: Melanocyte is the major cell component in the uvea. Interleukin (IL)-6 is a proinflammatory cytokine. The authors studied the expression of IL-6 in cultured human uveal melanocytes (UMs) and their modulation by IL-1ß and explored the relevant signal pathways. METHODS: Conditioned media and cells were collected from UMs cultured in medium with and without serum and were stimulated by IL-1ß. IL-6 protein and transcript were measured using an ELISA kit and RT-PCR, respectively. NF-κB in nuclear extracts and phosphorylated p38 MAPK, ERK, and JNK in cells cultured with and without IL-1ß were measured by ELISA kits. Inhibitors of p38 (SB203580), ERK (UO1026), JNK (SP600125), and NF-κB (BAY11-7082) were added to the cultures to evaluate their effects. RESULTS: Low levels of IL-6 protein were detected in the conditioned medium in UMs cultured without serum. The addition of serum increased the secretion of IL-6. IL-1ß (0.1-10 ng/mL) increased IL-6 transcript and protein levels in a dose- and time-dependent manner up to sixfold, accompanied by a significant increase of NF-κB in nuclear extracts and phosphorylated p38 MAPK in cell lysates. NF-κB and p38 inhibitors alone decreased, whereas a combination of these two inhibitors completely abolished the IL-1ß-induced expression of IL-6. CONCLUSIONS: This is the first report on the expression and secretion of IL-6 by UMs. IL-1ß augments IL-6 production from the melanocytes. The data suggest that UMs may play a role in the pathogenesis of ocular inflammatory and autoimmune diseases.