Objective: This study correlated the patterns of ocular B- and A-scans of intraocular retinoblastoma (RB) with corresponding histopathology sections. It aimed to establish a more objective basis for determining intraocular retinoblastoma by ultrasonography (UTZ) and to determine the degree of malignancy and viability of the tumor cells. Methods: New cases of retinoblastoma seen at the University of the Philippines-Philippine General Hospital (UP-PGH) from January 1994 to December 2003 were reviewed. Included were patients who underwent enucleation and whose eyeballs were processed at the UP Institute of Ophthalmology. Those with good quality ocular ultrasonographs (UTZ) and clear matching histopathologic sections were finally selected. Findings were correlated and analyzed.Results: Retinoblastoma (RB) showed multiplicity of lesions on UTZ corresponding to multiple lesions on histopathology. The following characteristic patterns were seen: Very malignant RB or pseudorosettes: fine, grainy densities on B-scan with short to medium broad spikes on A-scan ("V-W" pattern). Moderate differentiation with moderate necrosis and early calcific plaques: fine, dense grainy opacities on B-scan with multiple thin, high spikes admixed with tall, broad spikes of calcium deposits on A-scan. Well-differentiated RB with compact viable cells and no necrosis: large, white densities on B-scan with an initial high spike and high internal reflectivity, sometimes "plateauing," on A-scan with no calcific deposits. Complete tumor necrosis with calcific plaques: echolucent space with dense, white, plaque-like opacities on B-scan; flat or low spikes mixed with tall, broad spikes corresponding to calcium plaques on A-scan. Normal vitreous, serous subretinal fluid, or recent hemorrhage: echolucent area on B-scan with flat or low spikes on A-scan. Conclusion: The three most frequent findings in intraocular retinoblastoma were calcific plaques with liquefaction necrosis, multiplicity of lesions, and pseudorosettes. Ocular ultrasound of retinoblastoma showed good histopathologic correlation.
Human ; RETINOBLASTOMA ; ULTRASONOGRAPHY ; RETINAL NEOPLASMS ; RETINAL DISEASES ; EYE DISEASES ; PATHOLOGY

Eye Enucleation ; Humans ; Infant ; Retinal Neoplasms ; surgery ; Retinoblastoma ; surgery ; Vitrectomy

Child ; Consensus ; Humans ; Infant ; Retinal Neoplasms/diagnosis* ; Retinoblastoma/diagnosis*

Retinoblastoma (RB) is the most common intraocular malignant tumor in infants and young children. The key causative factors in the progression of RB remain unclear. Therefore, identifying genes closely associated with RB progression may provide important clues for disease diagnosis and gene therapy. However, tumor tissues have strong cellular heterogeneity. There may be significant differences in cell function and gene expression among cells in different pathological states. In this study, we downloaded single-cell transcriptome sequencing data of RB tumors and adjacent tissues from the GEO public database. Subsequently, we analyzed RB tumor transcriptional profiles with different disease duration at the single-cell level and identified cell groups and gene sets potentially associated with RB progression. The results showed that the tumor tissue and the adjacent tissues had overall consistency in the single-cell transcriptional map, but there were obvious differences in the distribution proportions of G1 phase cells, G2 phase cells, and microglia cells of cone precursors in RB tumor and the adjacent tissues. Furthermore, the role of three cell populations in the progression of RB tumors was emphatically analyzed. We found that in the early stage of RB tumors, cone precursor cells proliferated abnormally in G1 phase. With the progression of RB tumors, the proportion of cone precursor cells in G2 phase increased significantly. Meanwhile, the results of differential analysis of microglial populations during RB progression showed that the key genes mainly involved in immune response include RPL23, B2M, and HLA superfamily genes. This study provides new perspectives and data resources for the research of RB pathogenesis and progress.
Child ; Infant ; Humans ; Child, Preschool ; Retinoblastoma/pathology* ; Transcriptome ; Retinal Neoplasms/pathology*

OBJECTIVE: To report a case of radiation retinopathy, a common complication in the treatment of nasopharyngeal carcinoma. METHOD:This is a case report. RESULTS:A 59-year-old Chinese man with a history of external beam irradiation for nasopharyngeal carcinoma presented with mild blurring of vision of the left eye.Examination revealed bilateral scattered cotton-wool spots, intraretinal hemorrhages, and microaneurysms.The left eye had peripapillary cotton-wool spots and hemorrhages, disc edema, and semimacular star.Funduscopic findings were similar to those of diabetic retinopathy except for the abundance of cotton-wool spots and the presence of macular star. CONCLUSION:Radiation retinopathy usually develops 6 months to 3 years after exposure.In this patient, it occurred 2 years after radiotherapy.Neovascularization at the disc developed 15 months after initial presentation, which required treatment with panretinal photocoagulation, resulting in regression of the new vessels.As severe late ocular complications frequently occur after radiation therapy, periodic ophthalmologic examinations should be considered.
Human ; Male ; Middle Aged ; NASOPHARYNGEAL NEOPLASMS ; RETINAL NEOVASCULARIZATION ; DIABETIC ANGIOPATHIES ; DIABETIC RETINOPATHY ; ;

PURPOSE: To report a case of bilateral branch retinal vein occlusion development after taking long-term tamoxifen adjuvant therapy. CASE SUMMARY: A 72-year-old female breast cancer patient with a 10-year history of tamoxifen intake presented with decreased visual acuity that began 5 years prior. The patient had no other past history. The best corrected visual acuity (BCVA) was 0.3 in the right eye and 0.04 in the left eye. There was no specific finding of anterior segment on slit lamp examination. On fundus examination, sheathed branch retinal veins were observed in the inferotemporal area of the right eye and superotemporal and inferotemporal areas of the left eye. Microangiopathies were observed around the occluded branch retinal veins in both eyes and macular edema was present in the left eye. Laser photocoagulation was performed at the non-perfusion area in both eyes and an intravitreal injection of bevacizumab and 3 intravitreal injections of triamcinolone were administered into the left eye. The BCVA did not change after 3 years and remained relatively stable. CONCLUSIONS: If a patient presents with decreased visual acuity after taking tamoxifen, fundus examination and fluorescein angiogram should be performed due to the possibility of branch retinal vein occlusion.
Aged ; Bevacizumab ; Breast Neoplasms ; Female ; Fluorescein ; Humans ; Intravitreal Injections ; Light Coagulation ; Macular Edema ; Retinal Vein Occlusion* ; Retinal Vein* ; Retinaldehyde* ; Slit Lamp ; Tamoxifen* ; Triamcinolone ; Visual Acuity

The risk of radiotherapy-related secondary cancers in children with constitutional retinoblastoma 1 (RB1) mutations has led to reduced use of external beam radiotherapy (EBRT) for RB. Presently, tumor reduction with chemotherapy with or without focal surgery (chemosurgery) is most commonly undertaken; EBRT is avoided as much as possible and is considered only as the last treatment option prior to enucleation. Nevertheless, approximately 80% of patients are diagnosed at a locally advanced stage, and only 20-25% of early stage RB patients can be cured with a chemosurgery strategy. As a whole, chemotherapy fails in more than two-thirds of eyes with advanced stage disease, requiring EBRT or enucleation. Radiotherapy is still considered necessary for patients with large tumor(s) who are not candidates for chemosurgery but who have visual potential. When radiation therapy is indicated, the lowest possible radiation dose combined with systemic or local chemotherapy and focal surgery may yield the best clinical outcomes in terms of local control and treatment-related toxicity. Proton beam therapy is one EBRT method that can be used for treatment of RB and reduces the radiation dose delivered to the adjacent orbital bone while maintaining an adequate dose to the tumor. To maximize the therapeutic success of treatment of advanced RB, the possibility of integrating radiotherapy at early stages of treatment may need to be discussed by a multidisciplinary team, rather than considering EBRT as only a last treatment option.
Child ; Child, Preschool ; Eye Neoplasms/genetics ; Genes, Retinoblastoma/genetics ; Humans ; Radiotherapy Dosage ; Retinal Neoplasms/*radiotherapy ; Retinoblastoma/genetics/*radiotherapy

A 56-year-old female patient presented with decreased visual acuity in her right eye lasting for one day. During the first visit, best corrected visual acuity (BCVA) was 20/80 and 20/20, in the right and left eye, respectively. Fundus examination of the right eye revealed an elevated mass in the superior area of the optic disc and exudative retinal detachment in the macula. Choroidal metastatic tumor secondary to non-small-cell lung cancer (NSCLC) was diagnosed after systemic work up. Photodynamic therapy (PDT) and the intravitreal bevacizumab injection for choroidal metastatic carcinoma were performed. After six months, the BCVA of the right eye was improved to 20/25. Complete regression of the tumor was noticed and serous detachment was resolved. There has been no recurrence for six months. We observed that combined treatment with PDT and intravitreal bevacizumab injection is effective in BCVA improvement and tumor regression, in a patient with choroidal metastasis of NSCLC.
Antibodies, Monoclonal, Humanized ; Choroid ; Eye ; Female ; Humans ; Lung ; Lung Neoplasms ; Neoplasm Metastasis ; Photochemotherapy ; Recurrence ; Retinal Detachment ; Triazenes ; Visual Acuity ; Bevacizumab

The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for metastasis and disease recurrence. Therefore, targeting CSCs has the potential to significantly improve outcomes for cancer patients. The OCT4 transcription factor gene is a master gene that plays a key role in the self-renewal and pluripotency of stem cells. In this study, we introduced an OCT4 reporting vector into 4T1 mouse breast cancer cells and sorted OCT4 high and OCT4 low cell populations. We then determined whether OCT4 expression is associated with maintenance and expansion of CSCs. We found that OCT4high 4T1 cells have an increased ability to form tumorsphere and a high expression of stem cell markers such as Sca-1, CD133, CD34, and ALDH1, when compared with OCT4low 4T1 cells. In addition, OCT4high 4T1 cells have greater tumorigenic potential in vivo. These findings suggest that OCT4 expression may be a useful target for stem cell-specific cancer therapy.
Animals ; Breast ; Breast Neoplasms ; Humans ; Isoenzymes ; Mice ; Neoplasm Metastasis ; Neoplastic Stem Cells ; Recurrence ; Retinal Dehydrogenase ; Stem Cells ; Transcription Factors

OBJECTIVEIdentification of Rb1 mutations permits accurate genetic counseling. Characterization of the causative mutation in a large low penetrance family is likely to provide important information for tumorigenesis of retinoblastoma(RB).

METHODSQuantitative fluorescent multiplex PCR QFM-PCR technique was used for mutation detection. Long fragment PCR, reverse transcriptase-PCR, subcloning, direct sequencing and Western blotting techniques were used for characterizing the mutation.

RESULTSA deletion covering exons 24 and 25 of Rb gene was found in a large family with 122 members in four generations. Of the 18 carries in the family, only 11 were delivered to either unilateral or bilateral RB. The family has much low-penetrance retinoblastoma, compared with the usual, high-penetrance RB (95%). An extent of 4 kb fragment deletion was detected in genomic deletion of the mutation. cDNA and sequence data showed a 174 bp shorter than the wild type message RNA resulting in an in-frame loss of 58 residues. Further analysis demonstrated the truncated protein expression of 6000 Da shorter than wild type RB1 protein.

CONCLUSIONQFM-PCR technique has enabled the investigators to identify a large deletion covering entire exons 24 and 25 of the Rb1 gene. It is the largest deletion ever found in low penetrance RB families. The characterizations of the mutation in genomic DNA, RNA and protein have provided new evidences which enhance credence to the idea that low penetrance retinoblastoma is caused by only partially functional disable of Rb1. The data will be useful in genetic counseling, particularly significant for the unaffected carriers in RB low penetrance families.

Exons ; Female ; Gene Deletion ; Gene Expression ; Humans ; Male ; Pedigree ; Penetrance ; Retinal Neoplasms ; genetics ; Retinoblastoma ; genetics ; Retinoblastoma Protein ; genetics