Radiation Of Optic Neuropathy Caused By Basic And Clinical Research

PartⅠEstablishment of rat model for radiation-induced optic neuropathy[Objective] Radiation-induced optic neuropathy (RION) is one of the devastating late complications of radiotherapy to the optic nerve or optic chiasm resulting in acute, painless and irreversible visual loss. Till now, the pathogenesis of RION has not yet been fully understood. Neurotrophic factors and angiogenesis inhibitor bevacizumab preliminarily show the potential to treat RION. Therefore, to lay a solid foundation for research on the pathogenesis and treatment of RION, we attempt to establish a rat model of RION by delivering a single radiation dose (30 Gy) to the optic chiasm.[Methods and Materials] Of all 34 Wistar rats,4 rats were un-irradiated as the control group, while the rest were irradiated and then randomized to the 2-month group, the 4-month group and the 6-month group according to the different feeding period after irradiation. Firstly, when the respective feeding periods of all groups expired, manganese-enhanced magnetic resonance imaging (MEMRI) scan were performed with the neuronal tracer MnCl2 injected into the vitreous of the eye 24 h prior to imaging. According to the different extents of the vision pathways’enhancement on MEMRI, a scoring system was defined. Secondly, the rats were killed humanely for histological studies with hematoxylin & eosin (HE)stain and Luxol Fast Blue (LFB) stain. Relative optical density value in the LFB stain and number of glial cells in the HE stain were also analyzed. Some specimens were selected for electron microscopy analysis.[Results] 4 rats died during feeding period after irradiation and 6 rats died from anesthesia before MEMRI scan. In the control group, the 2-month group, the 4-month group, and the 6-month group, the number of rats that received MEMRI scan were 4,5,4 and 11, respectively. There was a negative association between the scores of MEMRI and the intervals from irradiation to MEMRI scan, p=0.000. If the score of MEMRI was lower than 5, then it was defined as RION. According to this criterion, the ratio of RION in the four groups were 0/3,1/5,2/4 and 11/11, respectively. The chi-square test for inter-groups comparision showed x2=15.443, p=0.001.In addition, the number of specimens that received histological study were 3,7,4 and 7, respectively. In contrast with the specimens of un-irradiated rats, the specimens of 6 months after irradiation showed homogeneous pathological features in the HE and LFB stains-demyelinization, glial cells infiltration, capillary hyperplasia and interstitial f ibrinoid necrosis. There was an inverse correlation between the relative optical density value in the LFB stain and the interval between irradiation and pathological examination, p=0.000. Besides, the number of glial cells in the HE stain in the four groups were 194±65, 234±19,124±11 and 345±98, respectively. At the same time, the number of glial cells were positively associated with the feeding periods after irradiation, p=0.005. When compared findings of MEMRI scan with that of histological examination, we found that there was loss of signals of optic nerve and chiasm on MEMRI imaging in one of 5 rats in the 2-month group, while no significant histological difference was found between this rat and the others.[Conclusions] With a single dose of radiation (30 Gy) to the optic chiasm, a rat model of RION was successfully established which was comfirmed by the homogeneous pathological changes 6 months after irradiation. Radiation-induced optic neuropathy can be non-invasively detected by MEMRI scan, and also be semi-quantitative analysed according to the enhancement extent of the vision pathways on MEMRI. Moreover, RION can be early diagnosed by MEMRI scan which is capable to show physiological change in advance of pathological change.PartⅡThe dose-volume analysis of radiation-induced optic neuropathy in sinonasal and nasal cavity carcinoma treated with intensity modulated radiotherapy[Objective] To evaluate the incidence of radiation-induced optic neuropathy (RION) in sinonasal and nasal cavity carcinoma treated with intensity modulated radiotherapy (IMRT), three-dimensional dose-volume distributions for optic nerve and optic chiasm were calculated and analyzed.[Methods and Materials] From April,2004 to Nov,2009, a total of 93 patients with a diagnosis of sinonasal and nasal cavity carcinomas were treated in our department, among them,59 patients were treated with IMRT and were followed for greater than 12 months, and all of the 59 patients’ Dose-Volume Histogram (DVH) was available. To evaluate dose-volume effect of optic nerve and chiasm, patients were divided into 3 groups:the new-diagnosed group (49 patients), the re-irradiation group (4 patients), and the hypo-fraction group (6 patients). A Pinnacle treatment planning system was used for the treatment planning and dose-volume distribution analysis.[Results] With a median follow-up of 27.3 months (range,12-68), the 3-year local control, freedom from distant metastasis, disease-free survival and overall survival rate were 79.1%,77.9%,67.2%, and75.5%, respectively. One patient in the new-diagnosed group developed RION, the Dmax of the optic nerve and the chiasm was 69.28Gy and 66.54Gy, in 30 fractions; One patient in the re-irradiation group developed the right side vision loss 8 months after the secondary irradiation (he had received an initial 56Gy irradiation, with a 15-year interval, and then received a maximum dose of 65.86Gy to the right optic nerve in 30 fractions); no patient in the hypo-fraction group developed RION.[Conclusions] IMRT can provide proven outcomes for patients of sinonasal and nasal cavity carcinoma, the acceptable low incidence of RION was observed. The risk factors of RION such as the maximum dose, per-fraction dose, and re-irradiation should be considered in the treatment planning.