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1. Schlötzer-Schrehardt U, Viestenz A, Naumann GO, Laqua H, Michels S, Schmidt-Erfurth U: Dose-related structural effects of photodynamic therapy on choroidal and retinal structures of human eyes. Graefes Arch Clin Exp Ophthalmol; 2002 Sep;240(9):748-57
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  • [Title] Dose-related structural effects of photodynamic therapy on choroidal and retinal structures of human eyes.
  • PURPOSE: To determine the effects of photodynamic therapy (PDT) on choroidal and retinal structures of human eyes.
  • METHODS: One eye from each of three patients with large malignant melanomas of the uvea destined for enucleation received PDT using verteporfin according to the approved treatment recommendations for patients with age-related macular degeneration.
  • RESULTS: In agreement with the clinical angiographic findings of hypofluorescence, a rather selective occlusion of the choriocapillary layer was observed in the 50-J/cm(2) PDT areas, whereas the 100-J/cm(2) PDT areas additionally revealed closure of deeper choroidal vessels and focal alterations of the retinal pigment epithelium.
  • The overlying neurosensory retina, including photoreceptors and retinal capillaries, was well preserved in all PDT areas.
  • CONCLUSIONS: PDT with verteporfin at a dosage used clinically induces selective occlusion of the physiological choriocapillaris without affecting deeper choroidal, retinal, and optic nerve vessels or the overlying retinal pigment epithelium and neurosensory retina.
  • An increase in light dose enhances the occlusive effect with thrombosis within deeper choroidal layers and damage to the retinal pigment epithelium.
  • [MeSH-major] Choroid / drug effects. Melanoma / drug therapy. Photochemotherapy. Photosensitizing Agents / therapeutic use. Porphyrins / therapeutic use. Retina / drug effects. Uveal Neoplasms / drug therapy
  • [MeSH-minor] Aged. Aged, 80 and over. Arterial Occlusive Diseases / chemically induced. Arterial Occlusive Diseases / pathology. Capillaries / drug effects. Capillaries / ultrastructure. Female. Fluorescein Angiography. Humans. Indocyanine Green. Male. Prospective Studies. Retinal Vessels / drug effects. Retinal Vessels / ultrastructure

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  • (PMID = 12271373.001).
  • [ISSN] 0721-832X
  • [Journal-full-title] Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie
  • [ISO-abbreviation] Graefes Arch. Clin. Exp. Ophthalmol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Photosensitizing Agents; 0 / Porphyrins; 129497-78-5 / verteporfin; IX6J1063HV / Indocyanine Green
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2. Lane AM, Egan KM, Harmon D, Holbrook A, Munzenrider JE, Gragoudas ES: Adjuvant interferon therapy for patients with uveal melanoma at high risk of metastasis. Ophthalmology; 2009 Nov;116(11):2206-12
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  • [Title] Adjuvant interferon therapy for patients with uveal melanoma at high risk of metastasis.
  • PURPOSE: To examine whether interferon (IFN)-alfa-2a treatment after radiation or enucleation reduces death rates in patients with uveal melanoma.
  • METHODS: Between May 1995 and June 1999, 121 patients with choroidal or ciliary body melanoma began a 2-year course of therapy (3 MIU IFN-alfa-2a subcutaneously 3 times per week), initiated within 3 years of primary therapy.
  • All patients underwent regular monitoring for drug toxicity.
  • To evaluate IFN-alfa-2a efficacy, we selected a series of historical controls frequency-matched (2:1) to IFN-alfa-2a-treated patients on age (+/-5 years), LTD (+/-3 mm), gender, and survival time between primary therapy and initiation of IFN therapy.
  • MAIN OUTCOME MEASURES: Melanoma-related mortality, metastasis, IFN-related toxicities.
  • RESULTS: Fifty-five patients (45%) completed therapy; the median dose for IFN-alfa-2a-treated patients was 792 MIU (85% of the theoretic dose).
  • The median follow-up time in the IFN-alfa-2a-treated group was approximately 9 years.
  • Treatment and control groups were similar with respect to age (P = 0.78), LTD (P = 0.38), and gender (P = 1.0).
  • Of 363 patients, 108 developed metastasis under observation; 42 of these were IFN-alfa-2a-treated patients.
  • Cumulative 5-year melanoma-related death rates were 17% in the radiation or enucleation-only group, 15% in those who completed the entire IFN-alfa-2a course, and 35% in those who discontinued IFN-alfa-2a therapy.
  • In multivariate Cox regression, IFN-alfa-2a had no significant influence on melanoma-related mortality (rate ratio = 1.02, 95% confidence interval, 0.68-1.5, P = 0.91) or all-cause mortality (rate ratio = 0.84, 95% confidence interval, 0.58-1.2, P = 0.34).
  • CONCLUSIONS: Interferon-alfa-2a has no material influence on survival in patients with choroidal melanoma.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Interferon-alpha / therapeutic use. Melanoma / drug therapy. Uveal Neoplasms / drug therapy
  • [MeSH-minor] Chemotherapy, Adjuvant. Eye Enucleation. Female. Humans. Male. Middle Aged. Neoplasm Metastasis. Radiotherapy, Adjuvant. Recombinant Proteins. Risk Factors. Survival Rate. Treatment Outcome

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  • [CommentIn] Ophthalmology. 2010 Sep;117(9):1861 [20816255.001]
  • (PMID = 19744725.001).
  • [ISSN] 1549-4713
  • [Journal-full-title] Ophthalmology
  • [ISO-abbreviation] Ophthalmology
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Interferon-alpha; 0 / Recombinant Proteins; 76543-88-9 / interferon alfa-2a
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3. Risard SM, Pieramici DJ, Rabena MD: Cystoid macular edema secondary to Paclitaxel (abraxane). Retin Cases Brief Rep; 2009;3(4):383-5
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  • METHODS: A 58-year-old man with Stage 4 metastatic cutaneous melanoma presented with decreased vision and macular edema while having minimal fluorescein leakage 7 months into a course of paclitaxel chemotherapy.
  • The edema continued to worsen, and vision declined until paclitaxel therapy was discontinued.

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  • (PMID = 25389854.001).
  • [ISSN] 1935-1089
  • [Journal-full-title] Retinal cases & brief reports
  • [ISO-abbreviation] Retin Cases Brief Rep
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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4. Diebold Y, Calonge M: Applications of nanoparticles in ophthalmology. Prog Retin Eye Res; 2010 Nov;29(6):596-609
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  • Nanocarriers, such as nanoparticles, have the capacity to deliver ocular drugs to specific target sites and hold promise to revolutionize the therapy of many eye diseases.
  • One of the most important handicaps of the eye as a target organ for drugs is the presence of several barriers that impede direct and systemic drug access to the specific site of action.
  • Superficial barriers include the ocular surface epithelium and the tear film, and internal barriers include the blood-aqueous and blood-retina barriers.
  • Topical application is the preferred route for most drugs, even when the target tissues are at the back part of the eye where intraocular injections are currently the most common route of administration.
  • Direct administration using any of these two routes faces many problems related to drug bioavailability, including side effects and repeated uncomfortable treatments to achieve therapeutic drug levels.
  • In this regard, the advantages of using nanoparticles include improved topical passage of large, poorly water-soluble molecules such as glucocorticoid drugs or cyclosporine for immune-related, vision-threatening diseases.
  • Other large and unstable molecules, such as nucleic acids, delivered using nanoparticles offer promising results for gene transfer therapy in severe retinal diseases.
  • Also, nanoparticle-mediated drug delivery increases the contact time of the administered drug with its target tissue, such as in the case of brimonidine, one of the standard treatments for glaucoma, or corticosteroids used to treat autoimmune uveitis, a severe intraocular inflammatory process.
  • In addition, nanocarriers permit the non-steroidal anti-inflammatory drug indomethacin to reach inner eye structures using the transmucosal route.
  • Finally, nanoparticles allow the possibility of targeted delivery to reach specific types of cancer, such as melanoma, leaving normal cells untouched.
  • This review summarizes experimental results from our group and others since the beginnings of nanocarrier technology to deliver drugs to different locations in the eye.
  • Also, it explores the future possibilities of nanoparticles not only as drug delivery systems but also as aides for diagnostic purposes.
  • [MeSH-major] Nanoparticles / therapeutic use. Ophthalmology. Retinal Diseases / therapy
  • [MeSH-minor] Animals. Drug Delivery Systems / methods. Humans

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  • [Copyright] Copyright © 2010 Elsevier Ltd. All rights reserved.
  • (PMID = 20826225.001).
  • [ISSN] 1873-1635
  • [Journal-full-title] Progress in retinal and eye research
  • [ISO-abbreviation] Prog Retin Eye Res
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] England
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5. Coutts MA, Borthwick NJ, Hungerford JL, Cree IA: Post-menopausal bleeding: a rare presentation of metastatic uveal melanoma. Pathol Oncol Res; 2006;12(3):184-7
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  • [Title] Post-menopausal bleeding: a rare presentation of metastatic uveal melanoma.
  • Uveal melanoma differs from cutaneous melanoma in many ways, including its pattern of metastasis, and exhibits latency with clinical evidence of metastasis sometimes appearing many years after primary diagnosis.
  • We report a case of uveal melanoma that presented with post-menopausal bleeding due to metastasis.
  • Further investigation revealed widespread metastatic disease and the patient was not fit for chemotherapy.
  • The immediate cause of death was cardiac tamponade due to a malignant effusion secondary to cardiac metastasis.
  • This case illustrates the widespread metastatic potential of uveal melanoma and highlights the potential for unusual presentation of metastatic disease from this eye tumor.
  • [MeSH-major] Melanoma / pathology. Uterine Hemorrhage / etiology. Uveal Neoplasms / pathology
  • [MeSH-minor] Aged, 80 and over. Endometrial Neoplasms / secondary. Female. Heart Neoplasms / secondary. Humans. Liver Neoplasms / secondary. Neoplasm Metastasis. Postmenopause

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6. Sithanandam G, Anderson LM: The ERBB3 receptor in cancer and cancer gene therapy. Cancer Gene Ther; 2008 Jul;15(7):413-48
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  • [Title] The ERBB3 receptor in cancer and cancer gene therapy.
  • Studies of ERBB3 expression in primary cancers and of its mechanistic contributions in cultured cells have implicated it, with varying degrees of certainty, with causation or sustenance of cancers of the breast, ovary, prostate, certain brain cells, retina, melanocytes, colon, pancreas, stomach, oral cavity and lung.
  • Recent results link high ERBB3 activity with escape from therapy targeting other ERBBs in lung and breast cancers.
  • Small inhibitory RNA (siRNA) to ERBB3 or AKT is showing promise as a therapeutic approach to treatment of lung adenocarcinoma.

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  • (PMID = 18404164.001).
  • [ISSN] 1476-5500
  • [Journal-full-title] Cancer gene therapy
  • [ISO-abbreviation] Cancer Gene Ther.
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CO / N01 CO012400; United States / NCI NIH HHS / CA / N01CO12400; United States / Intramural NIH HHS / / Z01 BC005399-24; United States / NCI NIH HHS / CO / N01-CO-12400
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Neuregulins; 0 / RNA, Small Interfering; EC 2.7.10.1 / Receptor, ErbB-3
  • [Number-of-references] 438
  • [Other-IDs] NLM/ NIHMS107476; NLM/ PMC2761714
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7. Bishop RJ, Ding X, Heller CK 3rd, Illei G, Caruso R, Cunningham D, Pavletic S, Chan CC: Rapid vision loss associated with fludarabine administration. Retina; 2010 Sep;30(8):1272-7
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  • RESULTS: A 23-year-old man (Case 1) with systemic lupus erythematosus developed rapid and severe vision loss, generalized neurologic decline, and eventual death after administration of fludarabine before stem cell transplantation.
  • A 48-year-old woman (Case 2) and a 60-year-old man (Case 3), both with metastatic melanoma, had similar courses after receiving fludarabine as part of a preparatory regimen before adoptive cell therapy.
  • In all three cases, serum antiretinal antibodies were negative before and after treatment; electrophysiological testing showed markedly decreased B-waves; and pathologic analysis showed loss of retinal bipolar and ganglion cells, gliosis within the retina and optic nerve, and optic nerve atrophy.
  • CONCLUSION: Fludarabine toxicity can result in severe vision loss attributable to damage to retinal bipolar and ganglion cells.
  • Although effective treatments are not known, care should be taken to consider fludarabine toxicity in patients who present with vision loss approximately 1 month after treatment.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Blindness / chemically induced. Retinal Diseases / chemically induced. Vidarabine / analogs & derivatives
  • [MeSH-minor] Brain Diseases / chemically induced. Brain Diseases / diagnosis. Electroretinography. Evoked Potentials, Visual. Fatal Outcome. Female. Humans. Lupus Erythematosus, Systemic / drug therapy. Magnetic Resonance Imaging. Male. Melanoma / drug therapy. Melanoma / secondary. Middle Aged. Myeloablative Agonists / adverse effects. Retina / drug effects. Retina / physiopathology. Retrospective Studies. Young Adult

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  • (PMID = 20224467.001).
  • [ISSN] 1539-2864
  • [Journal-full-title] Retina (Philadelphia, Pa.)
  • [ISO-abbreviation] Retina (Philadelphia, Pa.)
  • [Language] eng
  • [Grant] United States / Intramural NIH HHS / / ZIA EY000222-24; United States / Intramural NIH HHS / / ZIA EY000222-25
  • [Publication-type] Case Reports; Journal Article; Research Support, N.I.H., Intramural
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Myeloablative Agonists; FA2DM6879K / Vidarabine; P2K93U8740 / fludarabine
  • [Other-IDs] NLM/ NIHMS227991; NLM/ PMC2943138
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8. Freudenstein D, Wagner A, Bornemann A, Ernemann U, Bauer T, Duffner F: Primary melanocytic lesions of the CNS: report of five cases. Zentralbl Neurochir; 2004;65(3):146-53
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  • Primary melanocytic tumours of the central nervous system (CNS) form a rare entity which is histologically and clinically distinct from metastatic cutaneous or retinal malignant melanoma.
  • They can be classified into diffuse melanocytosis (diffuse melanosis), malignant melanoma and benign melanocytoma with a small number of intermediate variants.
  • In this paper, 5 cases treated neurosurgically in our department for spinal or cerebral primary CNS malignant melanoma are reported.
  • Compared to metastatic disease, primary CNS malignant melanoma shows a more benign clinical course with long-term tumour control and a good quality of life.
  • Although therapeutic experience for primary melanocytic lesions of the CNS is based on a small number of published cases, prognosis seems highly dependent on complete tumour resection.
  • Adjuvant radiation seems to be of additional therapeutic benefit.
  • Except for meningeosis melanomatosa chemotherapy must be regarded as experimental.
  • Unfortunately, a standardised therapy concept is still lacking.
  • [MeSH-major] Brain Neoplasms / surgery. Melanocytes / pathology. Melanoma / surgery. Neurosurgical Procedures. Spinal Neoplasms / surgery
  • [MeSH-minor] Adult. Aged. Combined Modality Therapy. Fatal Outcome. Female. Humans. Magnetic Resonance Imaging. Male. Middle Aged. Quality of Life. Treatment Outcome

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  • (PMID = 15306980.001).
  • [ISSN] 0044-4251
  • [Journal-full-title] Zentralblatt für Neurochirurgie
  • [ISO-abbreviation] Zentralbl. Neurochir.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
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9. Di Nicolantonio F, Neale M, Onadim Z, Hungerford JL, Kingston JL, Cree IA: The chemosensitivity profile of retinoblastoma. Recent Results Cancer Res; 2003;161:73-80
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  • Retinoblastoma is a rare malignant tumour of the developing retina with an incidence of 1 in 20,000 live births in all human races.
  • Chemotherapy is used in retinoblastoma as adjuvant therapy to prevent the growth of metastases and to treat metastatic disease once this has become clinically apparent.
  • Current regimens are based on empirical drug combinations, and few clinical trials have been conducted because of the rarity of this tumour.
  • The ATP-based chemosensitivity assay (ATP-TCA) has already helped to design new regimens for melanoma and breast and ovarian cancer.
  • These data confirm that retinoblastoma is a rapidly growing malignancy that is very susceptible to cytotoxic drugs of all types.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Drug Screening Assays, Antitumor / methods. Retinal Neoplasms / drug therapy. Retinoblastoma / drug therapy
  • [MeSH-minor] Adenosine Triphosphate / metabolism. Child, Preschool. Drug Resistance, Neoplasm. Female. Humans. Infant. Male. Tumor Cells, Cultured / drug effects

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  • (PMID = 12528800.001).
  • [ISSN] 0080-0015
  • [Journal-full-title] Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer
  • [ISO-abbreviation] Recent Results Cancer Res.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 8L70Q75FXE / Adenosine Triphosphate
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10. Schmidt-Erfurth U, Laqua H, Schlötzer-Schrehard U, Viestenz A, Naumann GO: Histopathological changes following photodynamic therapy in human eyes. Arch Ophthalmol; 2002 Jun;120(6):835-44
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  • [Title] Histopathological changes following photodynamic therapy in human eyes.
  • [MeSH-major] Choroid / pathology. Photochemotherapy. Photosensitizing Agents / therapeutic use. Pigment Epithelium of Eye / pathology. Porphyrins / therapeutic use. Retina / pathology
  • [MeSH-minor] Aged. Aged, 80 and over. Choroidal Neovascularization / drug therapy. Choroidal Neovascularization / pathology. Endothelium, Vascular / pathology. Endothelium, Vascular / ultrastructure. Eye Enucleation. Female. Fluorescein Angiography. Humans. Indocyanine Green. Macular Degeneration / drug therapy. Macular Degeneration / pathology. Male. Melanoma / surgery. Retinal Vessels / pathology. Retinal Vessels / ultrastructure. Uveal Neoplasms / surgery

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  • (PMID = 12049594.001).
  • [ISSN] 0003-9950
  • [Journal-full-title] Archives of ophthalmology (Chicago, Ill. : 1960)
  • [ISO-abbreviation] Arch. Ophthalmol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Photosensitizing Agents; 0 / Porphyrins; 129497-78-5 / verteporfin; IX6J1063HV / Indocyanine Green
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11. Lederman M, Meir T, Zeschnigk M, Pe'er J, Chowers I: Inhibitor of apoptosis proteins gene expression and its correlation with prognostic factors in primary and metastatic uveal melanoma. Curr Eye Res; 2008 Oct;33(10):876-84
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  • [Title] Inhibitor of apoptosis proteins gene expression and its correlation with prognostic factors in primary and metastatic uveal melanoma.
  • PURPOSE: Members of the inhibitors of apoptosis proteins (IAPs) family are thought to promote tumor growth and interfere with response to therapy by suppressing apoptosis in several malignancies.
  • We aimed to evaluate the expression of IAPs in uveal melanoma (UM) and its correlation with prognostic factors associated with death from metastatic UM.
  • QPCR results were correlated with apoptosis rate and with prognostic factors in UM, including lesion dimensions, cell type, monosomy 3, and vascular mimicry patterns.
  • BIRC5 and BIRC7 levels were 8.8-fold (p = 0.0003) and 7.0-fold (p = 0.003) higher in tumors (primary and metastatic tissue) vs. normal eye tissue, respectively.
  • BIRC5 levels correlated with presence of monosomy 3 (p = 0.01) and higher levels of BIRC7 correlated with epithelioid cell type (p = 0.048).
  • Considering our findings together with previous reports on their role in a variety of malignancies and in UM cell lines, it is conceivable that IAPs contribute to the remarkable resistance of uveal melanoma to apoptosis-inducing chemotherapy.
  • [MeSH-major] Gene Expression Regulation, Neoplastic. Inhibitor of Apoptosis Proteins / genetics. Liver Neoplasms / genetics. Melanoma / genetics. Uveal Neoplasms / genetics
  • [MeSH-minor] Adult. Aged. Aged, 80 and over. Apoptosis / genetics. Cell Line, Tumor. Choroid / metabolism. Chromosome Aberrations. Chromosomes, Human, Pair 3 / genetics. Female. Humans. Immunohistochemistry. Male. Middle Aged. Prognosis. Retina / metabolism. Reverse Transcriptase Polymerase Chain Reaction. Up-Regulation

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  • (PMID = 18853322.001).
  • [ISSN] 1460-2202
  • [Journal-full-title] Current eye research
  • [ISO-abbreviation] Curr. Eye Res.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Inhibitor of Apoptosis Proteins
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12. Dawson WW, Jordan BL, Marsh RD, Hazariwala K, Flowers FP, Fang T: Distant cancer effects on standardised testing of peripheral vision. Br J Ophthalmol; 2001 Mar;85(3):291-6
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  • BACKGROUND: Profound central-retinal visual losses have been a major presenting factor reported in cancer and melanoma associated retinopathies (CAR, MAR).
  • However, it is well established that standardised tests of peripheral retinal function are often the most sensitive detectors of early eye disease.
  • This is a preliminary investigation of the responsiveness of the peripheral retina to "distant" (non-eye or CNS) cancers using easily obtained standardised tests.
  • RESULTS: 98% (49 of 50) of eyes from the patient cohort were judged clinically normal following examinations which emphasised the central retina, fundus appearance, and static fields.
  • These abnormalities clustered mainly about dark adaptation (rod cell) sensitivity (31, 62% of measured sites), the blue sensitive retinal cells (17, 34% of measured eyes), and the oscillatory component (OP) of the electroretinogram (23, 46% of measured eyes).
  • There was no identifiable interaction between chemotherapy mode and the cancer associated retinal deficits (CARD).
  • CONCLUSION: CARD is common in the retinal periphery of many cancer patients, and is distinct from rare CAR, MAR central-retinal responses.
  • [MeSH-major] Breast Neoplasms / complications. Lung Neoplasms / complications. Melanoma / complications. Vision, Low / etiology
  • [MeSH-minor] Adaptation, Ocular / physiology. Adult. Aged. Analysis of Variance. Antineoplastic Agents / therapeutic use. Autoantibodies / blood. Case-Control Studies. Color Perception Tests. Electroretinography. Female. Humans. Male. Middle Aged. Reference Values. Retina / immunology. Single-Blind Method. Visual Acuity. Visual Field Tests

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  • (PMID = 11222333.001).
  • [ISSN] 0007-1161
  • [Journal-full-title] The British journal of ophthalmology
  • [ISO-abbreviation] Br J Ophthalmol
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Autoantibodies
  • [Other-IDs] NLM/ PMC1723897
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13. Jacobson DM, Adamus G: Retinal anti-bipolar cell antibodies in a patient with paraneoplastic retinopathy and colon carcinoma. Am J Ophthalmol; 2001 Jun;131(6):806-8
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  • [Title] Retinal anti-bipolar cell antibodies in a patient with paraneoplastic retinopathy and colon carcinoma.
  • PURPOSE: To describe clinical, electrophysiologic, and immunologic features of a unique paraneoplastic retinopathy with characteristics of cancer-associated and melanoma-associated retinopathy.
  • METHODS: Serial assessment of clinical visual function, electroretinography, and assays of anti-retinal antibodies.
  • RESULTS: A 51-year-old woman with progressive visual glare for 1 year had normal visual acuity and color vision, paracentral scotomas, and a normal-appearing retina.
  • Several months after resection of the tumor and chemotherapy, no evidence existed of cancer or anti-bipolar cell antibodies, and electroretinography responses were markedly improved.
  • CONCLUSION: The presence of anti-bipolar cell antibodies in a patient with retinal dysfunction is not specific of melanoma-associated retinopathy.
  • Effective treatment of cancer may result in elimination of associated anti-retinal antibodies and improved retinal function.

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  • (PMID = 11384586.001).
  • [ISSN] 0002-9394
  • [Journal-full-title] American journal of ophthalmology
  • [ISO-abbreviation] Am. J. Ophthalmol.
  • [Language] ENG
  • [Grant] United States / NEI NIH HHS / EY / R01 EY013053; United States / NEI NIH HHS / EY / EY 13053
  • [Publication-type] Case Reports; Journal Article; Research Support, U.S. Gov't, P.H.S.
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Autoantibodies
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14. Querques G, Prascina F, Iaculli C, Delle Noci N: Intravitreal pegaptanib sodium (Macugen) for radiation retinopathy following episcleral plaque radiotherapy. Acta Ophthalmol; 2008 Sep;86(6):700-1
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  • [MeSH-major] Aptamers, Nucleotide / therapeutic use. Brachytherapy / adverse effects. Optic Disk / blood supply. Radiation Injuries / drug therapy. Retina / radiation effects. Retinal Neovascularization / drug therapy
  • [MeSH-minor] Choroid Neoplasms / radiotherapy. Exudates and Transudates. Female. Fluorescein Angiography. Humans. Injections. Melanoma / radiotherapy. Middle Aged. Retinal Hemorrhage / diagnosis. Retinal Hemorrhage / drug therapy. Retinal Hemorrhage / etiology. Tomography, Optical Coherence. Vascular Endothelial Growth Factor A / antagonists & inhibitors. Vitreous Body

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  • (PMID = 18705681.001).
  • [ISSN] 1755-3768
  • [Journal-full-title] Acta ophthalmologica
  • [ISO-abbreviation] Acta Ophthalmol
  • [Language] eng
  • [Publication-type] Case Reports; Letter
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Aptamers, Nucleotide; 0 / Vascular Endothelial Growth Factor A; 0 / pegaptanib
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15. Dunavoelgyi R, Zehetmayer M, Simader C, Schmidt-Erfurth U: Rapid improvement of radiation-induced neovascular glaucoma and exudative retinal detachment after a single intravitreal ranibizumab injection. Clin Exp Ophthalmol; 2007 Dec;35(9):878-80
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Rapid improvement of radiation-induced neovascular glaucoma and exudative retinal detachment after a single intravitreal ranibizumab injection.
  • Neovascular glaucoma is a serious complication arising from irradiation of uveal melanoma.
  • Treatment options include panretinal photocoagulation, peripheral retina cryotherapy, photodynamic therapy with verteporfin, triamcinolone injections and surgical removal of the dying tumour mass.
  • The authors describe a case report of a radiation-induced neovascular glaucoma and exudative retinal detachment caused by malignant melanoma of the uvea that was treated with intravitreal ranibizumab.
  • [MeSH-major] Antibodies, Monoclonal / administration & dosage. Exudates and Transudates / metabolism. Glaucoma, Neovascular / drug therapy. Glaucoma, Neovascular / etiology. Radiation Injuries / complications. Retinal Detachment / drug therapy. Retinal Detachment / etiology
  • [MeSH-minor] Aged. Antibodies, Monoclonal, Humanized. Drug Administration Schedule. Humans. Injections. Ranibizumab. Vitreous Body

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  • (PMID = 18173426.001).
  • [ISSN] 1442-9071
  • [Journal-full-title] Clinical & experimental ophthalmology
  • [ISO-abbreviation] Clin. Experiment. Ophthalmol.
  • [Language] eng
  • [Publication-type] Case Reports; Letter
  • [Publication-country] Australia
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Humanized; ZL1R02VT79 / Ranibizumab
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16. Cantrill HL, Pulido JS, Donaldson M, Shields CL, Murray TG: Diagnostic and therapeutic challenges. Retina; 2008 Jul-Aug;28(7):1018-22
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Diagnostic and therapeutic challenges.
  • [MeSH-major] Choroid Neoplasms / ultrasonography. Melanoma / ultrasonography
  • [MeSH-minor] Aged. Antibodies, Monoclonal / therapeutic use. Antibodies, Monoclonal, Murine-Derived. Antineoplastic Agents / therapeutic use. Eye Enucleation. Female. Fluorescein Angiography. Humans. Lymphatic Metastasis. Lymphoma, B-Cell, Marginal Zone / drug therapy. Lymphoma, B-Cell, Marginal Zone / pathology. Parotid Neoplasms / drug therapy. Parotid Neoplasms / pathology. Rituximab

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  • (PMID = 18698308.001).
  • [ISSN] 0275-004X
  • [Journal-full-title] Retina (Philadelphia, Pa.)
  • [ISO-abbreviation] Retina (Philadelphia, Pa.)
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antibodies, Monoclonal; 0 / Antibodies, Monoclonal, Murine-Derived; 0 / Antineoplastic Agents; 4F4X42SYQ6 / Rituximab
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17. De Potter P, Disneur D, Levecq L, Snyers B: [Ocular manifestations of cancer]. J Fr Ophtalmol; 2002 Feb;25(2):194-202
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  • [Transliterated title] Manifestations oculaires des cancers.
  • Cancer may affect the eye and orbit as a direct result of metastatic neoplastic infiltration, compression, or circulating antibodies involving paraneoplastic retinal degeneration.
  • The choroid is the most common site for uveal metastasis; metastases to the ciliary body, iris, retina, optic disk, and vitreous are rare.
  • Approximately one-third of patients have no history of primary cancer at the time of ocular diagnosis.
  • The short-term prognosis for vision is usually good after an individualized therapeutic approach (chemotherapy, hormonal therapy, external beam radiotherapy, or plaque radiotherapy), but the systemic prognosis is poor.
  • The visual paraneoplastic syndromes encompass several distinct clinical and pathological entities including carcinoma-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), and bilateral diffuse melanocytic uveal proliferation (BDUMP).
  • Identification of circulating antibodies against retinal proteins (recovering, 23-kDa retinal protein; 46-kDa and 60-kDa retinal proteins) serves to recognize the paraneoplastic nature of the patient's symptoms, which frequently develop before the cancer is diagnosed.
  • Anecdotal therapeutic responses are described after systemic steroids, immunoglobulin injection, and plasmapheresis.
  • [MeSH-major] Eye Neoplasms / secondary. Lymphoma / diagnosis. Paraneoplastic Syndromes
  • [MeSH-minor] Adult. Child. Choroid Neoplasms / diagnosis. Choroid Neoplasms / secondary. Diagnosis, Differential. Eyelid Neoplasms / diagnosis. Eyelid Neoplasms / secondary. Female. Humans. Iris Neoplasms / diagnosis. Iris Neoplasms / secondary. Lymphoma, Non-Hodgkin / diagnosis. Male. Melanoma / complications. Melanoma / diagnosis. Melanoma / secondary. Orbital Neoplasms / diagnosis. Orbital Neoplasms / secondary. Prognosis. Retinal Diseases / etiology. Retinal Neoplasms / diagnosis. Retinal Neoplasms / secondary. Visual Acuity. Vitreous Body

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  • (PMID = 11941243.001).
  • [ISSN] 0181-5512
  • [Journal-full-title] Journal français d'ophtalmologie
  • [ISO-abbreviation] J Fr Ophtalmol
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] France
  • [Number-of-references] 103
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18. Subhadra C, Dudek AZ, Rath PP, Lee MS: Improvement in visual fields in a patient with melanoma-associated retinopathy treated with intravenous immunoglobulin. J Neuroophthalmol; 2008 Mar;28(1):23-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Improvement in visual fields in a patient with melanoma-associated retinopathy treated with intravenous immunoglobulin.
  • Melanoma-associated retinopathy (MAR) is a rare disorder characterized by photopsias, shimmering vision, nyctalopia, and dysfunction of rod photoreceptor cells.
  • We describe a 56-year-old man with metastatic cutaneous melanoma to the lymph nodes and MAR.
  • He underwent resection of the metastasis followed by radiation therapy.
  • Our patient indicates that even after a reduction or elimination of melanoma tumor burden and presumably the attenuation of the antigenic stimulus driving MAR, this disorder can continue to progress.
  • In this setting, IVIg therapy should be considered a viable treatment option.
  • [MeSH-major] Immunoglobulins, Intravenous / administration & dosage. Melanoma / complications. Paraneoplastic Syndromes, Nervous System / drug therapy. Paraneoplastic Syndromes, Nervous System / physiopathology. Retinal Diseases / drug therapy. Retinal Diseases / physiopathology
  • [MeSH-minor] Autoantibodies / drug effects. Autoantibodies / immunology. Disease Progression. Electroretinography. Humans. Immunotherapy / methods. Lymph Nodes / pathology. Lymph Nodes / surgery. Male. Middle Aged. Neck Dissection. Neoplasm Recurrence, Local / radiotherapy. Neoplasm Recurrence, Local / surgery. Radiotherapy. Retina / drug effects. Retina / immunology. Retina / physiopathology. Retinal Bipolar Cells / drug effects. Retinal Bipolar Cells / immunology. Retinal Bipolar Cells / pathology. Treatment Outcome. Vision, Low / drug therapy. Vision, Low / immunology. Vision, Low / physiopathology. Visual Fields / drug effects. Visual Fields / immunology

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  • (PMID = 18347454.001).
  • [ISSN] 1536-5166
  • [Journal-full-title] Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society
  • [ISO-abbreviation] J Neuroophthalmol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Autoantibodies; 0 / Immunoglobulins, Intravenous
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19. Hartmann TB, Bazhin AV, Schadendorf D, Eichmüller SB: SEREX identification of new tumor antigens linked to melanoma-associated retinopathy. Int J Cancer; 2005 Mar 10;114(1):88-93
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] SEREX identification of new tumor antigens linked to melanoma-associated retinopathy.
  • Metastatic melanoma still has a very poor prognosis since it withstands conventional therapies like surgery or chemotherapy.
  • A paraneoplastic autoimmune manifestation of this disease is melanoma-associated retinopathy (MAR).
  • By screening a retina and a melanoma cDNA phage library by SEREX using sera of patients suffering from melanoma and, in some cases, clinical symptoms of MAR, we identified 20 new antigens (HD-MM-28-47), of which 14 clones had high homology to well-known genes.
  • Six of these genes had previously been associated with retina: rhodopsin, visual arrestin, MEK1, SRPX, BBS1 and galectin-3.
  • The expression profile of the antigens identified on the basis of homologous EST database entries in healthy tissues was ubiquitous to differential.
  • Using RT-PCR, we found frequent expression of preselected antigens in melanoma cell lines.
  • Retinal proteins were recognized by serum antibodies of melanoma patients but not healthy controls.
  • [MeSH-major] Antigens, Neoplasm / analysis. Melanoma / immunology. Paraneoplastic Syndromes / immunology. Retinal Diseases / immunology. Serologic Tests / methods. Skin Neoplasms / immunology
  • [MeSH-minor] Blotting, Northern. Cell Line, Tumor. DNA, Complementary / analysis. DNA, Neoplasm / analysis. Gene Library. Humans. RNA, Neoplasm / analysis. Reverse Transcriptase Polymerase Chain Reaction. Rhodopsin / immunology


20. Zubilewicz A, Hecquet C, Jeanny JC, Soubrane G, Courtois Y, Mascarelli F: Two distinct signalling pathways are involved in FGF2-stimulated proliferation of choriocapillary endothelial cells: a comparative study with VEGF. Oncogene; 2001 Mar 22;20(12):1403-13
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  • In the retina, angiogenesis is an important component of normal physiological events such as embryonic vascular development.
  • It is also involved in pathological processes including diabetic retinopathies and age-related macular degeneration, and tumour growth such as choroidal melanoma.
  • Fibroblast growth factor (FGF) 2 and vascular endothelial cell growth factor (VEGF) are the two major angiogenic factors in the retina.
  • Pharmacological inhibition of Ras processing, and of MEK1 and ERK1/2 activation reduced only by 50% FGF2-induced cell proliferation, suggesting that there is another signalling pathway for CEC proliferation.
  • Pharmacological inhibition of the PI 3-Kinase also inhibits by half FGF2-induced CEC proliferation.
  • These data on the molecular mechanism and signalling may have important implications for providing more selective methods for anti-angiogenic and anti-tumoural therapy.
  • [MeSH-minor] Animals. Cattle. Cell Division. Dose-Response Relationship, Drug. Immunomagnetic Separation. Mitogen-Activated Protein Kinase 1. Mitogen-Activated Protein Kinase 3. Mitogen-Activated Protein Kinases / metabolism. Mitogens / pharmacology. Models, Biological. Neovascularization, Physiologic. Phosphatidylinositol 3-Kinases / metabolism. Receptor Cross-Talk. Vascular Endothelial Growth Factor A. Vascular Endothelial Growth Factors


21. Jacobzone C, Cochard-Marianowski C, Kupfer I, Bettembourg S, Dordain Y, Misery L, Cochener B, Sassolas B: Corticosteroid treatment for melanoma-associated retinopathy: effect on visual acuity and electrophysiologic findings. Arch Dermatol; 2004 Oct;140(10):1258-61
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  • [Title] Corticosteroid treatment for melanoma-associated retinopathy: effect on visual acuity and electrophysiologic findings.
  • BACKGROUND: Visual disturbance in the course of melanoma is rare.
  • Specific localized metastases and drug toxic effects are frequently the cause.
  • Recognition of a retinopathy raises several questions when the diagnosis of melanoma-associated retinopathy (MAR) can be confirmed.
  • Descriptions of such patients in dermatologic literature are rare and deserve attention because therapeutic decisions are mandatory.
  • OBSERVATIONS: A 70-year-old woman had a first melanoma in 1985 and a second primary melanoma in 1994.
  • Axillary lymph node involvement occurred in November 2000, leading to surgery and chemotherapy.
  • Computed tomography and cerebral magnetic resonance imaging ruled out localized tumor on the eyes or optic nerves or evolution of disease.
  • Ophthalmologic examination revealed a bilateral posterior uveitis, with hyalitis and progressive destruction of retinal pigment.
  • The electrophysiologic data confirmed the diagnosis of MAR.
  • Symptoms improved after systemic corticosteroid therapy, with no relapse after tapering doses despite worsening of melanoma.
  • Also, MAR is linked to the presence of autoantibodies directed against melanoma antigens that cross-react with the rod bipolar cells of the retina.
  • Corticosteroid therapy is rarely beneficial.
  • Our case of MAR is noteworthy because it involved a woman, was associated with an uveitis, and improved with corticosteroid therapy.
  • [MeSH-major] Adrenal Cortex Hormones / therapeutic use. Melanoma / complications. Retinal Diseases / diagnosis. Retinal Diseases / drug therapy. Skin Neoplasms / complications
  • [MeSH-minor] Aged. Diagnosis, Differential. Electrophysiology. Female. Humans. Neoplasms, Second Primary / complications. Paraneoplastic Syndromes / diagnosis. Paraneoplastic Syndromes / drug therapy. Paraneoplastic Syndromes / etiology. Vision, Low / diagnosis. Vision, Low / drug therapy. Vision, Low / etiology. Visual Acuity

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  • (PMID = 15492190.001).
  • [ISSN] 0003-987X
  • [Journal-full-title] Archives of dermatology
  • [ISO-abbreviation] Arch Dermatol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Adrenal Cortex Hormones
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