葡萄膜黑色素瘤经巩膜表面敷贴放射治疗的预后及其影响因素

巩膜表面敷贴放射治疗是治疗葡萄膜黑色素瘤的一种近距离放射疗法,肿瘤局部控制率、转移率以及患者生存率与其他疗法相比并无差异,但能保留眼球并维持部分视力,对正常组织及全身损伤较小,安全且疗效可靠.治疗预后受肿瘤大小、位置、退行速度、生长方式、敷贴剂量率、放射性核素的种类、敷贴器放置的精准度、敷贴器的形状以及患者年龄等多种因素影响.     

葡萄膜恶性黑色素瘤的敷贴放疗

敷贴放疗在许多国家已成为治疗葡萄膜恶性黑色素瘤最常采用的方法，本文通过对葡萄膜恶性黑色素瘤的敷贴放疗的历史、现状、适应证、疗效、并发症、与其它疗法的比较等介绍，显示了敷贴放疗用于治疗葡萄膜恶性黑色素瘤的优越性。     

葡萄膜恶性黑色素瘤的敷贴放疗

敷贴放疗在许多国家已成为治疗葡萄膜恶性黑色素瘤最常采用的方法，本文通过对葡萄膜恶性黑色素瘤的敷贴放疗的历史，现状，适应证，疗效，并发症，与其它疗法的比较等介绍，显示了敷贴放疗用于治疗葡萄膜恶性黑色素瘤的优越性。     

葡萄膜黑色素瘤的放射敷贴治疗现状

葡萄膜黑色素瘤是成人最常见的原发眼内恶性肿瘤[1] ,可发生于虹膜、睫状体及脉络膜 ,多数葡萄膜黑色素瘤位于后部葡萄膜[2 ] 。放射敷贴疗法是一种近距离放射治疗 ,是多年来治疗葡萄膜黑色素瘤最常用的方法之一[3] 。早在 1930年 ,Ｍｏｏｒｅ[4 ] 曾用镭针治疗脉络膜黑色素瘤。 196 6年Ｓｔａｌｌａｒｄ[5] 首先报道使用60 Ｃｏ放射敷贴器治疗脉络膜黑色素瘤。自 2 0世纪 70年代至今 ,12 5Ｉ、10 6Ｒｕ、192 Ｉｒ及10 3Ｐａ相继用于放射敷贴法治疗葡萄膜黑色素瘤。一、用于放射敷贴治疗的放射性元素的物理特点用于放射敷贴治疗的放射性元素…     

葡萄膜黑色素瘤动物模型的建立

葡萄膜黑色素瘤是成年人最常见的原发性眼内恶性肿瘤,在过去的数十年里,研究葡萄膜黑色素瘤所面对的主要挑战是建立合适的动物模型.最常见的葡萄膜黑色素瘤动物模型可分为动物的自发性肿瘤、诱发肿瘤和移植性肿瘤.开始应用人葡萄膜黑色素瘤细胞系和肿瘤组织碎片建立模型是原发的和转移的实验性动物模型的一大进步.葡萄膜黑色素瘤动物模型常被用于原发和转移葡萄膜黑色素瘤的预后因素及治疗手段等方面的研究.尽管动物模型与人类的疾病有一定差异,但它们确实为研究人葡萄膜黑色素瘤的发生、发展、转移预后及治疗手段等方面提供了有力的工具.本文对近年来葡萄膜黑色素瘤动物模型研究做一综述.     

国产125I巩膜敷贴器治疗兔眼脉络膜黑色素瘤的有效性及安全性研究

背景 脉络膜黑色素瘤(CM)是成人眼内常见的原发性恶性肿瘤,巩膜表面敷贴放射治疗(EPRT)是一种近距离放射疗法,是多年来治疗CM最常用的方法之一.但该治疗方法的研究与应用目前在国内报道较少,大多数的CM患者需行眼球摘除术. 目的 通过观察兔CM模型眼、正常兔眼经敷贴放射后的反应以及兔全身免疫状态,评价国产125I巩膜敷贴器的有效性及安全性.方法 新西兰大白兔40只,按随机数字表法分成5个组,每组8只兔8只眼(均取右眼).其中放射治疗组1及模型对照组用于评价国产125I巩膜敷贴器的有效性;放射治疗组2、伪放射对照组、正常对照组用于评价国产125I巩膜敷贴器的生物安全性.有效性研究:利用B16F10鼠皮肤黑色素瘤细胞株植入兔眼制作动物模型,造模3周后放射治疗组1模型兔眼放置国产125I巩膜敷贴器进行放射治疗,肿瘤局部照射总剂量为100 Gy,模型对照组不进行治疗.每日间接检眼镜检查,每周行眼底照相、B型超声、彩色超声多普勒检查.安全性研究:放射治疗组2正常兔眼放置巩膜敷贴器,伪放射对照组正常兔眼植入不带放射粒子的敷贴器外壳,正常对照组不作任何干预.放射治疗组2、伪放射对照组于放置敷贴器前及敷贴器取出后3、7、15、30 d抽取外周血,用流式细胞术检测外周血CD4+、CD8+T细胞数量.于放射治疗组1、模型对照组肿瘤种植后6周,放射治疗组2、伪放射对照组、正常对照组观察30 d后耳缘静脉空气栓塞法处死实验兔,对实验眼进行常规组织病理学检查. 结果 放射治疗组1、模型对照组间放置敷贴器前肿瘤的平均高度差异无统计学意义(P=0.550).放置敷贴器1周后,放射治疗组1肿瘤高度明显小于模型对照组,差异有统计学意义(P=0.001);放射治疗组1放置敷贴器2周后肿瘤高度较敷贴前明显缩小,差异有统计学意义(P=0.007).常规组织病理学检查发现,与模型对照组比较,放射治疗组1虽然仍有肿瘤细胞残存,但肿瘤内部血管明显减少且管径较细,肿瘤细胞排列紊乱,部分细胞空泡样变性,色素外露,大量纤维结缔组织增生.安全性研究中,放射治疗组2、伪放射对照组在各时间点CD4+、CD8+、CD4+/CD8+T细胞流式细胞术结果比较,差异均无统计学意义(F分组=0.770、8.110、2.230;P=0.380、0.060、0.140;F时间 =0.770、3.220、4.230;P=0.550、0.170、0.004).放射治疗组2、伪放射对照组表现为角膜、结膜上皮下、巩膜表面慢性炎性细胞浸润,未见巩膜坏死、机化等表现. 结论 国产125I巩膜敷贴器对兔眼CM的疗效确切,对眼部其他组织以及兔全身免疫状态的影响较小.     

葡萄膜黑色素瘤的质子束疗法

葡萄膜黑色素瘤治疗中应用二种主要放疗技术。放射性敷贴器可缝于肿瘤区巩膜上,亦可应用粒子放射,如质子和氦离子。后一方法的优点是假定为肿瘤和正常组织间有较好的剂量分布,则质子或氦离子所释放的剂量可更精确地限局于肿瘤区,可将所有或某些对放射敏感的眼内组织摒除在放射区之外。另外,它还有均匀性放射量射至整个肿瘤。这些由带电粒子所提供的优良剂量分布在眼科放疗范围内可有以下临床优点:     

葡萄膜黑色素瘤患者巩膜外敷贴放射治疗反应模式及治疗效果

目的:观察并分析葡萄膜黑色素瘤（UM）患者巩膜外敷贴放射治疗（PRT）的不同临床反应模式以及治疗失败后行二期眼球摘除手术的危险因素。方法:单中心回顾性研究。2011年3月至2017年9月于北京同仁医院眼科检查确诊并接受 125I巩膜外PRT的465例UM患者纳入研究。其中,男性217例,女性248例;年龄（...     

葡萄膜黑色素瘤局部切除术及其预后因素的研究进展

眼球摘除术作为葡萄膜黑色素瘤传统的治疗方法已受到挑战。放射治疗和肿瘤局部切除术等保留眼球的治疗方法在不少国家已成为主要的治疗手段。本文就葡萄膜黑色素瘤局部切除术的发展史、适应证、手术技术、并发症和预后等进行综述     

葡萄膜黑色素瘤临床病理特征与预后的相关因素分析

目的 观察葡萄膜黑色素瘤的临床及病理特征与肿瘤转移和肿瘤所致死亡的相关预后因素。方法 53例行眼球摘除手术并经组织病理学检查证实为葡萄膜黑色素瘤患者的临床资料纳入研究。记录患者年龄、性别、患眼眼别、视力、眼压、虹膜新生血管、肿瘤形态、肿瘤大小、继发视网膜脱离等临床特征,以及肿瘤细胞类型、是否侵犯睫状体、巩膜导管、视盘、...     

Regression of Posterior Uveal Melanomas Following Cobalt-60 Plaque Radiotherapy

A method has been devised for evaluating the rate and extent of regression of the first 100 consecutive patients with a posterior uveal melanoma that we had managed by Cobalt-60 plaque radiotherapy at Wills Eye Hospital. It was found that the "average" posterior uveal melanoma in the series did not regress rapidly to a flat, depigmented scar but shrank slowly and persisted as a residual mass approximately 50% of the thickness of the original tumor at 54 months following Cobalt-60 plaque radiotherapy. We also found that the rate and extent of regression of the tumors in patients who subsequently developed metastatic melanoma were not appreciably different than the rate and extent of regression of the tumors in patients who remained well systemically. These observations indicate that the rate and extent of regression of posterior uveal melanomas following Cobalt-60 plaque radiotherapy are poor indicators of the prognosis of the affected patients for subsequent development of clinical metastatic disease.     

Choroidal melanoma: current therapeutic approaches

The management of posterior uveal melanoma has evolved tremendously over the past decades and more recently there has been a trend toward more focal conservative treatment. Transpupillary thermotherapy (TTT) with infrared diode laser (810nm) is the newest modality used as primary treatment or as a complement to radiotherapy or surgical resection in selected cases of choroidal melanoma. Plaque radiotherapy or charged-particle irradiation is particularly recommended for medium- or small-sized uveal melanoma not suitable to TTT or resection. Special custom-designed plaque radiotherapy (iodine-125) can be used for the iris and ciliary body, or in juxtapaillary choroidal melanoma. The tumor control rate after plaque or charged-particle radiotherapy appears to be similar but charged-particle irradiation may produce worse anterior-segment complications than plaque radiotherapy. Stereotactic radiation therapy for choroidal melanoma may be effective in controlling tumor growth, but the number of patients treated with this approach is too small to draw solid conclusions. Local tumor resection using trans-scleral resection is mainly suitable for selected iris, ciliary body, or anterior choroidal melanoma, particularly with smaller basal dimensions and greater thickness. Endoresection may preserve central vision or temporal field when radiotherapy would be expected to cause optic neuropathy. Longer follow-up is necessary to establish the efficacy of tumor control. Combined therapies (radiotherapy plus TTT or tumor resection plus TTT) appear to be more effective in decreasing the incidence of intraocular tumor recurrence. Enucleation is still performed for large uveal melanoma when there is no hope of regaining useful vision. Based on the published ophthalmology literature, it seems that enucleation carries the same survival prognosis as each of the conservative treatment modalities.     

Ocular motility disturbances after episcleral plaque brachytherapy for uveal melanoma.

OBJECTIVE: To evaluate contributions of various factors in the development of strabismus after iodine-125 brachytherapy for uveal melanoma. METHODS: Twenty consecutive patients who underwent episcleral plaque brachytherapy for uveal melanoma underwent a full orthoptic examination before and after the surgery. Iodine-125 seeds at 5-mCi strengths were used with a mean total dose of 10.400 cGy toward the tumor apex. RESULTS: Average follow-up time was 25.4 months (range, 14 to 40). At 12 months all tumors showed regression, 9 patients had visual acuity of 20/200 or better, and 4 patients had ambulatory vision. After tumor treatment, 8 patients were orthophoric, 9 patients developed exotropia, 1 patient became hypertropic, 2 patients developed exotropia and hypertropia. Of 2 patients who developed significant diplopia, 1 received 10 U botulinum-toxin A injection (Botox, Allergan, Irvine, CA) for exotropia, and the other was managed with superior rectus advancement and superior oblique tenectomy for surgery-induced iatrogenic Brown's syndrome and slipped superior rectus muscle. CONCLUSION: Extensive mechanical injury, possible ionizing radiation of the plaques, and low visual acuity may cause strabismus after episcleral plaque brachytherapy. Diplopia and cosmesis could be improved with Botox injection or strabismus surgery.     

Choroidal neovascularization induced by transcleral microdiathermy for localization of a juxtapapillary choroidal melanoma.

Transcleral transillumination is a useful tool for the localization of juxtapapillary uveal tract tumors that do not cast a shadow with conventional transpupil-lary transillumination. The main choice of treatment for juxtapapillary uveal tract melanoma consists of either episcleral plaque brachytherapy or proton beam radiotherapy. In both instances, an external surgical approach is required that involves localization of the tumor and marking of the overlying sclera. Transcleral microdiathermy often creates corresponding areas of chorioretinal atrophy. This article describes the technique of transcleral transillumination coupled with microdiathermy to mark the sclera in a patient in whom a choroidal neovascular membrane developed adjacent to a microdiathermy-induced area ofchorioretinal atrophy after the described surgical technique. To avoid the postoperative development of a choroidal neovascular membrane, transcleral transillumination can be used without the application of microdiathermy.     

New treatment modalities for uveal melanoma

The management of uveal melanoma has evolved tremendously for the past century, and more recently there is a trend toward more focal conservative treatment. Enucleation is still performed for large uveal melanoma when there is no hope for useful vision with conservative treatment. Plaque radiotherapy is particularly recommended for medium- or small-sized uveal melanoma. Special custom-designed plaque radiotherapy can be used for iris, ciliary body, or juxtapapillary choroidal melanoma. Charged-particle irradiation constitutes an alternative treatment modality for posterior uveal melanoma. However, charged-particle therapy is limited by the availability of appropriate therapeutic facilities. Local tumor resection using lamellar sclerouvectomy is mainly suitable for selected iris, ciliary body, or anterior choroidal tumors with smaller basal dimension and greater thickness. Ablative laser photocoagulation is indicated for very selected cases of small posterior choroidal uveal melanoma. Combined plaque radiotherapy with indirect ophthalmoscope laser therapy appears to be a more effective local tumor treatment plan than plaque radiotherapy alone. Transpupillary thermotherapy is the newest modality used as primary treatment or as complementary method to brachytherapy for treatment of selected choroidal melanomas. Hyperthermia with infrared irradiation below photocoagulation level produces tumor necrosis with few ocular complications. Based on the published ophthalmic literature, it seems that enucleation carries the same survival prognosis as each of the conservative treatment modalities.     

Lipid exudation following plaque radiotherapy for posterior uveal melanoma

PURPOSE: To investigate factors associated with lipid exudation after plaque radiotherapy for uveal melanoma. DESIGN: Retrospective interventional case series. METHODS: Records of 139 consecutive uveal melanoma patients treated with I-125 plaque radiotherapy were reviewed. Lipid exudation was the major outcome measured. RESULTS: Lipid exudation was detected in 19 patients (13.7%). Mean time from plaque therapy to lipid exudation was 10 months (range, 3-23 months). Lipid exudation was associated with younger patient age (P = .0002), increased low-density lipoprotein (P = .004), decreased high-density lipoprotein (P = .026), increased tumor thickness (P = .024), and exudative retinal detachment (P = .016). Patients with lipid exudation had worse visual outcome (P < .0001) and increased neovascular glaucoma (P = .01). CONCLUSIONS: Lipid exudation after plaque radiotherapy for uveal melanoma is associated with poor ocular outcome. Factors associated with this lipid exudation are distinct from those associated with radiation retinopathy, and they may suggest interventions to combat this complication.     

Enucleation after plaque radiotherapy for posterior uveal melanoma. Histopathologic findings

A review of 1019 patients with posterior uveal melanomas, who were treated with episcleral plaque radiotherapy between April 1976 and December 1987, showed that 59 (6%) of these patients have thus far required enucleation of the affected eye. The most common clinical reasons for enucleation were tumor regrowth (51%) and neovascular glaucoma (31%). These irradiated melanomas were of mixed cell type in 40 cases (68%), spindle in 10 cases (17%), totally necrotic in 7 cases (12%), and epithelioid in 2 cases (3%). Some degree of tumor necrosis was seen in all cases. Overall, the median number of mitoses per 40 high-power fields in these irradiated tumors was 0. Most (64%) of the tumors had no identifiable mitosis in 40 high-power fields. A three-way simultaneous comparison of the following groups was made: irradiated eyes enucleated for tumor regrowth, irradiated eyes enucleated for neovascular glaucoma, and a matched group of nonirradiated posterior uveal melanomas. This comparison showed that the largest tumor dimension was significantly greater in the irradiated eyes enucleated for tumor regrowth than in the other two groups. Mitotic activity was significantly higher in the irradiated tumor regrowth and nonirradiated groups than in the irradiated neovascular group. There was no significant difference among the three groups in an analysis of height. The results suggested that mitotic activity may exist after plaque radiotherapy, especially when there is clinical evidence of tumor regrowth.     

Regression of posterior uveal malignant melanomas after cobalt plaque radiotherapy

We reviewed the records of 17 patients with posterior uveal malignant melanoma who had been followed for at least 3 months prior to cobalt plaque radiotherapy and whose tumor had been documented to enlarge in thickness during that interval. We evaluated the relationship between the rates of pretreatment tumor enlargement and post-treatment tumor shrinkage using linear regression analysis. We found that the rate of postirradiation tumor shrinkage correlated strongly with the rate of preirradiation tumor enlargement regardless of whether the pretreatment rate of growth was slow, intermediate or rapid. We speculate that the more rapidly regressing tumors were more mitotically active than their more slowly regressing counterparts. If true, the survival rate of patients whose posterior uveal malignant melanomas regress rapidly following radiation therapy may prove to be worse than that of patients whose tumors regress slowly.     

Periocular triamcinolone for prevention of macular edema after iodine 125 plaque radiotherapy of uveal melanoma

OBJECTIVE: To investigate the potential benefit of periocular depot triamcinolone in the prevention of macular edema after iodine 125 plaque radiotherapy for uveal melanoma. METHODS: This comparative, nonrandomized, interventional study included 87 patients with uveal melanoma who underwent plaque radiotherapy. The triamcinolone group included 55 consecutive patients who were treated with 40 mg of periocular triamcinolone at the time of plaque application and 4 months and 8 months later. The comparison group comprised 32 consecutive patients treated with plaque radiotherapy without triamcinolone. Patients were evaluated at 4 months, 8 months, 12 months, 18 months, and 24 months after plaque application with clinical examination, fundus photography, and optical coherence tomography (OCT). The associations of clinical variables with the development of OCT-evident macular edema (the main outcome measure) were investigated using Cox proportional hazards analysis. RESULTS: By multivariate analysis, eyes treated with periocular triamcinolone had a significant reduction in the risk of radiation-induced macular edema (P = 0.002; hazard estimate = 0.49; 95% confidence interval, 0.17- 0.80). Adverse effects associated with periocular triamcinolone treatment included elevation of intraocular pressure (7% of cases) and blepharoptosis (5% of cases). CONCLUSIONS: Periocular triamcinolone treatment significantly lowered the risk of macular edema after plaque radiotherapy for uveal melanoma in this series but did not significantly alter the rate of vision loss at 24 months of follow-up.     

Bilateral primary choroidal melanoma treated with bilateral plaque radiotherapy: a report of three cases

PURPOSE: To report three cases of bilateral primary choroidal melanoma treated with bilateral plaque radiotherapy. METHODS: Retrospective, single-center case series. RESULTS: Case 1: In 1981, a 50-year-old man was diagnosed with a 5-mm-thick choroidal melanoma in the right eye (OD) and treated with plaque radiotherapy. In 1994, a 6.8-mm-thick choroidal melanoma in the left eye (OS) was treated with plaque radiotherapy. Final visual acuity was light perception OD and 20/20 OS at 24 years follow-up. Case 2: In 1983, a 53-year-old woman was diagnosed with a 3.5-mm-thick choroidal melanoma OS and treated with plaque radiotherapy. In 2001, an enlarging 2.5-mm-thick choroidal melanoma OD was treated with plaque radiotherapy. Final visual acuity was 20/30 OD and 20/20 OS at 22 years follow-up. Case 3: In 2001, a 92-year-old man was diagnosed with a 7.9-mm-thick choroidal melanoma OD treated with plaque radiotherapy. In 2003, an enlarging 2.8-mm-thick juxtapapillary choroidal melanoma was treated with plaque radiotherapy. Final visual acuity was 20/70 OD and 20/60 OS at 2.5 years follow-up. No patient showed ocular melanocytosis. Stable tumor regression was achieved in all six eyes. Metastatic disease did not develop in any case over 16 years of follow-up. CONCLUSIONS: Monitoring of both eyes of patients with uveal melanoma is important for the remote possibility of melanoma in the second eye. In these three patients, plaque radiotherapy allowed for preservation of the globes and some vision.