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Temporal artery biopsy is considered the gold standard for the diagnosis of temporal arteritis (TA). However, complications following this procedure may occur. The goal of this study is to evaluate if ultrasound biomicroscope (UBM) findings are useful in predicting the result (positive or negative) of temporal artery biopsy in patients with TA.Twenty-six consecutive patients with clinical diagnosis of TA seen at the Department of Ophthalmology, Royal Victoria Hospital, Montreal, Canada, were involved in this study. All patients were submitted to UBM before temporal artery biopsy. Eight patients presented histopathologic findings consistent with the diagnosis of TA. Thus, UBM findings of these patients were compared with those from 18 patients with negative biopsy. On UBM we searched for the presence of a hypoechoic effect surrounding the walls of the temporal arteries, the so-called halo sign, as well as an intra-arterial middle reflexive filling, the so-called intra-arterial filling.The halo sign and/or the intra-arterial filling were found in 8 (100%) of 8 patients with biopsy-proven TA. However, 10 (55.5%) of 18 patients with a negative biopsy presented one or both of these two UBM findings. On the other hand, the absence of these two parameters on the UBM of a patient with TA strongly suggests that the temporal artery biopsy will be negative (negative predictive value=100%).This preliminary work suggests that UBM may play a role in predicting a negative result of the temporal artery biopsy in patients with TA. In the present series approximately 30% of the patients could be spared this surgical procedure and its possible complications.

Our aim was to evaluate the potential effect of imatinib mesylate (IM), a small molecule that specifically inhibits the tyrosine quinase receptors, on the proliferation and invasive abilities of two human retinoblastoma (Rb) cell lines. Furthermore, the ability of IM to radiosensitize Rb cells was evaluated. The potential targets of IM (C-kit, PDGRF-α and -β, and c-Abl) were also investigated in these cell lines.Two human Rb cell lines (WERI-RB-1 and Y79) were cultured under normal growth conditions. An MTT-based proliferation assay and a Matrigel invasion assay were performed with and without exposure to 10 μM of IM. The cells were also irradiated with graded dosages of 0, 2, 4, 6, 8, and 10 Gy with and without IM and their proliferations rates were analyzed. Western blot and immunocytochemical analysis of cytospins were performed to evaluate the expression of C-kit, PDGRF-α and -β, and c-Abl.When IM was added to both cell lines a statistically significant (P0.05) reduction in proliferation and invasive ability were observed. Exposure to IM also significantly increased the radiosensitivity of both Rb cell lines. The c-Abl expression was strongly positive, PDGRF-α and -β expression were also positive but the C-kit expression was negative in both cell lines.These results indicate that Gleevec may be useful as an adjuvant treatment in Rb patients, specially those considered for radiation therapy.

Objective To compare the costs of the new fixed combinations for glaucoma medical therapy. Methods The studied drugs were: Cosopt (5-mL bottle), Combigan (5-mL bottle) and Xalacom (2.5-mL bottle). Five bottles of each drug were obtained from pharmacies, and the medications lot numbers were recorded. To calculate the drop volume, 10 drops and 1 mL of each bottle were weighed with a digital precision scale. Drop volume was calculated by the relation between volume and weight. The cost of each bottle of medication was determined from the average retail price in Canada. The prices were obtained in Canadian dollars (dollars). Results The drops of Cosopt (39.60 +/- 0.45 microL) were considerably larger than the drops of Combigan (33.75 +/- 0.60 microL) and Xalacom (30.87 +/- 0.37 microL). The average number of drops per millilitre varied from 25.25 +/- 0.29 (Cosopt) to 32.40 +/- 0.39 microL (Xalacom). Combigan presented the lowest daily cost (dollars 0.87 +/- 0.02) followed by Xalacom (dollars 1.09 +/- 0.01) and Cosopt (dollars 1.22 +/- 0.01). The average cost by year varied from dollars 316.75 +/- 5.59 (Combigan) to dollars 445.96 +/- 5.16 (Cosopt), with a total difference of dollars 129.21 per year of treatment. Conclusions There was a statistically significant difference in average drop size and cost among the three studied drugs. Combigan presented the lowest daily cost followed by Xalacom and Cosopt.

The liver is a major site of metastasis for human malignancies, yet the factors that regulate tumor cell survival and growth in this organ remain elusive. Previously, we reported that M-27(IGF-IR) murine lung carcinoma cells with ectopic insulin-like growth factor-1 (IGF-I) receptor overexpression acquired a site-specific, liver-metastasizing potential. Gene expression profiling and subsequent RNA and protein analyses revealed that this was associated with major changes to the expression of extracellular matrix (ECM) protein-encoding genes including type III, IV and XVIII collagen genes, and these changes were also observed in the respective tumors in vivo. Because type IV collagen was the most prominently altered ECM protein in this model, we further analyzed its functional relevance to liver metastasis. M-27 cells stably overexpressing type IV collagen α1 and α2 chains were generated and their growth and metastatic properties investigated. We found that these cells acquired a site-selective growth advantage in the liver and this was associated with cell rescue from anoikis in a collagen IV/α2 integrin/FAK-dependent manner and increased responsiveness to IGF-I. Conversely, collagen IV or focal adhesion kinase (FAK) silencing by small-interfering RNA in highly metastatic tumor cells enhanced anoikis and decreased liver metastases formation. Moreover, analysis of human surgical specimens revealed uniformly high collagen IV expression in 65/65 hepatic metastases analyzed, regardless of tissue of origin, whereas it was variable and generally low in 50/50 primary colorectal carcinoma specimens examined. The results suggest that collagen IV-conveyed signals are essential cues for liver metastasis in diverse tumor types and identify mediators of collagen IV signaling as potential therapeutic targets in the management of hepatic metastases.

Purpose The experience with 125Iodine (I125) plaque brachytherapy in the treatment of IM at the Princess Margaret Hospital/University Health Network is the subject of the report to follow. Methods All cases of IM submitted to I125 plaque radiotherapy were included. Patients' demographic, clinical, management, and follow-up data were reviewed. Outcome measures included rates of tumor control, eye preservation, systemic metastases, and brachytherapy-related complications. Results Fourteen IMs were included in the study. All patients had blue/green irises. Mean largest basal dimension and thickness were 7.1 +/- 2.1 mm (range, 4.0 to 11.5 mm) and 2.2 +/- 0.8 mm (range, 1.0 to 3.5 mm), respectively. Ten patients (71%) had seeding and 2 (14%) had glaucoma at presentation. Median follow-up was 26.6 +/- 19.5 months (range, 6 to 72 months). Tumor control was achieved in 100% of the cases and no eye was enucleated because of radiation-induced complications. At last visit, all patients were alive and free of metastasis. Final visual acuity was the same as or better than before treatment in 9 patients (75%). Cataract was the most common complication (8; 75%), followed by persistent glaucoma (2; 17%) and anterior uveitis (1; 8%). No other significant complication was seen during the follow-up period. Conclusion Plaque radiotherapy is a safe and effective conservative treatment option for IM, although cataract is a common, yet treatable, complication. This treatment scheme circumvents an intraocular procedure and may avoid the dissemination of malignant cells, and provides a margin of safety in the treatment of clinically undetectable disease.

We describe the unusual diagnosis of a ciliary body medulloepithelioma by histopathology of a subretinal membrane obtained from vitreoretinal surgery of a 10-year-old boy. The patient had a history of perforating trauma OS 2 years earlier, and both fundus exam and B-scan ultrasound revealed only a retinal detachment with a subretinal membrane. No detectable mass was present.The membrane removed from underneath the peripheral retina revealed a blue cell tumor confirmed by histopathology and immunohistochemistry to be a primitive neuroectodermal tumor. Currently, the patient has been followed for 5 years with no signs of recurrence.

espanolCaso clinico: Se describe el caso histopatologico poco comun de un meduloepitelioma del cuerpo ciliar, encontrado en una membrana sub-retiniana, que se obtuvo durante la cirugia vitreo-retiniana de un nino de 10 anos de edad. Dicho paciente tenia un historial de haber tenido un trauma perforante en el ojo izquierdo dos anos antes. Tanto el examen oftalmoscopico como el ultrasonido revelaban solo un desprendimiento de retina con una membrana sub-retiniana. No habia evidencia de una masa intraocular. Discusion: La histopatologia y los estudios de inmunoquimica de la membrana extraida de la retina periferica, revelaron un tumor de celulas azules, compatibles con un tumor primitivo de origen neuroectodermico. Al momento, el paciente ha tenido cinco anos de seguimiento sin recurrencia alguna. EnglishCase report: We describe the unusual diagnosis of a ciliary body medulloepithelioma by histopathology of a subretinal membrane obtained from vitreoretinal surgery of a 10-year-old boy. The patient had a history of perforating trauma OS 2 years earlier, and both fundus exam and B-scan ultrasound revealed only a retinal detachment with a subretinal membrane. No detectable mass was present. Discussion: The membrane removed from underneath the peripheral retina revealed a blue cell tumor confirmed by histopathology and immunohistochemistry to be a primitive neuroectodermal tumor. Currently, the patient has been followed for 5 years with no signs of recurrence.

Purpose: To examine the immunohistochemical profile of Hsp90 in uveal melanoma and the effects of Hsp90 inhibitor 17-AAG, in uveal melanoma cell lines. Methods: Hsp90 expression was studied in 44 sections of human uveal melanoma and in five uveal melanoma cell lines (92.1, OCM-1, MKTBR, SP6.5 and UW-1). Sulfurhodamine-B based proliferation assay was assessed with a range of concentrations of 17-AAG. Changes in cell migration and invasion were evaluated in vitro in the presence or absence of 17-AAG. Cell cycle fractions were determined by flow cytometry and the caspase 3 protease activity was detected using the BD ApoAlertTM Caspase Colorimetric Assay. Expression of intracellular proteins was determined by Western blot analysis. Results: Immunohistochemical expression of Hsp90 was identified in 68 % of the paraffin embedded sections and was significantly associated with largest tumor dimension. A statistically significant reduction on proliferation rate of uveal melanoma cell lines was observed with drug concentrations of 100 μM to 1 μM and also a reduction of their migratory and invasive capabilities. Exposure to 17-AAG induced accumulations of cells in G1 and loss of cells in S phase and also a significant increase in Caspase 3 protease activity. The cytotoxic effect of 17-AAG was associated with decreased levels of phospho-AKT after 24 h exposure to the drug. Conclusions: The immunohistochemical expression of Hsp90 in uveal melanoma indicates worse prognosis. Inhibition of HSP90 function by 17-AAG had an effect on cell motility and invasive potential, inducing cell cycle arrest and promoting apoptosis. Further trials in uveal melanoma models should be undertaken to study the effect of 17 AAG to target Hsp90 in vivo.

Purpose: We previouly demonstrated the feasibility of a human uveal melanoma GFP model in nude mice. We were able to monitor the preferential colonization of the liver by malignant cells during a 20-day period. In this study we extended the observation period in order to observe disease progression and metastatic growth. Methods: Five hundred thousand, GFP transfected, human primary uveal melanoma cells (92.1) were injected into the tail vein of 30 nude mice at time zero. Starting at day one, five mouse per week was imaged, using an abdominal incision to expose the liver, for up to 60 minutes before sacrifice. The liver was imaged in vivo and post mortem, while the lungs, spleen, and kidney were all examined post-mortem for GFP expression. Histopathological examination of all organs was performed to ensure that the GFP signal was arising from malignant cells. Results: In vivo imaging of the liver revealed positive GFP signal in all mice throughout the experiment. Malignant cells seeded the liver after injection, but there was no apparent tumor growth upon completion of the experiment. The micrometastatic foci remained viable without changes in size or intensity of the signal. No tumors were seen in any other organ at the end of the experiment. Histopathology confirmed that the cells emitting GFP were malignant cells. Conclusions: The results of this uveal melanoma model show great promise for understanding the previously unobservable interactions between single human uveal melanoma cells and native liver tissue. The fact that our cells successfully colonize the liver yet remain dormant for six weeks should actually mirror the disease in humans; metastases in patients takes roughly five to ten years to develop.

Purpose: Uveal melanoma (UM) cells lines, when exposed to blue light in vitro, show a significant increase in proliferation. In order to see if the same effect would be seen in vivo, we investigated the influence of blue-light exposure in an animal model of UM. Methods: Twenty albino rabbits were injected with 1 million human UM cells (92.1) into the suprachoroidal space of the eye. Animals were immunosuppressed using cyclosporin A throughout the 8 week long experiment. The animals were divided into two groups of 10 animals each. The experimental group was exposed to blue-light, while the control group was protected from blue-light using a yellow-filter. Intraocular tumor growth was evaluated weekly by fundoscopic examination. One animal was sacrificed per week, after the 2nd week, in order to evaluate progression of the disease. The eyes were removed after sacrifice and the proliferation rates of the re-cultured cells obtained from the intraocular tumors were performed using the Sulfordhamine-B assay. The Student's t–test was used to compare results for statistical significance. Results: Re-cultures of UM cells were establish from 4 and 5 rabbits of the experimental and control group respectively. Cells were re-cultured for a very short period of time (1 passage only) in order to maintain any in vivo cellular changes. The exposure of rabbits to blue light led to an increase in proliferation of the cell lines derived from intraocular tumors compared to the control (p=0.001). Conclusions: There is increasing amount of data suggesting that Blue-light, one of the components of visible light, may influence the progression of UM. Our results warrant further studies to relate the importance of Blue-Light filtering lenses for UM patients.

Purpose A chalazion, localized lipogranulomatous inflammation of the eyelid, may simulate various eyelid lesions. This study was conducted to determine the accuracy of the clinical diagnosis of chalazion and demonstrate the importance of histopathological confirmation of the diagnosis. Methods Histopathological diagnoses of 1060 cases with the clinical diagnosis of chalazion, submitted to the Henry C Witelson Ophthalmic Pathology Laboratory and Registry between September 1993 and December 2001, were retrospectively evaluated. Discrepancies between clinical and histopathological diagnoses were classified. Results A total of 1033 (97.4%) of the 1060 cases were clinically diagnosed as primary and the remaining 27 (2.6%) as recurrent chalazions. Agreement was noted between clinical and histopathological diagnoses in 992 (93.6%) cases. Of the 68 (6.4%) clinically misdiagnosed cases, 15 (1.4%) were found to be malignant, two (0.2%) premalignant, and 51 (4.8%) benign conditions. Sebaceous cell carcinoma was the most commonly missed malignancy (12 cases, 1.1%) followed by basal cell carcinoma (three cases, 0.3%). Premalignant lesions, which masqueraded as chalazion, were chronic inflammation with cellular atypia and mitotic figures (two cases, 0.2%). Of these 17 cases with premalignant and malignant histopathologies, only six (35.3%) had a clinical diagnosis of recurrent chalazion, whereas the others (64.7%) were primary cases. Of the various benign conditions that were misdiagnosed as chalazion, different types of chronic inflammation (24 cases, 2.2%) were the most frequent. Conclusions A number of different benign, premalignant, and malignant conditions may clinically masquerade as a chalazion. Delayed diagnosis and treatment of sebaceous cell carcinoma, which is the most frequently missed malignancy, may be life threatening for the patient. Therefore, all chalazion specimens, primary or recurrent, should be submitted for histopathological examination.

A 68-year-old Caucasian male was referred for evaluation and follow-up of unilateral glaucoma resistant to control with topical medication. Corrected visual acuity was 20/20 in the right and 20/25 in the left eye. Biomicroscopy was normal and the intraocular pressure (IOP) was 14 mm Hg in the right eye. In the left eye, ciliary injection, a diffuse iris hyperchromia (figure 1A), discrete corneal oedema with the presence of sparse pigment deposits on the endothelium (figure 1B), and mild anterior chamber reaction (+/4+) were observed. The angle was obstructed inferiorly by the pigment deposition, while the parts of the angle that were visible showed increased pigmentation of the trabecular meshwork during gonioscopy. The iris surface was smooth and the crypts were absent. The pupil was round but fixed in medium mydriasis with a posterior synechia seen at 1 h. In addition, the lens had nuclear sclerosis and the IOP was measured at 58 mm Hg. Funduscopy disclosed increased cup-to-disc ratio in the left (0.7) compared with the right eye (0.4), but was otherwise unremarkable. Figure 1 Patient presents with left hyperchromic heterochromia (A). Observed in (B) is a smooth surface and an absence of crypts. Pigment deposits could be seen over the lens capsule and the endothelium side of the cornea. Diffuse hyperreflectivity of the iris in the left is shown in (C). Normal UBM in the right eye is also shown for comparison (D). Normal reflectivity of the ciliary processes in the left eye can be seen in an UBM (E). The patient's relevant medical history included controlled hypertension and a basal cell carcinoma in the left arm resected 2 years before. There was no evidence of congenital ocular or oculodermal melanocytosis in the patient or his family. Presently, differential diagnoses include diffuse iris melanoma and diffuse iris melanocytoma. Ultrasound biomicroscopy was performed showing a …

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the central nervous system found in immunodeficient patients, most frequently now in those infected with HIV. It may represent the initial manifestation of HIV infection. Since the central visual pathways may be affected, a variety of neuro-ophthalmic signs and symptoms can manifest. We studied the clinical, radiographic and histopathological characteristics of patients with PML.The charts of 13 patients in whom PML was diagnosed in the Neuro-AIDS clinic at the Montreal Neurological Institute between November 1987 and March 1995 were reviewed. The diagnosis of PML was established by characteristic clinical features together with typical computed tomographic or magnetic resonance imaging findings, such as nonenhancing low-density (on computed tomography) or hyperintense (on T2-weighted magnetic resonance imaging) white-matter lesions, without mass effect. Neuro-ophthalmic findings were based on clinical examination by an ophthalmologist, neuro-ophthalmologist or neurologist. Tissue for pathological examination was obtained by biopsy in one case and at postmortem study in a second case.The most common finding was homonymous hemianopia, in five patients (38%). Other features included nystagmus (in two patients), diplopia with cranial nerve palsy (in one) and cortical blindness (in one). One of the patients exhibited involvement of the brain stem, a site not usually affected by this demyelinating process.The diagnosis of PML should be considered in immunocompromised patients with neuro-ophthalmic findings, particularly those with homonymous hemianopia.

To investigate the expressivity of S-100 beta antibodies in choroidal melanomas and to compare it with that of S-100 protein and HMB-45.Twenty-seven choroidal melanoma specimens obtained from the McGill University Ophthalmic Pathology Registry were classified as spindle cell, epithelioid cell or mixed-cell type. Immunohistochemistry was performed using the standard peroxidase-antiperoxidase technique with monoclonal HMB-45, polyclonal S-100, polyclonal S-100 beta and monoclonal S-100 alpha beta antibodies in formalin-fixed, paraffin-embedded sections.Intensity of immunoreaction. The result was considered positive when at least five focal areas of stained cells were observed within the tumour.All 27 tumours were positive for HMB-45, 19 (70%) for S-100, 23 (85%) for S-100 beta, and 21 (78%) for S-100 alpha beta. No correlation was found between the intensity of the immunoreaction and cell classification.HMB-45 is the most reliable marker for choroidal melanomas. S-100 beta is a more sensitive marker than S-100 for choroidal melanomas regardless of cell type. Contrary to previous reports, S-100 beta should not be considered a useful immunomarker to differentiate between primary choroidal melanoma and cutaneous melanoma metastatic to the choroid.

This study was performed to determine the prognostic significance of the presence of loops defined as periodic acid-Schiff-positive fibrovascular septa that completely surround lobules of tumor cells in cases of uveal melanoma.The presence of loops was evaluated using an ordinary light microscope and routinely stained periodic acid-Schiff and hematoxylin sections from 496 posterior uveal melanomas without knowledge of the follow-up data on the patient.At 15 years, survival decreased from 67.5% to 33.8% when complete loops were present. Univariate Cox regression analysis indicated that the presence of loops was an indicator of poor outcome, and was better than age but not as good as the mean diameter of the largest nucleoli, cell type, or tumor size.The presence of loops, as evaluated in this study, was not as strong an indicator of poor outcome as were loops assessed in a previous study of 234 cases from another laboratory. The authors suspect this difference may be due to their only using routinely stained sections without a green filter, as was used in previously reported studies. The authors description of loops does not require any special equipment and gives sufficiently useful results to justify its inclusion by the pathologist in reports of such specimens. A description of vascular loops should be added to the use of the modified Callender cell type, tumor dimensions, mitotic count, extraocular extension, and lymphocytic infiltration in the final pathologic report.

Basal cell carcinoma is the most common eyelid malignancy, accounting for approximately 90% of malignant eyelid tumours. Despite its prevalence in adults, it is extremely rare in children, and usually occurs in the setting of a known genetic defect or following radiotherapy treatment. We report three cases of de novo basal cell carcinoma in children. These children had no known genetic syndromes and had not undergone radiotherapy.

To investigate using immunohistochemistry the unusual finding that tumor infiltrating lymphocytes (TIL) in uveal melanomas are associated with a higher mortality rate.We performed immunohistochemistry for B and T lymphocytes on 80 uveal malignant melanomas, which previously had been reported to contain more than 100 TIL per 20 high-powered fields. In a second study of 90 patients, we counted the number of immunohistochemically stained T lymphocytes per 20 high-powered fields in uveal melanomas from 30 patients who survived at least 15 years after enucleation, from 30 patients who died with metastasis within 2 years, and from 30 patients who died with metastasis more than 10 years after enucleation.T cells predominated in 73.8% of the 80 patients, and B cells were more prevalent in 13.8%. T cells were usually scattered, and B cells were usually in clumps. Post-enucleation 18-yr mortality from metastasis was 73% for patients with either T- or B-cell predominance of their TIL. The mortality rate was 32% for patients with few TIL. The patients who survived at least 15 yrs after enucleation had fewer T lymphocytes infiltrating their uveal melanomas than the two groups of patients who died with metastasis.The pattern of the TIL was different for T and B cells in uveal melanomas. T-lymphocytic infiltration is associated with death due to metastasis.

The authors compared the immunohistochemical reactivity of 13 uveal nevi and 20 uveal melanomas for HMB-45, S-100 protein, and neuron-specific enolase (NSE) in formalin-fixed, paraffin-embedded sections. All 33 of the lesions were positive for HMB-45. The false-negative rates for S-100 protein and NSE were 21% and 18%, respectively. If only strongly positive reactions were considered, more than 50% of the tumors would be interpreted as negative for S-100 protein and NSE. Nevi stained with less intensity than melanomas using all three antibodies. The expression of HMB-45 appeared to be greater in active nevi than in inactive nevi. There was a weak association between S-100 protein reactivity and the ability of the uveal melanomas to metastasize (P = 0.1); however, the standard deviation of nucleolar area was a much better predictor (P = 0.02). These results indicate that pathologists will find HMB-45 to be a useful tool in differentiating uveal melanoma from nonmelanocytic tumors.

In 150 retinoblastomas the authors found a uniform thickness of the cuff of viable retinoblastoma cells that surrounds blood vessels. The mean thickness was 98.7 microns with a standard deviation of 11.9 microns. The cross-sectional area of the cuff was negatively correlated with the mitotic activity in the cuff and positively correlated with the diameter of the central vessel. The mitotic activity in the cuff of cells was inversely related to the distance from the central blood vessel. When the cuff was divided into three concentric rings, the inner ring contained a mean of 6.2 mitotic figures, the middle ring contained a mean of 2.9 mitotic figures, and the outer ring contained a mean of 0.6 mitotic figures. This pattern of growth is similar to that observed in other rapidly growing neoplasms in humans and experimental animals. In these tumors this pattern results from reduction in oxygen tension with increased distance from the central blood vessel.

Seventy bone marrow biopsies belonging to 53 patients with non-Hodgkin lymphomas, chronic lymphocytic leukemia, and micosis fungoides were studied. Bone marrow involvement was analyzed in correlation to staging before and after treatment. Bone marrow involvement was most frequently seen in CLL and IL followed by WDLL and PDLL/N and PDLL/D. Highest incidences after treatment were in CLL, WDLL, and PDLL/N and PDLL/D. With respect to staging, WDLL disseminated to bone marrow only in the late stages (III or IV), whereas the nodular and diffuse forms of PDLL presented similar infiltration in all stages. HLL and IL presented a slight trend to infiltrate only in the later stages. The pattern of bone marrow infiltration was also analyzed considering staging before and after treatment. No clear correlation was observed between staging and a specific pattern of bone marrow involvement in most cases, and disease evolution and treatment do not seem to change infiltration pattern.