Clinical manifestations and treatment of retinoblastoma in Korea.

BACKGROUND/AIMS: To analyse the clinical manifestations and results of treatment for patients with retinoblastoma in Korea. METHODS: The medical records of 70 children (92 eyes) diagnosed as having retinoblastoma and treated between 2000 and 2006 were retrospectively analysed. Data on gender, age at diagnosis, laterality, presenting sign, classification of tumour, treatment modality and prognosis were collected. RESULTS: The most common presenting sign was leucocoria (80%). 31.4% developed bilateral retinoblastoma. Using the International Classification of Retinoblastoma, 7.5% were group A, 23.8% were group B, 6.3% were group C, 38.8% were group D, and 23.8% were group E. 26.1% of eyes were treated with chemoreduction and/or focal therapy, namely, they achieved globe preservation, and all other eyes were enucleated. The globe preservation was achieved in 100% of group A, 77.8% of group B, 66.7% of group C, and 26.7% of group D. CONCLUSIONS: In Korea, most children with retinoblastoma showed an advanced stage of tumour at the time of diagnosis and although they were treated with an updated therapeutic approach according to the newly introduced classification, the rate of globe preservation did not reach that of developed countries. Increased surveillance should be performed.

Tandem high-dose chemotherapy and autologous stem cell rescue in children with bilateral advanced retinoblastoma.

Although external-beam radiation therapy (EBRT) has been an effective treatment modality in patients with bilateral advanced retinoblastoma, it significantly increases the risk of second malignancies and facial deformities. This study aimed to evaluate the efficacy of tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) for treatment, instead of EBRT, in children with bilateral advanced retinoblastoma. Fourteen patients with bilateral retinoblastoma received chemotherapy, and local therapy was provided whenever possible. When at least one functional eye could not be saved by chemoreduction and local therapy, tandem HDCT/ASCR was provided to avoid EBRT. As a result, nine patients received tandem HDCT/ASCR. The toxicities were tolerable and there was no TRM. All nine patients who received tandem HDCT/ASCR had at least one functional eye without EBRT, and in two patients, both eyes were saved. No second malignancy has developed to date. HDCT/ASCR might be an effective treatment for bilateral advanced retinoblastoma, especially in cases in which at least one functional eye could not be preserved with chemoreduction and local therapy alone, and where EBRT was unavoidable. Long-term follow-up and further studies are needed to evaluate the efficacy and toxicity of HDCT/ASCR as an alternative treatment to EBRT.

Types of macular hole closure and their clinical implications.

AIMS: To evaluate the clinical significance of macular hole closure types assessed by optical coherence tomography (OCT). METHODS: This study involved 34 eyes of 32 patients who had undergone anatomically successful idiopathic macular hole surgery. The closed macular holes were categorised into two patterns based on OCT; type 1 closure (closed without foveal neurosensory retinal defect) and type 2 closure (closed with foveal neurosensory retinal defect). Association between visual prognosis, type of hole closure, and possible prognostic factors were analysed. RESULTS: 19 eyes (61.3%) were classified into the type 1 closure and 12 eyes (38.7%) into the type 2 closure. The extent of postoperative visual improvement of type 1 closure group was larger than that of type 2 closure group (p=0.002). The preoperative macular hole size of type 2 closure group was significantly larger than that of type 1 closure group (p=0.006). The duration of symptoms was positively correlated with the preoperative macular hole size (p=0.01). Recurrence of macular hole occurred only in the type 2 closure group. CONCLUSION: The type of macular hole closure, which was influenced by the preoperative hole diameter, was associated with postoperative visual prognosis. Early detection and intervention in macular hole should be emphasised.

Sensitivity of CD95-induced apoptosis in different proliferative status of human retinal pigment epithelial cells.

It is known that CD95 (APO-1/Fas) is expressed on the cell surface, and apoptotic cell death can be induced by the CD95 ligation in the cultured, proliferating human retinal pigment epithelial (RPE) cells. However, little is known about CD95 on the non-proliferating RPE cells. In this study, human RPE cells were cultured up to 4 weeks after they reached the confluence, to simulate the non-proliferating RPE cells in situ. There was no significant difference in CD95 expression on the cell surface between the predominantly proliferating, preconfluent cells and predominantly non-proliferating, postconfluent cells in flow cytometric assays. However, unlike proliferating cells, no cellular death occurred in the predominantly non-proliferating cells after the treatment of agonistic anti-CD95 antibody with cycloheximide, pretreated with interferon-gamma. Our results suggest that the CD95/CD95L system probably plays a physiologic role in vivo to remove the abnormal, proliferating RPE cells, and factors other than the surface expression of CD95 may determine the sensitivity to the CD95 signals.

Macular hole surgery in conjunction with endolaser photocoagulation.

PURPOSE: To determine whether endolaser photocoagulation to the retinal pigment epithelium at the base of a macular hole increases the anatomic success rate of surgery. METHODS: In a prospective consecutive clinical trial, eight eyes of seven patients with idiopathic macular hole underwent vitrectomy with posterior cortical vitreous removal and peeling of visible epiretinal membrane when present. A single shot of argon endolaser photocoagulation was applied to the retinal pigment epithelium at the center of the macular hole with a duration of 0.05 to 0.2 seconds and an intensity of 50 to 200 mW. After fluid-gas exchange was performed with 14% perfluoropropane gas, patients maintained face-down positioning for 2 weeks. RESULTS: One eye with stage 2 macular hole, six eyes with stage 3 macular hole, and one eye with stage 4 macular hole were included. All eight eyes had a closed macular hole (100% anatomic success rate) at final examination 6 to 12 months after surgery. Best-corrected visual acuity improved 3 or more lines on the Early Treatment Diabetic Retinopathy Study visual acuity chart in all eyes. Four (50%) of the eight eyes had a final visual acuity of 20/40 or better. CONCLUSIONS: Endolaser photocoagulation may be a useful adjunct to macular hole surgery but requires further investigation and long-term evaluation.

CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion.

Despite the fact that integrin-mediated lymphocyte adhesion is a crucial event for an appropriate immune response, little is known about the mechanisms that control the adhesion and deadhesion processes generated by the engagement of CD99 between various types of immune cells. Here we report that the CD99 gene encodes two distinct proteins with opposite functions in the LFA-1/intercellular adhesion molecule 1 (ICAM-1)-mediated cell adhesion process. The two forms of the CD99 protein are produced by alternative splicing of the CD99 gene transcript. The major form induced homotypic adhesion of the human B lymphoblastoid cell line IM-9, whereas the minor, truncated form inhibited the adhesion process. Activation of the major form of CD99 with anti-CD99 monoclonal antibodies induced rapid aggregation of IM-9 cells, which was blocked by the addition of mAbs to LFA-1 or intracellular adhesion molecule 1. Overexpression of the minor truncated form of CD99 markedly down-regulated the expression of LFA-1. The two forms of CD99 are differentially expressed in most human cells tested and are highly conserved in monkey. Taken together, these observations suggest that the two forms of CD99 function in vivo in both positive and negative regulation of LFA-1-mediated adhesion of lymphocytes during an immune response.

Preretinal neovascularization induced by experimental retinal vein occlusion in albino rats.

Retinal ischemia and neovascularization have been demonstrated in several animal models. To determine 1) whether the retinal or preretinal neovascularization can be induced in albino rats by retinal vein occlusion and 2) the type and rate of occurrence on neovascularization, we occluded retinal veins in albino rats by photodynamic thrombosis. After anesthesia, each of 36 rats received an injection of rose bengal photosensitive dye, and their veins underwent argon green laser treatment. Half or all the major retinal veins were occluded in 12 eyes and in 24 eyes, respectively. Ten control rats underwent the same procedures but the laser beam was directed between major retinal vessels. In 46 control eyes, rose bengal dye was seen to have perfused without laser treatment. Retinal detachment developed in most vein occluded eyes within one day of venous occlusion, which was confirmed by fluorescein angiography. On follow-up at two weeks, only four of 24 eyes (16.7%) had undergone occlusion of all retinal veins showed new preretinal vessels on the optic disc. In these four eyes, severe disturbance of both retinal arterial and venous blood flow was observed, but no other eyes showed such severe combined disturbance. These data suggest that preretinal neovascularization in albino rats can be induced by this minimally traumatic method and that venous occlusion is severe enough to compromise arterial blood flow for a certain threshold period, thus inducing the development of preretinal neovascularization.

Thymocytes positively select thymocytes in human system.

We previously demonstrated the expression of MHC class II molecules in a significant percentage of human fetal and postnatal thymocytes. These results, at that time, raised the question as to whether the MHC class II molecules on immature thymocytes could actively be involved in the selection of immature T cells. We have developed a human reaggregate culture system to address this issue. Surprisingly, despite the fact that thymic epithelial cells (TECs) have been shown to be a major selecting cell type of positive selection, we were clearly able to see the involvement of MHC class II+ thymocytes during selection process through T-T interaction. In addition, maturation to single positive (SP) cells occurred only in the presence of MHC class II molecules and immature thymocytes were found to be arrested at the double positive (DP) stage of differentiation by blocking of TCR recognition of MHC class II molecules. All these results strongly suggest that human MHC class II+ thymocytes actively participate in the selection of the TCR repertoire, for which TCR recognition of peptide/MHC class II may be an initial determining step.

A tectonic keratoprosthesis using expanded polytetrafluoroethylene as a supporting skirt in humans.

A tectonic keratoplasty was performed with a keratoprosthesis using expanded polytetrafluoroethylene as a supporting skirt, on the left eye of a 23-year-old woman who needed an emergency corneal transplantation due to corneal perforation. The keratoprosthesis implanted, consisted of a supporting skirt which was made of expanded polytetrafluoroethylene (PTFE), and an optic portion which was made of polymethylmethacrylate (PMMA). The optic portion and the supporting skirt were attached by cyanoacrylate tissue adhesive (Histoacryl). Two months post-operatively, the keratoprosthesis was extruded, leaving an opacified, vascularized cornea. A penetrating keratoplasty was performed 1 month later. The excised cornea was composed of granulation tissue. To our knowledge, this is the first case of tectonic keratoprosthesis using expanded PTFE as a supporting skirt in humans.