巩膜敷贴放射治疗后葡萄膜黑色素瘤的退行及其与预后的关系

葡萄膜黑色素瘤是成年人眼内最常见的恶性肿瘤.巩膜敷贴放射治疗是葡萄膜黑色素瘤临床保留眼球的主要治疗方式,能有效控制肿瘤生长,但放疗后肿瘤退行反应异质性明显.有研究提出巩膜敷贴放疗后肿瘤退行速度可作为巩膜敷贴放射治疗预后因素,退行速度越快预后越差.一些学者研究发现,肿瘤初始高度、3号染色体单体化、GEP分型与巩膜敷贴放疗...     

视网膜母细胞瘤的巩膜敷贴放射治疗疗效观察

目的 评价巩膜敷贴放射疗法对于视网膜母细胞瘤(Rb)治疗的有效性.方法 对用巩膜敷贴放射治疗的Rb患儿16例(18眼)的疗效进行观察分析.结果 16例(18眼)Rb患儿经巩膜敷贴放射治疗后,在3～24个月的随访中,肿瘤成功得到控制15眼(83%);发生并发症及转移而摘除眼球3眼.未发现明显全身不良反应.并发症有放射性白内障4眼(22%),继发性青光眼4眼(22%),玻璃体出血3眼(16.7%).所有患眼均未发生巩膜坏死.1例患儿肿瘤复发并眼外转移.结论 巩膜敷贴放射疗法是治疗Rb的一个有效方法.     

Episcleral plaque radiotherapy for uveal melanoma

The use of radioactive Iodine, Ruthenium, Iridium and Cobalt plaques of varying dimensions to treat choroidal and ciliochoroidal melanomas is discussed and placed in perspective with other treatment modalities. The regression pattern following plaque treatment appears to be more rapid for tumours that are more poorly differentiated. The visual results following plaque brachytherapy compare very favourably with those following local resection and external beam radiation. Ocular complications are significantly greater for tumours whose initial thickness exceeds 8 mm. The survival rater after plaque treatment is compared with that for patients who have had primary enucleation for equivalent-sized tumours.     

Cataract surgery following cobalt-60 plaque radiotherapy for posterior uveal malignant melanoma

We reviewed the records of thirteen patients with posterior uveal malignant melanoma who had developed a mature radiation cataract following cobalt-60 plaque radiotherapy. Cataract extraction had been performed in seven of these patients as of the survey date of this investigation. We attempted to determine if cataract extraction increased the risk of metastatic melanoma, improved or worsened visual function, or resulted in any consistent intraoperative or postoperative complications that did not occur if the cataract was retained. Our analysis showed that removing the cataract did not appear to increase the risk of death from metastatic melanoma, but it also indicated that cataract extraction did not seem to improve the visual function of the irradiated eye. On the basis of our experience to date, we offer suggested guidelines for the management of patients who develop a mature cataract following cobalt-60 plaque radiotherapy of a posterior uveal malignant melanoma.     

葡萄膜恶性黑色素瘤治疗新进展

葡萄膜恶性黑色素瘤(uveal melanoma,UM)是成人最常见的原发性眼内恶性肿瘤。虽然目前治疗手段多种多样,眼球摘除术仍是本病的传统治疗,但手术摘除眼球并不能完全控制肿瘤的远处转移。对于伴全身转移的患者,据30a来的统计,生存率仍很低。近年来许多研究致力于靶向治疗、免疫治疗、放射治疗,并取得了可喜的效果,本文对相关研究进行综述。     

国产敷贴器治疗葡萄膜转移癌的安全性和有效性

目的 探讨国产敷贴器治疗葡萄膜转移癌的安全性及有效性。设计 回顾性病例系列。研究对象 2015年10月至2018年3月北京同仁医院由病史、临床和影像学诊断为葡萄膜转移癌,经国产敷贴器进行巩膜外敷贴放射治疗的患者16例（16眼）。方法 记录患者治疗前后视力、眼压,彩色超声多普勒（CDI）测量瘤体大小（最大基底直径、最大高度）,间接眼底镜、CDI及OCT下观察视网膜下液情况。采用SPSS22.0对结果进行分析。主要指标 视力、眼压、肿瘤大小,视网膜下液吸收情况及有无并发症发生。结果 16例患者手术中无活动性出血,无眼肌、涡静脉、视神经等损伤,术后无感染、巩膜融解等并发症发生。术后2例失访。14例患者术前与末次随访比较,视力无明显变化（P=0.69）（术前0.24±0.29,末次随访0.21±0.26）、眼压无明显变化（P=0.39）（术前13.3±5.8 mmHg,末次随访16.0±12.9 mmHg）,术后瘤体萎缩（最大基底直径：术前14.9±2.6 mm,末次随访9.9±3.9 mm,P<0.001;最大高度：术前6.3±1.9 mm,末次随访2.4±1.3 mm,P<0.001）。所有得到随访数据的14例患者在末次随访时间接眼底镜、CDI及OCT下未观察到视网膜下液的存在。结论 国产敷贴器治疗葡萄膜转移癌安全、有效。（眼科, 2018, 27： 388-391）     

Personalized treatment of uveal melanoma

Personalized treatment of uveal melanoma involves the tailoring of all aspects of care to the condition, needs, wishes, and fears of the patient, taking account of the individual''s circumstances. When selecting between radiotherapy, surgical resection, and phototherapy, or when deciding how best to combine these different therapeutic modalities, it is necessary to understand the patients utilities, with respect to tumour control, visual conservation, and preservation of the eye, so as to prioritize outcomes accordingly. For example, such considerations would influence the width of the safety margins when administering radiotherapy, according to whether the patient considers it more important to conserve vision or to guarantee tumour control. With ‘suspicious naevi'', the choice between observation, immediate treatment, and biopsy is complicated by the lack of adequate survival data on which to base rational decisions, making it necessary for both patient and doctor to accept uncertainty. Personalized care should involve close relatives, as appropriate. It must also adapt to changes in the patient''s needs over time. Such personalized care demands the ability to respond to such needs and the sensitivity to identify these requirements in the first place. Personalized treatment enhances not only the patient''s satisfaction but also the ‘job satisfaction'' of all members of the multidisciplinary team, improving quality of care.     

RNA干扰技术在葡萄膜黑色素瘤治疗中的展望

葡萄膜黑色素瘤是成年人中最多见的一种恶性肿瘤。该肿瘤恶性程度高，预后较差，易行血流转移，主要通过眼球摘除术及相应的放疗、化疗治疗，但效果均不理想和确切。RNA干扰技术的出现已成为生命科学研究和临床治疗的又一次革命。利用RNA干扰技术，体外合成葡萄膜黑色素瘤中的相关的小片段核苷酸（19核苷酸），通过基因工程方法构建质粒，转染人葡萄膜黑色素瘤细胞，对葡萄膜黑色素瘤基因表达产生抑制作用，将会成为治疗葡萄膜黑色素瘤的一条新途径。     

Patients presenting with stage IV uveal melanoma: Lessons learned

Challenges persist in identifying patients with stage IV uveal melanoma. While clinical, histopathologic, and genetic features of the primary tumor have been shown to provide prognostic value for assessing metastatic risk, biopsy-related genetic analyses are expensive and not universally available. Therefore, this review will focus on clinical characteristics. Initial staging and follow-up screening protocols have evolved for patients with uveal melanoma. The Collaborative Ocular Melanoma Study (COMS) required a physical examination, chest X-ray, and hematologic survey (primarily liver function tests). Though these studies were found to have a high specificity, COMS investigators typically found late-stage metastases. More recently, protocols have concentrated on liver imaging (abdominal ultrasound, computed tomography, and magnetic resonance imaging). Though hepatic radiographic imaging has been found more likely to reveal earlier metastatic uveal melanoma, by definition it cannot detect most extrahepatic and multiorgan metastases. An international multicenter registry study recently focused on patients who were diagnosed with stage IV uveal melanoma simultaneously with their primary intraocular melanoma. Therein, utilizing center-specific diagnostic methods, stage IV was found to occur in about 2% of patients. However, subgroup analysis found that a disproportionate number of multi-organ metastases were discovered when whole-body positron emission tomography/computed tomography was used for staging. Herein, we review the literature on patients who present with stage IV uveal melanoma, how they were detected, and their outcomes.     

Current management of uveal melanoma: A review

Uveal melanoma is the most frequent primary intraocular cancer in adulthood and is mostly localised to the choroid. It can be treated using radiation therapy, laser therapy, local resection and enucleation, with the best results achieved by combining these procedures. However, up to half of patients develop metastatic disease. There are no efficacious treatment methods for patients in advanced stage or with metastasis. In recent years, several novel treatment modalities aimed at improving tumour control and reducing adverse events have emerged. This review summarises current clinical treatment methods and new therapeutic perspectives for uveal melanoma.     

Paediatric uveal melanoma

Uveal melanoma is extremely rare in the paediatric population and can be associated with various pre-existing conditions. We report the case of a 9-year-old girl with no predisposing factor who presented with choroidal melanoma. A review of the literature is presented and various clinical, histopathological and prognostic features of paediatric uveal melanoma are discussed.     

Comparison of primary and secondary enucleation for uveal melanoma

We investigated operative course and post-operative findings of patients undergoing primary enucleation for uveal melanoma versus those requiring secondary enucleation after brachytherapy. A retrospective chart review was performed with IRB approval on patients receiving treatment for uveal melanoma. Patients with enucleation as initial treatment and patients enucleated after plaque brachytherapy were analyzed for demographic data, operative course, and post-enucleation outcome. Further cause analysis for secondary enucleations was investigated. No significant difference was seen in age, laterality, or gender between the primarily enucleated (n = 54) and secondarily enucleated (n = 34) groups. Greater difficulty with surgery was noted in 28/32 (87.5%) of secondary enucleations compared to 1/54 (1.8%) of primary enucleations (p < 0.0001). Operative time was >2 hours in 3/51 (6%) of primary enucleations (vs. 8 of 32, 25%, p = 0.02). Average implant size was similar in the 2 groups (20.6 mm), however 2/34 (6%) of secondary enucleations required dermis fat grafting. Post-enucleation anophthalmic ptosis occurred after 8/49 (16%) of primary cases (vs. 13/30, 43%, p = 0.02) and prosthetic enophthalmos after none (0%) of primary cases (vs. 5/30, 17%, p = 0.006). Class 2 gene expression profile was found in 6/8 (60%) of eyes enucleated for treatment failure. Secondary enucleation performed after plaque brachytherapy was technically more difficult, and had more anophthalmic socket and eyelid complications compared to primary enucleation for uveal melanoma. Primary enucleation may avoid additional surgery and morbidity in a subset of patients with contraindications to plaque brachytherapy.     

Current trends in the treatment of ocular melanoma by radiotherapy

The Collaborative Ocular Melanoma Study (COMS) has recently confirmed once and for all that it is safe to attempt to preserve an eye with a posterior uveal melanoma by demonstrating no survival advantage of enucleation over plaque radiotherapy. While COMS has been under way, we have set out in London to define the selection criteria for conservative therapy versus enucleation for the various categories of melanoma in terms of size, location within the eye, and presence or absence of retinal detachment. The evolution of this approach has culminated in an overall ocular survival rate of 94% in 597 patients following radiation therapy combined with a mean loss of visual acuity of only 2.4 Snellen lines in the eyes preserved.     

Recurrence of posterior uveal melanoma after 60Co episcleral plaque therapy

The authors analyzed the clinical and follow-up data on 277 selected patients with primary choroidal or ciliochoroidal melanoma who were treated with 60Co plaque radiotherapy between 1976 and 1982. Local recurrence of the irradiated melanoma developed in 39 (14%) patients during the follow-up interval. The 5-year tumor recurrence rate (Kaplan-Meier) was estimated to be 12%. Multivariate prognostic factor analysis (Cox proportional hazards modeling) identified the largest linear tumor dimension and proximity of the posterior margin of the tumor to the optic nerve head as predictors of recurrence. The 5-year survival rate of patients whose tumors recurred (58%) was significantly (log-rank test P = 0.0023) worse than that of patients whose tumor remained clinically controlled (82%).     

Developments in the management of uveal melanoma

Uveal melanomas threaten visual loss, enucleation, and death from metastatic disease. Most patients present because of symptoms, but failures of detection and diagnosis still occur commonly. Treatments aimed at avoiding enucleation include: plaque, proton beam or stereotactic radiotherapy; trans-scleral or trans-retinal local resection; and transpupillary thermotherapy. Increasingly, different modalities are being used in combination. The ocular outcomes are related to tumour size, location, spread and cell type. Metastatic disease occurs in many patients and is related to factors such as tumour dimensions, ciliary body involvement, cell type, extravascular matrix patterns and cytogenetics. Abnormalities related to chromosomes 3, 6 and 8 are strongly related to tumour behaviour, for the first time enabling survival probability to be estimated with a high degree of reliability in an individual patient. This enables high-risk individuals to be targeted for screening while providing reassurance to those with a minimal chance of developing metastatic disease. Such targeting would allow selection of patients for adjuvant systemic therapy, should a suitable treatment become available, and would also facilitate the evaluation of such treatment by increasing the statistical power of any randomized prospective study. The high mortality in patients with monosomy 3 melanoma suggests that in these patients ocular treatment is only palliative. Cytogenetic studies suggest that some melanomas may never develop any metastatic potential and if these impressions are confirmed by further studies, then in these patients the main priority of treatment would be to conserve vision.     

Inflammation in uveal melanoma

Leukocytic infiltration is a common feature of human cancers, including those that develop in immunoprivileged sites, such as the eye. The infiltration of myeloid and T cells into tumours is part of the host response against cancer. In uveal melanoma, high densities of immune cells seem to be involved in tumour progression, as they are associated with the loss of one chromosome 3. The nature of this tumour microenvironment might offer therapeutic opportunities.     

Evolving systemic targeted therapy strategies in uveal melanoma and implications for ophthalmic management: a review

Uveal melanoma (UM) is the most common primary ocular tumour in adults. Despite good local control of the primary tumour with current methods, survival after the development of metastasis has remained poor over the last 30 years. After cutaneous melanoma, UM is the most common type of melanoma, and an ongoing debate exists regarding whether these conditions should be considered separate entities, particularly in the context of targeted therapy, where many of the initial trials for patients with metatatic cutaneous melanoma excluded metastatic UM. This paper will review the recent and ongoing investigations designed to validate systemic targeted therapy and immunotherapy in patients with metastatic UM and suggests ways in which these developments may affect management of UM by ophthalmologists in the near future.