| Retinoblastoma is the most common primary malignant intraocular tumor in children, severely threatening their visual acuity,eyeball and life. Among all the treatments for retinoblastoma enucleation of eyeball is the most common and useful treatment. In order to elevate the quality of life of retinoblastoma patients, the conservative treatments were given more and more attention by oculists, along with the improvement of the diagnosis and treatments for retinoblastoma. In our coutry, it was mostly on the advanced stage,when diagnosis for retinoblastoma patient, and the rate of conservative treatment was very low, and the effect of conservative treatment was not comparatively well. In order to enhance the therapeutical effect,it is necessary for us to find the more effective and economic conservative treatments. Intraocular chemotherapy may be one of the most effective conservative treatments. Now my study includes: to analyze the characteristics of diagnosis and treatments, the condition of conservative treatments for retinoblastoma, and to further study the safety and validity of intraocular chemotherapy through animal experiments. Part I The Cinical Characteristics of Diagnosis and Treatments for RetinoblastomaObjective To analyze the clinical characteristerics of dianosis and treatments for retinoblastoma.Methods To retrospectively analyze the clinical document of 317 cases(362 eyes) of retinoblastoma in our hospital from 1996 to 2005.Result In our country, leucocoria is the most common symptom, 81.39%of all the symptoms in primary diagnosis. The average age of primary diagnosis is 30.18 months, the lasting time for the main complaint is 117.86 days,the thickness of the intraocular tumor is 10.71 mm. There is 1.89% of all the retinoblastoma patients who has family history, 0.37% for simple eye patients, 10.42% for both eyes patients. There is 8.22% of all the retinoblastoma patients who has more than one intraocular tumor, 3.20% for simple eye patients, 21.18% for both eyes patients. Retinoblastoma Staging:intracular stage(55.33%), glaucoma stage(10.00%), extraocular stage(32.67%), metastasis stage (1.00%) and spontaneous atrophy stage(1.33%). Treatments included tratinonal therapeutical methods and conservative treatments, 9.39% for the rate of abandoning treatments,12.50% for conservative treatment, 91.46% for eyeball removal.Conclusion In our country, it is more late for retinoblastoma patients to go to hospital, indicating the severity of patient's condition and more large for intraocular tumors and more proportion for the case number of extraocular stage ; The rate of conservative treatment is very low, and the rate of eyeball removal is very high, indicating the low level of technology for retinoblastoma treatment; And so early diagnosis and prompt treatment should be advocated, at the same time to study more cost-effective methods for retinoblastoma treatment. Part II The Clinical Analysis of Conservative Treatments for RetinoblastomaObjective To analyze and study the current situation and the correlated clinical facters for conservative treatment..Methods To retrospectively analyze the clinical document of 34 cases(35 eyes) of retinoblastoma who adopted conservative treatments in our hospital from 1996 to 2005. Conservative treatments included local therapy, chemoreduction therapy and alleviative treatment.Results The failure rate of conservative treatment was 62.5%. For the preliminary diagnosis age,the time of conservative treatment and the diameter of the tumor there was no statistical difference(P>0.05)between the two groups for success and failure. For the thickness of the tumor, there was great statistical difference(P<0.05). For the failure rate of conservative treatment, there was great statistical difference(P<0.05) between different location for intraocular tumors.Conclusion In our country, the failure rate of conservative treatment was very high, and the successful rate for conservative treatment is very low compared with developed nations; And there is a certain relationship between the volume, location of the tumors and the effect of the conservative treatments.Part III The Study on Safety for Intraocular ChemotherapyObjective To study the toxic effects of etoposide to the rabbit eye when injected into its vitreous body,evaluate its safety,to provide certain preparation for further clinical practice.Methods 24 healthy rabbits without any eye diseases were divided into 6 groups randomly, according to the intravitreal dose of etoposide : 1.5μg,15μg,150μg,375μg,750μg,1500μg. Besides there were normal groug (2 rabbits and 4 eyes)and control groug(4 rabbits and 8 eyes). The scotopic ERG responses were recorded, 1 d before the injection and 1 d,3 d,7 d,12 d after the injection. On the 12 d after the injection, kill the animals,all the eyes were examined by light microscopy and transmission electron microscopy, to observe the morphological changes of all the rabbit eyes.Results For the first 3 groups with its dose of 1.5μg,15μg,150μg(including normal groug and control groug), no evidence of toxicity was founded by scotopic ERG, light microscopy and transmission electron microscopy, before and after intravitreal injection of etoposide; but for the last 3 groups of 375μg,750μg,1500μg, the remarkable morphological changes of the rabbit eyes appeared in scotopic ERG, histopathology and ultrastructure, after the intravitreal injection of etoposide.Conclusion Etoposide is toxic to the rabbit eye, especially for its retinae, and the degree of the toxicity relying on its doses; it is more sensitive for posterior pole retinae to periphery retinae ; The safe dose of intravitreal etoposide is not less than 150μg, much higher than the effective, tumor-inhibitory concentration in vitro, indicating its high safety and validity, further suggesting its clinical feasibility.Part IV The Establishment of Animal Model for RetinoblastomaObjective To establish successful and stable animal model for retinoblastma, preparing for the further study.Methods 40 rabbits were devided into 10 groups according to the number of the retinoblastoma cells and immunity suppression factors: control group, 8 group, 7 group, 6 group, hormone group, subconjunctive group, CSA group, CTX group and CSA+CTX group. Besides there was a control group(2 rabbits and 4 eyes). Afer injection, observation for the tumor in rabbits'anterior chamber was done every day. The rabbits were killed on 30d for histopathology and immunohistochemistry. Analyze the rate of tumor emerging, the time of tumor emerging and lasting time of tumor, at the same time comparing statistically between each group.ResultsThe tumor could grow in some extent for 8 group, 7 group, hormone group, subconjunctive group, CSA group, CTX group and CSA+CTX group with 100% for the rate of tumor emerging, and there were great difference between latency period and lasting time of tumor for those groups. The tumor could not grow for control group and 6 group, with 0% for rate of tumor emerging. It can not lengthen the lasting time of tumor in anterior chamber by simply applying hormonal eye drops or subconjunctival injection of dexamethasone; But, it can lengthen the lasting time of tumor in anterior chamber by simply applying cyclosporin A eye drops or cyclophosphamide intravenous drip, and the effect will be better if combining the two methods .Conclusion The tumor can grow in some extent when the concentration of retinoblastoma cells injected into rabbits anterior chamber is more than 4×107个/ml; It will be a better animal model of retinoblastoma, which the tumor can exist for at least 30 days in the anterior chamber. The conditions includes: the concentration of retinoblastoma cells injected into rabbits anterior chamber is more than 4×107个/ml; simply applying cyclosporin A eye drops or cyclophosphamide intravenous drip, or combining the two methods.PartⅤThe Study on the Treatment Effects for Intraocular ChemotherapyObjective To study the effect of the intraocular chemotherapy for retinoblastma and the factors influencing the effect of the intraocular chemotherapy for retinoblastma.Methods 88 rabbits with Rb tumor in their anterior chamber were devided into 11 groups by chance by the size of the tumor in anterior chamber and the dose of intraocular chemotherapy(8 eyes for each group): control group,Ⅲ150 group,Ⅲ 75 group,Ⅲ37.5 group,Ⅲsubconjunctive group,Ⅲvein group,Ⅴ150 group,Ⅴ75 group,Ⅴ37.5 group,Ⅴsubconjunctive group andⅤvein group. Afer intraocular chemotherapy, the local eye and total body condition were observed every day. The rabbits were killed on 30d for histopathology and immunohistochemistry. To analyze the healing rate and the control rate, and then the two rates was analyzed statistically.Results It is 100% of the healing rate for intraocular chemotherapy group(Ⅲ150 group,Ⅲ75 group,Ⅲ37.5 group,Ⅴ150 group,Ⅴ75 group,Ⅴ37.5 group,) including different size of the tumor and different drug dose, but 0% of healing rate for subconjunctival injection group(Ⅲsubconjunctive group andⅤsubconjunctive group) and intravenous drip group(Ⅲvein group andⅤvein group). Meanwhile, there is different extent control of the tumor for subconjunctival injection group and intravenous dripgroup. For the intraocular chemotherapy group, it is shorter for the healing time when the tumor is smaller, and it is better for the effect of treatment when the drug dose is higher. There were great difference between groups with the same tumor height and different doses and groups with the same dose and different tumor heights.Conclusion It is the better treatment method for intraocular chemotherapy compared with subconjunctival injection and intravenous injection, which has higher healing rate; the effect of intraocular chemotherapy can be influenced by the size of the intraocular tumor and the dose injected into anterior chamber.
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