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J Pe'er

Publications and source records attributed to J Pe'er.

At least 19 recordsLinked to original sources
PubMed1998

Imaging the microvasculature of choroidal melanomas with confocal indocyanine green scanning laser ophthalmoscopy.

OBJECTIVE: To image the microvasculature of choroidal melanoma with a new confocal scanning laser ophthalmoscope. METHODS: Eighteen consecutive patients, each with a unilateral choroidal melanoma, were examined prospectively. Indocyanine green angiography was performed with a new confocal scanning laser ophthalmoscope that enabled serial optical sectioning through the tumor. Two additional patients were studied with indocyanine green angiography and confocal scanning laser ophthalmoscopy just before enucleation for posterior choroidal melanomas. The histologic identification of microvasculature patterns was compared with the angiograms for these patients. RESULTS: In the series of 18 patients, 16 (89%) indocyanine green angiograms with optical sectioning revealed tubular structures within the melanoma that were identified as tumor vessels based on their angiographic appearance. The microvasculature patterns identified by indocyanine green angiography correlated well with the histologic appearance of these microvasculature patterns in both patients for whom histologic verification was available. CONCLUSIONS: This preliminary study suggests that indocyanine green angiography with confocal scanning laser ophthalmoscopy images the microvasculature of choroidal melanomas and may be capable of detecting microvasculature patterns that have been shown to be prognostically significant from histopathological studies.

Adult↗
PubMed1998

Biologic determinants of uveal melanoma metastatic phenotype: role of intermediate filaments as predictive markers.

The long-range goal of our research is to develop intervention strategies based on newly discovered biologic mechanisms responsible for the invasive dissemination of metastatic uveal melanoma. To accomplish this goal, we have focused on the biologic relevance of novel marker proteins contributing to the uveal melanoma metastatic phenotype. The expression of vimentin intermediate filaments (IFs), a mesenchymal marker, is typical of melanomas, whereas carcinomas typically express keratin IFs, which are markers for epithelia. Thus, cells that coexpress both IFs are regarded as "interconverted" in that they display both mesenchymal and epithelial phenotypes. Although the biologic functions of IFs have remained enigmatic, there is substantial support to suggest that the significance of vimentin/keratin coexpression is linked with poor patient outcome in cutaneous melanoma. Our data demonstrate that human uveal melanoma cell lines (isolated from primary choroidal or ciliary body melanomas and from foci of metastatic uveal melanoma to the liver), which contain predominant populations of cells that coexpress vimentin/keratins 8 and 18 (keratins 8,18) IFs, were 6-fold more invasive through collagenous extracellular matrices in vitro, compared with uveal melanoma cells expressing vimentin only, and were 8- to 13-fold more invasive than normal uveal melanocytes. Colocalization of vimentin/keratins 8,18 in cell cultures was corroborated by immunohistochemistry in histologic sections of tumors from which the cell lines were derived. Minor populations of these cells also coexpressed keratins 13 and 17. Experimental down-regulation of the predominant keratins 8,18 in the interconverted cells, using 16-mer antisense oligonucleotides, resulted in a significant decrease in the migratory ability of the cells-similar to levels achieved by cells positive only for vimentin. These findings provide justification for additional studies of the association between coexpression of IFs vimentin/keratins 8,18 and uveal melanoma metastasis.

Antisense Elements (Genetics)↗
PubMed1997

An experimental model for infiltration of malignant lymphoma to the eye and brain.

Currently there is no adequate experimental model available whereby the lethal infiltration of malignant lymphoma to the eye and CNS can be studied. Variant S49 mouse lymphoma cells that exhibit cell-cell adhesion properties (named Rev-2-T-6) were inoculated intraperitoneally into Balb/C mice at the ages of 6-60 days postnatal. Mice inoculated between days 6-11 postnatal developed signs of eye and CNS involvement with an apparent peak (58% of mice) at day 7. None of the mice inoculated beyond day 11 exhibited such signs. Histological analysis of these sites revealed tumorous infiltrates into a variety of structures in the orbit, intraocular tissues, along the optic nerve and in the brain. Additional analysis of the histopathological data, based on the structures demonstrating the highest frequency of lymphoma infiltration, suggests preferred routes of lymphoma entry to the brain and eye. Thus, entry to the brain can occur mainly through the choroid plexus and cranial nerves or cranial nerve ganglia. Entry to the eye may occur from the brain (along the optic nerve), and through hematogenous infiltration of orbital structures. No data were found that would support retrograde infiltration of the lymphoma from the eye to the brain. These findings present an experimental model for addressing the molecular mechanisms that govern homing of malignant lymphoma to the eye and brain, as well as the development of experimental therapeutic modalities for malignant lymphoma in these organs.

Animals↗
PubMed1997

Multiple conjunctival metastases as the initial sign of metastatic uveal melanoma.

PURPOSE: To describe a 31-year-old patient who was initially examined with a uveal malignant melanoma metastatic to the ipsilateral conjunctiva. METHOD: Thirteen months after ruthenium 106 plaque therapy for a ciliochoroidal malignant melanoma, numerous pigmented conjunctival lesions first appeared. RESULTS: These lesions were excised and found to be metastases of melanoma to the superficial subepithelial conjunctival tissue, composed of epithelioid cells. CONCLUSION: The appearance of darkly pigmented conjunctival lesions in a patient known to harbor a uveal malignant melanoma, even though lacking any evidence of extrascleral extension or metastatic involvement, may indicate metastatic disease.

Adult↗
PubMed1997

Mitomycin C treatment for conjunctival-corneal intraepithelial neoplasia: a multicenter experience.

OBJECTIVE: The purpose of the study is to evaluate the efficacy and risks of topical mitomycin C (MMC) for conjunctival-corneal intraepithelial neoplasia (CCIN). DESIGN: The study design was a clinical case series of CCIN. PARTICIPANTS: Seventeen patients, 16 with biopsy-confirmed CCIN and 1 with invasive squamous cell carcinoma (SCC), were included in the study. INTERVENTION: Patients received topical drops of MMC 0.02% to 0.04% four times daily from 7 to 28 days. Retreatment was done in cases of lesion recurrence. MAIN OUTCOME MEASURES: The size of the CCIN before and after the treatment and ocular complications post-MMC application were evaluated. RESULTS: Ten patients remained disease-free after one course of MMC application. In one case, residual CCIN remained very small without regrowth. In the one patient with invasive SCC and in five patients with CCIN, regrowth occurred within 6 months of the first treatment. After retreatment, invasive SCC and CCIN in an additional two patients were eradicated. In two cases, although the size of the lesions decreased after two and three applications of MMC, regrowth occurred, and the CCIN returned to its original size. In the final case, limited recurrence has occurred and no retreatment has been done. The complications of MMC use included mild-to-moderate conjunctival hyperemia and mild allergy, which resolved after discontinuation of the treatment. Severe pain manifested when treatment was longer than 14 days. CONCLUSIONS: Application of topical MMC is an efficient treatment for most but not all cases of CCIN.

Administration, Topical↗
PubMed1997

Rubeosis iridis in retinoblastoma. Histologic findings and the possible role of vascular endothelial growth factor in its induction.

PURPOSE: Iris neovascularization (rubeosis iridis) is a common finding in eyes harboring retinoblastoma. The purpose of the current study is to evaluate the histologic factors that may affect the development of rubeosis iridis in eyes with retinoblastoma and to examine whether vascular endothelial growth factor (VEGF), a hypoxia-induced angiogenic factor, is produced by hypoxic retinoblastoma and retinal cells in these eyes. MATERIALS AND METHODS: One hundred eighty-one enucleated eyes containing retinoblastoma were the source for the current study. Histologic slides were evaluated for the presence and degree of rubeosis iridis as well as for other histologic factors. Univariate and multivariate statistical analyses were performed to find a correlation between rubeosis iridis and the other histologic factors. Eight of the eyes underwent in situ hybridization with a specific VEGF mRNA probe to locate tumor and retinal cells that may produce this hypoxia-induced angiogenic factor. RESULTS: The amount of tumor necrosis as well as choroidal and optic nerve invasion was found to be one of the most important factors that correlated with the presence and degree of rubeosis iridis in the examined eyes. All eight eyes that underwent in situ hybridization analysis showed strong signals of VEGF mRNA in retinoblastoma cells around necrotic regions and in the outer nuclear layers in areas of detached retina. CONCLUSIONS: There exists an association between rubeosis iridis and histologic factors found in advanced stages of retinoblastoma, especially the amount of tumor necrosis. Vascular endothelial growth factor may well be an angiogenic factor that is secreted by the hypoxic retinoblastoma and retinal cells and, reaching the iris, causes (presumably in collaboration with other factors) rubeosis iridis.

Child↗
PubMed1997

The microcirculation of choroidal and ciliary body melanomas.

The microcirculation of ciliary body and choroidal melanomas is remodelled into patterns. The presence of microvascular networks, composed of back-to-back loops that encircle microdomains of tumour, and parallel vessels with cross-linking, are associated with death from metastatic melanoma. The formation of these complex vascular patterns may result from reciprocal interactions between the tumour cell and the extracellular matrix, and pattern formation may reflect an invasive tumour cell phenotype. Ciliary body and choroidal melanomas are among the few forms of cancer treated before a pathologist assigns a grade to indicate whether tumour is likely to follow a benign or aggressive course. There is evidence to suggest that prognostically significant microcirculatory patterns may be detectable by non-invasive imaging techniques that may provide a substitute for biopsy to guide the clinical management of patients with these sight- and life-threatening tumours.

Choroid Neoplasms↗
PubMed1997

Thirty years of penetrating keratoplasty in Israel.

We studied the indications for keratoplasty and their changes during 30 years in Israel by retrospective evaluation of pathologic records of 1,018 corneal buttons (from 1961 to 1990). The population included 634 (62.3%) male patients and 384 (37.7%) female patients. Keratoconus (n = 222, 21.8%) was the most common indication, followed by corneal graft failure (n = 113, 11.1%), herpetic infections (n = 95, 9.3%), ocular trauma (n = 87, 8.5%), scarring (n = 74, 7.3%), pseudophakic bullous keratopathy (n = 72, 7.1%), nonherpetic infections (n = 71, 7.0%), and other indications. Whereas ocular infections were the most common indications for keratoplasty before 1970, keratoconus has been the most common indication since 1970. Pseudophakic bullous keratopathy became the second most common indication (13.8%) between the years 1981 and 1990. The number of keratoplasties increased in Israel during the past three decades, and the low percentage of pseudophakic bullous keratopathy is related to the types of intraocular lenses that we implanted in the late 1970s and the early 1980s.

Corneal Diseases↗
PubMed1996

Use of mitomycin C in the treatment of conjunctival primary acquired melanosis with atypia.

A patient who had primary acquired melanosis with marked atypia shown on histological studies received topical 0.02% mitomycin C for 2 weeks and 0.04% mitomycin C for an additional 2 weeks. Conjunctival biopsy specimens were obtained to evaluate the efficacy of the treatment. After the first course of mitomycin C administration, some decrease of conjunctival pigmentation was seen, and histological studies disclosed a lower degree of atypia. After the second application of mitomycin C, the pigmentation disappeared except for one small spot that contained only a few typical melanocytes on histological study. The clinical findings did not change during 7 months of follow-up. No adverse reactions to topical mitomycin C occurred except for mild conjunctival hyperemia at the end of the courses of treatment. Administration of topical mitomycin C may be an effective medical treatment for primary acquired melanosis with atypia.

Administration, Topical↗
PubMed1996

Streaming conjunctiva.

BACKGROUND: Epithelial proliferation is linked with cell displacement. When a cell divides, one of its progeny replaces the dividing ancestor and the other is displaced into a more remote location that has to be vacated first by peripheral cells. As cells are neither pushed nor pulled in a mechanical sense, and since they do not move by their own means, this displacement is best regarded as streaming. The purpose of the present study was to measure epithelial cell streaming in adult rat conjunctiva. METHODS: Twenty-seven female adult rats were injected i.p. with 18.5 KBq [3H]-thymidine/g body weight, specific activity 185 GBq/mMol. Three rats were killed at different times up to 28 d. Eyes and eyelids were removed in one piece, cut along the pupillary-optic nerve line into 5-microns-thick sections, and prepared for autoradiography. In each eye, the entire upper conjunctiva extending from limbus to the palpebral muco-cutaneous junction was scanned with an ocular micrometer grid. The limbus served as point of origin. The x, y coordinate of each nucleus with two grains or more and its grain content were recorded. RESULTS: One hour after labeling, labeled cells were spread evenly along the basal layer. Cells of the upper layers were not labeled. As time passed by, labeled cells in the fornix became more abundant, while in the limbus and palpebral margin, their frequency declined. Labeled cells streamed from the limbus and palpebral muco-cutaneous junction to the fornix. Bulbar conjunctival epithelia streamed at a velocity of 13.2 microns/day. Epithelia in the palpebral conjunctiva streamed at a velocity of 11.8 microns/day. At the same time cells streamed from the basal layer to the epithelial surface at a velocity of 0.4 microns/day. Generation time was 3.9 days. CONCLUSIONS: Bulbar and palpebral conjunctivae are two independent cell kinetic systems that originate in two stem cell regions, one in the limbus and the other in the muco-cutaneous junction. Each system is made of two compartments, a progenitor where cells proliferate, and a compartment of non proliferating end cells. Progenitors created in the first, enter the second and turn into end cells. Ultimately they die in the fornix. The undetermined limbus stem cell generates two epithelial cell lines, a corneal and a conjunctival.

Animals↗
PubMed1996

Glandular tumors of the lacrimal sac. Their histopathologic patterns and possible origins.

PURPOSE: To describe and characterize the primary lacrimal sac epithelial tumors of glandular origin, and to describe their possible source from glands in the lacrimal sac and nasolacrimal duct walls. METHODS: The authors conducted a clinicopathologic study on 14 patients with epithelial lacrimal sac tumors of possible glandular origin. In addition, they reviewed 35 surgical specimens of the lacrimal sac and nasolacrimal duct region and 13 cadaver specimens of the lacrimal sac region. RESULTS: Six of the tumors were benign: four were oncocytomas and two were pleomorphic adenomas. Eight of the tumors were malignant: three were oncocytic adenocarcinomas, three were adenoid cystic carcinomas, and two were adenocarcinomas. All tumors were from adults, ranging in age from 38 to 87 years. Twenty-eight of the 47 specimens of lacrimal sac and nasolacrimal duct region showed mixed glands of serous and mucous elements. CONCLUSIONS: Although rare, benign and malignant glandular lacrimal sac tumors should be considered in the differential diagnosis of lacrimal sac obstruction. Their possible origin is from the normal glands that exist under the lacrimal sac and nasolacrimal duct epithelium.

Adenocarcinoma↗
PubMed1996

Epithelial cell migration in the normal rat lens.

The purpose of the present study was to estimate the rate of the rat lens epithelium displacement. Twenty-four adult male rats were injected intraperitoneally with 18.5 kBq/g [3H] thymidine. Rats in groups of three were killed at the following times: after one hour, 3, 6, 9, 12, 15, 18 and 21 days. The enucleated eyes were fixed in formalin, embedded in paraffin, cut into 5 microns-thick sections, and subjected to autoradiography. The number of cells was counted, and the x-coordinate of each nucleus with three grains or more, and its grain content were recorded. Statistical analysis included analysis of variance and linear regression. The average lens diameter was 68 fields of 75 microns each (5.1 mm). Cell displacement was measured in two regions: Region A, the equatorial region, extending from field 0-20, and region B extending from field 20 to the lens center (field 34). Cells in region A are divided into two kinetic compartments, progenitor (P-cells) occupying fields 9-20, and non-proliferating (Q) cells occupying fields 0-8. Cells advanced from the P into the Q-compartment at a velocity of 21.8 microns/day. Cells did not move between field 20 and the lens center. These findings resemble kinetically renewing tissues, e.g. epidermis and crypt-villus in the gastrointestinal mucosa.

Animals↗
PubMed1996

Vinblastine toxicity to the ocular surface.

Local ocular exposure to antineoplastic drugs occurs either during regular use of some of these drugs in ophthalmology or accidentally during the general use of these drugs. Many ocular side effects have been described after such intentional or accidental exposures. We describe a case of accidental ocular trauma by vinblastine. As in one of the only two previously published cases of ocular trauma by vinblastine, our patient showed acute keratopathy with a drop in visual acuity followed by the development of dry eyes and a subepithelial corneal scar. In addition, in an attempt to further evaluate the clinical course and the benefits of steroid treatment, nine rabbits were studied after ocular instillation of vinblastine. After the trauma, local steroid treatment was given in one eye of each rabbit; the second eye served as a control. The animal studies showed acute conjunctivitis and keratopathy with increasing severity in the first days and improvement thereafter. That course was similar to the one manifested in our patient. Local steroid treatment in the rabbit eye had no effect as compared with the control group. A possible mechanism for the induction of dry eyes is discussed.

Accidents, Occupational↗
PubMed1996

Upregulated expression of vascular endothelial growth factor in proliferative diabetic retinopathy.

AIMS/BACKGROUND: Vascular endothelial growth factor (VEGF) is a hypoxia induced angiogenic factor. Recent studies have shown that high levels of VEGF accumulate in the vitreous of patients with proliferative diabetic retinopathy (PDR). The purpose of the present study was to identify the retinal cells that upregulate VEGF expression in human PDR patients representing progressive stages of retina deterioration. METHODS: Thirteen formalin fixed and paraffin embedded enucleated eyes with PDR were used (eyes were enucleated because of being blind and painful as a result of neovascular glaucoma). Thin retina sections were hybridised in situ with a VEGF specific probe, to identify cells producing VEGF mRNA. RESULTS: All eyes with PDR showed upregulated expression of VEGF mRNA, specifically in the cells of the neurosensory retina. VEGF expression was upregulated in all three nuclear layers--namely, the ganglion cell layer, the inner nuclear layer, and the outer nuclear layer. However, in each patient, VEGF producing cells were mostly distributed in a different layer, or even confined to a specific region in that layer. For example, expression by the outer nuclear layer was mostly detected in detached (presumably hypoxic) regions of the retina. CONCLUSIONS: Progression of PDR is distinguished by a sustained, upregulated expression of VEGF by the neurosensory retina. Cells in all retina layers can potentially contribute to augmented VEGF production. The restricted population of VEGF producing cells in each case is likely to represent cells residing in ischaemic regions of the retina. Thus, VEGF may function as a linking factor between retinal ischaemia and PDR associated neovascularisation.

Adult↗
PubMed1996

Roles of vascular endothelial growth factor and astrocyte degeneration in the genesis of retinopathy of prematurity.

PURPOSE: To assess the role of vascular endothelial growth factor (VEGF) in the feline model of retinopathy of prematurity (ROP). METHODS: Retinopathy of prematurity was induced in neonatal cats by raising them in an oxygen-enriched (70% to 80%) atmosphere for 4 days to suppress vessel formation and then returning them to room air for 3 to 27 days. In situ hybridization was used to detect the expression of VEGF and its high-affinity receptor, flk-1, in the retina of neonatal cats, and glial fibrillary acidic protein immunocytochemistry was used to assess astrocyte status. RESULTS: The expression of VEGF in the innermost layers of retina fell in hyperoxia and increased on return to room air. Vascular endothelial growth factor expression was transient; it was maximal where vessels were about to form, and it rapidly downregulated after vessels had formed. During the proliferative vasculopathy of ROP, VEGF expression was stronger than in the normally developing retina, and the astrocytes that normally express VEGF degenerated. After the degeneration of astrocytes, VEGF was expressed by neurones of the ganglion cell layer. flk-1 was expressed by intraretinal and preretinal vessels. Supplemental oxygen therapy reduced or eliminated the overexpression of VEGF expression, astrocyte degeneration, and formation of preretinal vessels. CONCLUSIONS: Regulation of VEGF by tissue oxygen mediates the inhibition of vessel growth during hyperoxia and the subsequent proliferative vasculopathy. Degeneration of retinal astrocytes creates conditions for the growth of preretinal vessels.

Animals↗