A Polysomnographic Study of Effects of Sleep Deprivation on Novice and Senior Surgeons during Simulated Vitreoretinal Surgery.

PURPOSE: To assess the impact of a 3-hour polysomnography (PSG)-recorded night of sleep deprivation on next-morning simulated microsurgical skills among vitreoretinal (VR) surgeons with different levels of surgical experience and associate the sleep parameters obtained by PSG with Eyesi-generated performance. DESIGN: Self-controlled cohort study. PARTICIPANTS: Eleven junior VR surgery fellows with < 2 years of surgical experience and 11 senior surgeons with > 10 years of surgical practice. METHODS: Surgical performance was assessed at 7am after a 3-hour sleep-deprived night using the Eyesi simulator and compared with each subject's baseline performance. MAIN OUTCOME MEASURES: Changes in Eyesi-generated score (0-700, worst to best), time for task completion (minutes), tremor-specific score (0-100, worst to best), and out-of-tolerance tremor percentage. Polysomnography was recorded during sleep deprivation. RESULTS: Novice surgeons had worse simulated surgical performance after sleep deprivation compared with self-controlled baseline dexterity in the total score (559.1 ± 39.3 vs. 593.8 ± 31.7; P = 0.041), time for task completion (13.59 ± 3.87 minutes vs. 10.96 ± 1.95 minutes; P = 0.027), tremor-specific score (53.8 ± 19.7 vs. 70.0 ± 15.3; P = 0.031), and out-of-tolerance tremor (37.7% ± 11.9% vs. 28.0% ± 9.2%; P = 0.031), whereas no performance differences were detected in those parameters among the senior surgeons before and after sleep deprivation (P ≥ 0.05). Time for task completion increased by 26% (P = 0.048) in the post-sleep deprivation simulation sessions for all participants with a high apnea-hypopnea index (AHI) and by 37% (P = 0.008) among surgeons with fragmented sleep compared with those with normal AHI and < 10 arousals per hour, respectively. Fragmented sleep was the only polysomnographic parameter associated with a worse Eyesi-generated score, with a 10% (P = 0.005) decrease the following morning. CONCLUSIONS: This study detected impaired simulated surgical dexterity among novice surgeons after acute sleep deprivation, whereas senior surgeons maintained their surgical performance, suggesting that the impact of poor sleep quality on surgical skills is offset by increased experience. When considering the 2 study groups together, sleep fragmentation and AHI were associated with jeopardized surgical performance after sleep deprivation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH RETINAL PIGMENT EPITHELIAL TEAR IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To report a patient presenting a retinal pigment epithelial tear in which optical coherence tomography angiography enabled the visualization of subfoveal choroidal neovascularization (CNV) not evidenced by the fluorescein angiography. She was treated with 3 monthly intravitreous anti-VEGF injections and intraretinal fluid resolution occurred. METHODS: Observational case report. RESULTS: A 62-year-old Caucasian woman presented with decreased visual acuity in the right eye for 3 months. Fundus biomicroscopy revealed a yellowish macular lesion associated with intraretinal hemorrhage. Fluorescein angiography showed a large hyperfluorescent area consistent with window defect. Optical coherence tomography showed a retinal pigment epithelial tear with subretinal fluid. However, there was no clear evidence of CNV on fluorescein angiography or OCT. Optical coherence tomography angiography confirmed the presence of an active CNV by the visualization of the neovascular network in the region corresponding to the scrolled up retinal pigment epithelium. CONCLUSION: This case report demonstrates that optical coherence tomography angiography can be useful to confirm the presence of CNV in cases where fluorescein angiography and OCT cannot establish the diagnosis. The reported case suggests the applicability of optical coherence tomography angiography in patients in whom retinal pigment epithelial tear is detected and associated CNV is suspected.

Optical coherence tomography angiography artifactual choroidal neovascularization in optic disc pit maculopathy.

This case report describes a 19-year-old Caucasian man presented with decreased visual acuity in the right eye for 3 months. Dilated funds exam revealed optic disk pit associated with serous macular detachment. Optical coherence tomography identified communication between the optic disk pit and the macular serous detachment, and optical coherence tomography angiography displayed a subfoveal area suggestive of subfoveal choroidal neovascularization. However, there was no evidence of leakage in the fluorescein angiogram and no evidence of choroidal neovascularization in optical coherence tomography in the area corresponding to the suspicious subfoveal choroidal neovascularization. The patient underwent 23-gauge pars plana vitrectomy in the right eye. Six weeks after surgery, multimodal imaging was repeated and there was near-complete resorption of the subretinal fluid. Optical coherence tomography angiography signal superimposed on optical coherence tomography B-scan also demonstrated normal choriocapillaris signal throughout the macula. In conclusion, optical coherence tomography angiography may produce artifacts in optic disk pit maculopathy that simulate choroidal neovascularization.

Optical coherence tomography angiography artifactual choroidal neovascularization in optic disc pit maculopathy / Artefato de neovascularização de coroide na angiografia por tomografia de coerência óptica em pit de disco óptico

ABSTRACT This case report describes a 19-year-old Caucasian man presented with decreased visual acuity in the right eye for 3 months. Dilated funds exam revealed optic disk pit associated with serous macular detachment. Optical coherence tomography identified communication between the optic disk pit and the macular serous detachment, and optical coherence tomography angiography displayed a subfoveal area suggestive of subfoveal choroidal neovascularization. However, there was no evidence of leakage in the fluorescein angiogram and no evidence of choroidal neovascularization in optical coherence tomography in the area corresponding to the suspicious subfoveal choroidal neovascularization. The patient underwent 23-gauge pars plana vitrectomy in the right eye. Six weeks after surgery, multimodal imaging was repeated and there was near-complete resorption of the subretinal fluid. Optical coherence tomography angiography signal superimposed on optical coherence tomography B-scan also demonstrated normal choriocapillaris signal throughout the macula. In conclusion, optical coherence tomography angiography may produce artifacts in optic disk pit maculopathy that simulate choroidal neovascularization.

RESUMO O presente estudo relatou o caso de um homem caucasiano de 19 anos com diminuição da acuidade visual no olho direito há 3 meses. Na fundoscopia havia um pit de papila associado ao descolamento seroso macular. A tomografia de coerência óptica identificou uma comunicação entre o pit e o descolamento seroso e a angiografia por tomografia de coerência óptica demonstrou uma área subfoveal sugestiva de membrana neovascular sub-retiniana. No entanto, não houve evidência de vazamento na angiofluoresceínografia com contraste e nem de membrana neovascular sub-retiniana na tomografia de coerência óptica na área suspeita. O paciente foi submetido a vitrectomia pars plana 23-gauge no olho direito. Seis semanas após a cirurgia, os exames foram repetidos e houve reabsorção quase completa do líquido sub-retiniano. O sinal da angiografia por tomografia de coerência óptica sobreposto à tomografia de coerência óptica B-scan era normal na região da mácula. Em conclusão, a angiografia por tomografia de coerência óptica pode produzir artefatos em maculopatia secundária a pit de papila que simulam uma membrana neovascular sub-retiniana.

Acute retinal necrosis and immune reconstitution inflammatory syndrome in a natalizumab-treated patient with multiple sclerosis.

PURPOSE: To describe a case of acute retinal necrosis and subsequent immune reconstitution inflammatory syndrome in a patient with multiple sclerosis treated with natalizumab. METHODS: Case report. RESULTS: A 51-year-old man with multiple sclerosis developed acute retinal necrosis during treatment with natalizumab. The patient was successfully managed with natalizumab discontinuation, oral valacyclovir, and prophylactic laser retinal photocoagulation. A few months after natalizumab interruption and 1 month after valacyclovir completion, the patient presented with an episode of presumed noninfectious anterior and intermediate uveitis, which responded well to oral steroid mini-pulse therapy. CONCLUSION: Natalizumab is a potent immune suppressor used in the treatment of multiple sclerosis and Crohn disease. It has already been linked to herpetic infections and immune reconstitution inflammatory syndrome in the central nervous system. These complications may also affect ocular tissues.

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.

Malignancy in the blind painful eye--report of two cases and literature review.

BACKGROUND: Few cases of malignant tumors arising in a blind painful eye have previously been described. We described two cases of a blind painful eye containing an unsuspected tumor, which were enucleated to relieve the pain. CASE PRESENTATIONS: Case 1: A 57 year-old Caucasian man presented with recurrent orbital cellulitis and endophthalmitis in the left eye (OS). The OS was blind and painful and an enucleation was performed showing a uveal melanoma by histopathological exam. Case 2: A 54 year-old Caucasian man with previous history of a rhegmatogenous retinal detachment in his left eye presented a blind painful eye. Enucleation was performed revealing a well-differentiated B-cell lymphoma of uveal tract with extra ocular extension. CONCLUSION: In the management of a blind painful eye, it is extremely important to rule out an intraocular malignancy particularly in those patients who have not been followed by an ophthalmologist.

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.

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.

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.

Longterm follow-up of patients with multifocal choroiditis and panuveitis.

PURPOSE: To report the visual prognosis and longterm complications in patients with multifocal choroiditis and panuveitis (MCP). METHODS: A retrospective study was performed with patients who met inclusion criteria for MCP at the Uveitis Clinic, Royal Victoria Hospital, McGill University, Montreal, Canada. Information collected included duration of follow-up, visual acuity (VA) measured at each clinical visit, ocular and systemic treatment and ocular complications observed during follow-up. RESULTS: Nineteen patients (37 eyes) with MCP with a mean follow-up of 76.9 months were studied. Kaplan-Meier survival analysis showed a decrease in the proportion of patients with a final VA > or = 20/40 over time. Cystoid macular oedema was seen in 29.7% of the eyes and was the most frequent macular abnormality observed in our group. On the other hand, choroidal neovascularization was detected in only six (16.2%) of the eyes, but was related to VA < 20/200 in four of these eyes. Glaucoma was detected in 10.8% of the eyes. Cataract (posterior subcapsular and/or nuclear) was the most common longterm complication, occurring in 40% of affected eyes. Cataract surgery improved the VA in 83.3% of these eyes. CONCLUSION: The visual acuity of patients with MCP decreases with time. Visual loss can occur from complications following the inflammation itself and/or iatrogenic induced by the chronic use of corticosteroids.

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 x 10(-6) M and 1.69 x 10(-6) M, respectively. The IC50 and GI50 concentrations to cell line OCM-1 were 3.69 x 10(-6) M and 2.12 x 10(-6) M, respectively. Previous studies using the same methodology have revealed violacein to have a GI50 in the range (3-6) x 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.

Secretion of interleukin-6 and prostaglandin E2 during uveal melanoma-monocyte in vitro interactions.

Host-tumor interactions in uveal melanoma are not well understood. It is believed that the cytokine interleukin-6 and the lipid mediator autacoid prostaglandin E2 are involved in tumor growth, proliferation, tumor cell survival, and angiogenesis. These cytokines have been shown to be poor prognostic markers in uveal and cutaneous melanoma. In this study, we investigated the levels of interleukin-6 and prostaglandin E2 in monocyte and uveal melanoma conditioned medium. Five human uveal melanoma cell lines (92.1, MKT-BR, OCM-1, SP6.5 and UW-1), and one monocyte cell line (28SC) were seeded in 6 well plates at a concentration of 1 x 10(6)cells ml(-1). After 18 hr melanoma conditioned medium was placed on the monocyte cell line and monocyte conditioned medium was placed on each uveal melanoma cell line. Tumor cells and monocytes incubated in fresh medium after 18 hr were used as controls. Interleukin-6 and prostaglandin E2 levels were determined by immunoassays prior to media transfer and 6, 12, 24, and 36 hr thereafter. In the absence of conditioned medium, neither product showed baseline levels of expression. Interleukin-6 but not prostaglandin E2, which remained undetectable for the duration of the study, showed up-regulation of expression after incubation in conditioned medium. 28SC incubated in melanoma conditioned medium expressed higher levels of interleukin-6 than did uveal melanoma cells incubated in monocyte conditioned medium. In addition each cell line exhibited a distinct pattern of expression with individual cell lines exhibiting peak levels of cytokine production at different time points. The results of this study offer insight into the mechanism by which interleukin 6 may be involved in tumor-host interactions potentially favoring tumor growth, survival, and proliferation.

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.

New prognostic factors in uveal melanomas: potential molecular targets for therapy.

Even with advances in the diagnosis and local treatment of uveal melanoma, there has been no significant change in the survival rates of these patients in the last decades. Metastatic disease still occurs at the same frequency, and no systemic therapy is currently offered to patients after local eye treatment. Therefore, experimental and clinical research has been focused on the metastatic cascade in order to elucidate its underlying mechanisms at the molecular level. As a result, new prognostic factors in uveal melanoma have been described that also serve as molecular targets for the development of novel treatments. These prognostic factors/molecular targets, such as membrane receptors, enzymes, cytokines, cytoskeleton components, oncogenes, tumour suppressor genes, cell-cycle proteins and nuclear antigens, are reviewed in this article.

Macrophage-derived soluble factor enhances melanoma inhibitory activity expression by uveal melanoma cells in vitro.

Melanoma inhibitory activity (MIA) is correlated with tumour progression and development of metastatic disease. Melanoma inhibitory activity, secreted by melanoma cells, is known to inhibit tumour cell attachment to the extracellular matrix enhancing their invasive potential. The regulatory pathways that lead to MIA expression have not yet been elucidated. It is well established that tumour cells and macrophages interact through soluble factors, preventing or enhancing tumour growth. The purpose of the present study was to determine whether soluble factor(s) derived from macrophages lead to the up-regulation of MIA production by human uveal melanoma cell lines (HUMCL) and whether MIA contributes to an increase in the invasive behaviour of HUMCL in vitro. Baseline MIA levels were measured by enzyme-linked immunosorbent assay in five HUMCL of known metastatic potential (92.1>SP6.5>OCM-1>MKT-BR>UW-1). Macrophage conditioned medium (MaCM) was placed on top of the HUMCL and MIA levels were measured at 6, 12, 24, and 36 h. The HUMCL were also seeded in a Matrigel chamber for 72 h and then cells invading the Matrigel were counted. The assay was repeated adding recombinant human MIA to the top layer of each well. All HUMCL expressed MIA at baseline (average of 31 ng/ml at 36 h). Following exposure to MaCM, MIA levels increased to an average of 45.2 ng/ml, with the 92.1 and SP6.5 cell lines expressing the highest MIA levels and UW-1 cell line expressing the lowest level. During the baseline invasion assay, the vast majority of cells (>95%) were found to adhere to the upper surface of the Matrigel. When MIA was added to the invasion chamber, no adhesion or invasion was observed. The results suggest, for the first time, that macrophages secrete a soluble factor(s) that may stimulate nearby melanoma cells to enhance their production of MIA in vitro. Furthermore, increased MIA production may, in turn, increase the invasive properties of the cells by modulating the attachment of HUMCL to the extracellular matrix.

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.