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PubMed2004

The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma.

Recently, there has been increasing interest in treating intraocular retinoblastoma with systemic chemotherapy combined with focal laser therapy and cryotherapy instead of radiotherapy. We developed a system of selective ophthalmic arterial infusion (SOAI) therapy, administering melphalan, the agent which had the greatest effect on retinoblastoma in a clonogenic assay. The SOAI system consists of a combination of a micro-balloon, a guiding catheter, and a flushing hub. After selective catheterization to the cervical segment of the internal carotid artery by the guiding catheter, the micro-balloon was propelled to the portion just distal to the orifice of the ophthalmic artery. During temporary occlusion of the internal carotid artery, melphalan was infused from the introduced catheter tip. We treated 187 patients with intraocular retinoblastoma with SOAI; 563 SOAIs were performed for 610 eyes. The technical success rate was 97.51%. Fourteen examinations failed. No significant complication due to catheterization (including brain infarction) was detected. SOAI, using the balloon occlusion technique, is safe, and its use will prevent the side effects that occur with systemic chemotherapy, and eliminate the need for irradiation and enucleation.

Antineoplastic Agents, Alkylating↗
PubMedDate not supplied

Inhibition of histone deacetylation by butyrate induces morphological changes in Y79 retinoblastoma cells.

PURPOSE: Exposure of Y79 cells, a retinoblastoma cell line, to sodium butyrate, a histone deacetylase inhibitor, induces neuronlike morphological changes and apoptosis. To determine whether the effect of butyrate results from an inhibition of histone deacetylation, we examined the morphological changes, cell viability, and histone acetylation levels of Y79 cells induced by butyrate and trichostatin A (TSA), a specific inhibitor of histone deacetylases. METHODS: Y79 cells cultured in a synthetic medium were exposed to butyrate or TSA, and the morphological changes and cell viability were followed. Actinomycin D was used to determine whether the morphological changes were transcription-dependent. The level of acetylated histone was determined by Western blotting and immunocytochemistry. RESULTS: Butyrate and TSA induced morphological changes and apoptosis of Y79 retinoblastoma cells in a dose-dependent manner. The morphological changes were sustained and reversible with butyrate but were transient with TSA. Actinomycin D completely inhibited the morphological changes induced by butyrate and TSA. The elevation of histone H3 levels was sustained and reversible in butyrate but transient in TSA. The change in histone H3 acetylation levels preceded the morphological changes and apoptosis. CONCLUSION: The induction of morphological changes by butyrate results from an inhibition of histone deacetylation and transcription.

Acetylation↗
PubMed2005

Ophthalmological manifestations in VHL and NF 1: pathological and diagnostic implications.

Von Hippel-Lindau disease (VHL) and neurofibromatosis type 1 (NF 1) are hereditary multitumor syndromes that show associated ocular manifestations. Capillary retinal angioma, a benign vascular tumor, is the classical ocular lesion in VHL. It often appears as the first manifestation of the disease and may thus lead to the diagnosis of VHL. Since small angiomas can be treated easily by laser photocoagulation, a regular ocular screening of VHL patients is recommended. Ocular manifestations of NF 1 are more diverse as compared to VHL. Lisch nodules of the iris are an important diagnostic criteria of NF 1 since they can be found in almost every affected patient. Optic glioma can occur both intraorbitally and intracranially. The intraorbital form causes progressive protrusion of the globe and eventually blindness. Extension of the tumor beyond the chiasm worsens the prognosis quoad vitam. The hallmark of NF 1, namely cutaneous neurofibroma can cause visual impairment when affecting the skin of the eyelids. The rare intraorbital pexiform neurofibroma is associated with abnormal development of the orbital bones and infantile glaucoma. It may result in orbital mass effects and therefore may need surgical excision.

Hemangioma↗
PubMed2006

Unusual macular lesions in a patient with neurofibromatosis type-1.

BACKGROUND: Retinal involvement in neurofibromatosis type-1 (NF-1) is rare. METHODS: We present a case report of a 49-year-old man with neurofibromatosis who developed bilateral macular lesions associated with gradual reduction of visual acuity. RESULTS: Electrophysiology revealed an absent pattern electroretinogram. Fluorescein angiography demonstrated mottled hyperfluorescence of the maculae in the early-phase fluorescein angiogram followed by late staining of the lesions. CONCLUSIONS: Our patient had unusual bilateral macular lesions which had some features suggestive of adult-onset foveomacular vitelliform dystrophy. To the best of our knowledge, there have been no previous reports of such macular lesions occurring in association with NF-1.

Diagnosis, Differential↗
PubMed2006

Effects of shRNA targeting survivin on apoptosis of human retinoblastoma cell line Hxo-rb44 in vitro.

In order to construct a recombinant plasmid containing short hairpin RNA (shRNA) targeting survivin and to investigate its effect on survivin expression and cell apoptosis of human retinoblastoma cell line Hxo-rb44 in vitro, RNA interference plasmid pSIRENS that can express shRNA of survivin was designed, constructed, and transfected into human retinoblastoma cell line Hxo-rb44. Survivin and c-Myc expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. Apoptosis of Hxo-rb44 cells was assayed by Honchest33258 staining and cell growth curve was drawn. The results showed that the oligonucleotide targeting survivin was identified in pSIRENS plasmid. After pSIRENS plasmid transfected, survivin and c-Myc expression in Hxo-rb44 cells was decreased significantly. Apoptotic rate of cells was up-regulated from (3.5+/-1.29) % to (36.1+/-19.66) %. The proliferation ability of Hxo-rb44 cells was inhibited. No significant effects on survivin expression and apoptosis of the cells were found when negative control plasmid was transfected. In conclusion, the plasmid containing shRNA targeting survivin was constructed successfully. It could inhibit efficiently the expression of survivin and c-Myc in human retinoblastoma cell Hxo-rb44 in vitro. The inhibition of the expression of c-Myc might be involved in the apoptosis of Hxo-rb44 cells.

Apoptosis↗
PubMed2004

Neuro-ophthalmology of von Hippel-Lindau.

von Hippel-Lindau (VHL) disease is a multisystem inherited cancer syndrome with characteristic tumors and a known genetic basis. Patients with VHL develop, among other tumors, retinal capillary hemangiomas, central nervous system hemangioblastomas, renal clear cell carcinomas, and pheochromocytomas. Nearly all patients can be shown to have a mutation in the VHL gene, which is located on chromosome 3p25. Genetic abnormalities result in abnormal levels of pVHL, which in turn lead to the different tumors. Four distinct phenotypes of VHL disease have been identified based on the relative frequency of and propensity for the development of different VHL tumors. Aggressive screening of patients with VHL disease can prevent morbidity and mortality from these tumors. Although these tumors typically have been treated with observation or surgery, trials of newer medical therapies that target some of the cellular dysregulation caused by mutation in pVHL are ongoing. Even though these trials have not been wholly successful, they present an exciting direction for future research. This article presents a summary of new developments in VHL disease with a focus on ophthalmic and neuro-ophthalmic practice.

Adolescent↗
PubMed1966

Rationale for vitamin-B12 treatment of retinoblastoma.

Retinoblastoma and neuroblastoma have many common characteristics. There are conflicting reports of the effectiveness of vitamin B12 in the therapy of neuroblastoma. Where conventional therapy has failed in the treatment of intraocular retinoblastoma, a trial of vitamin B12 is suggested.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

Aicardi syndrome associated with an embryonal carcinoma.

A Japanese girl is reported who had the typical clinical features of Aicardi syndrome associated with embryonal carcinoma. She developed infantile spasms at approximately 4 weeks of age; her seizures were intractable in spite of treatment with numerous antiepileptic drugs and ACTH. At 22 months of age, her left cheek gradually became swollen. Laboratory findings were normal except for a marked increase in serum alpha-fetoprotein. A transoral biopsy of the tumor revealed an embryonal carcinoma. This patient is the first reported with Aicardi syndrome and embryonal carcinoma. The relationship between congenital malformations and neoplasms is discussed.

Agenesis of Corpus Callosum↗
PubMed2004

Retinal capillary angioma in familial exudative vitreoretinopathy treated with photodynamic therapy.

PURPOSE: To report a case of familial exudative vitreoretinopathy with a retinal capillary angioma and persistent macular exudation treated with photodynamic therapy. DESIGN: Interventional case report. METHODS: A 39-year-old woman with familial exudative vitreoretinopathy presented with an intraretinal capillary angioma temporally with persistent macular exudation despite previous vitrectomy and thermal laser. Photodynamic therapy to the retinal angioma was performed. RESULTS: Three months after photodynamic therapy, vision was stable at 20/200 with a reduction in lesion size on B-scan ultrasonography and no leakage on fluorescein angiography. With 10 months of follow-up there was no recurrence of leakage. CONCLUSION: Retinal capillary angioma may be present in association with familial exudative vitreoretinopathy, and photodynamic therapy may provide a good alternative treatment to decrease exudation.

Adult↗
PubMed2004

High-frequency ultrasound of anterior segment retinoblastoma.

PURPOSE: To evaluate anterior segment retinoblastoma with high-frequency ultrasound. DESIGN: Interventional case report. METHODS: An 11-year-old boy with a total retinal detachment and multiple white anterior chamber nodules was examined with high-frequency ultrasound before enucleation of the globe. RESULTS: Multiple solid and cystic nodular tumors were found in the anterior chamber angle. With high-frequency ultrasound, tumor was discovered posterior to the iris, over the ciliary processes, and on the lens capsule. No calcifications were noted. Other findings included angle closure related to iris neovascularization and uveal thickening. CONCLUSION: High-frequency ultrasound can be used to evaluate retinoblastoma extension into the anterior segment. These images may be used for comparison in future cases of retinoblastoma with anterior chamber invasion.

Anterior Eye Segment↗
PubMed2004

Visual recovery after radiation therapy for bilateral subfoveal acute myelogenous leukemia (AML).

PURPOSE: Present a case of bilateral foveal acute myelogenous leukemic tumors that responded to radiation therapy. DESIGN: Case report. METHODS: A patient was diagnosed with bilateral subfoveal infiltration of known systemic acute myelogenous leukemia. He received a standard induction chemotherapy, followed by consolidation therapy for his systemic leukemia. However, despite a complete marrow response, the intraocular tumors did not regress. Therefore, he was given low dose (1950-cGy) ocular external beam radiation therapy. RESULTS: One course of systemic cytarabine chemotherapy failed to control the subfoveal tumors, leaving the patient at risk for permanent vision loss. In contrast, external beam radiation therapy improved his vision from 20/60 in his right eye to 20/20 and from 20/70 in his left eye to 20/25. CONCLUSION: Although systemic chemotherapy can be used to treat intraocular metastasis, external beam radiation may provide more prompt resolution of vision-threatening tumors.

Adult↗
PubMed2005

Effect on ocular survival of adding early intensive focal treatments to a two-drug chemotherapy regimen in patients with retinoblastoma.

PURPOSE: To evaluate vincristine and carboplatin with intensive focal treatments in the management of intraocular retinoblastoma. DESIGN: Noncomparative, retrospective interventional case series. METHODS SETTING: Institutional. PATIENT POPULATION: Sixteen patients (11 bilateral, 5 unilateral) with intraocular retinoblastoma. Interventional procedures: Patients were treated with eight courses of vincristine and carboplatin. Intensive focal treatments were administered after two courses of chemotherapy. MAIN OUTCOME MEASURES: Avoidance of external beam radiotherapy (EBRT) and eye survival. RESULTS: Twenty eyes (74.1%) were classified as Reese-Ellsworth Group V. All eyes responded to chemotherapy. With a median follow-up of 23 months (range 10 to 33 months) and a median of 5.5 focal treatments per eye (range 0 to 19 treatments), ocular survival was 81%. Eight eyes (30%) in five patients received EBRT. CONCLUSIONS: Vincristine and carboplatin combined with intensive focal treatments is an effective regimen for patients with intraocular retinoblastoma. This treatment regimen has outcomes comparable to those of more toxic regimens and merits further evaluation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Visual loss as a first sign of adult-type chronic myeloid leukemia in a child.

PURPOSE: To report the unusual case of retinal leukemic infiltration in a child with adult-type chronic myelocytic leukemia. DESIGN: Interventional case report. METHODS: Complete ophthalmologic examination, including visual acuity measurement and funduscopy. The diagnosis was established by blood cell counts and confirmed by a positive Philadelphia-chromosome translocation (t [9,22]). Treatment consisted of hydroxyurea and stem-cell transplantation. RESULTS: After therapy, complete regression of the retinal lesion was observed with full recovery of visual acuity. CONCLUSION: This case underlines the importance of interdisciplinary cooperation between ophthalmologists and pediatric oncologists in the diagnosis and treatment of this disease.

Blindness↗