Retinoblastoma is lethal by metastasis if left untreated, so the primary goal of therapy is to preserve life, with ocular survival, visual preservation and quality of life as secondary aims. Historically, enucleation was the first successful therapeutic approach to decrease mortality, followed over 100 years ago by the first eye salvage attempts with radiotherapy. This led to the empiric delineation of a window for conservative management subject to a “state of metastatic grace” never to be violated.

Over the last two decades, conservative management of retinoblastoma witnessed an impressive acceleration of improvements, culminating in two major paradigm shifts in therapeutic strategy. Firstly, the introduction of systemic chemotherapy and focal treatments in the late 1990s enabled radiotherapy to be progressively abandoned. Around 10 years later, the advent of chemotherapy in situ, with the capitalization of new routes of targeted drug delivery, namely intra-arterial, intravitreal and now intracameral injections, allowed significant increase in eye preservation rate, definitive eradication of radiotherapy and reduction of systemic chemotherapy.

Here we intend to review the relevant knowledge susceptible to improve the conservative management of retinoblastoma in compliance with the “state of metastatic grace”, with particular attention to (i) reviewing how new imaging modalities impact the frontiers of conservative management, (ii) dissecting retinoblastoma genesis, growth patterns, and intraocular routes of tumor propagation, (iii) assessing major therapeutic changes and trends, (iv) proposing a classification of relapsing retinoblastoma, (v) examining treatable/preventable disease-related or treatment-induced complications, and (vi) appraising new therapeutic targets and concepts, as well as liquid biopsy potentiality.

如果不及时治疗，视网膜母细胞瘤会因转移而致死，因此治疗的主要目标是维持生命，以眼部存活，视觉保持和生活质量为次要目标。从历史上看，摘除术是降低死亡率的第一种成功的治疗方法，其后在100多年前进行了放射疗法的首次眼部挽救尝试。这导致了对经验主义保守管理窗口的经验性描绘，该窗口受制于永远都不能违背的“转移宽限状态”。

在过去的二十年中，视网膜母细胞瘤的保守治疗取得了令人印象深刻的加速改善，最终在治疗策略上发生了两次重大的模式转变。首先，在1990年代后期引入了全身化学疗法和局部治疗，使得放射治疗逐渐被放弃。大约10年后，随着靶向药物输送新途径的资本化（即动脉内，玻璃体内和现在的前房内注射）的到来，原位化学疗法的出现使眼保存率显着提高，彻底根除了放疗并减少了全身性化学疗法。

在这里，我们打算回顾与“转移性宽限状态”相符的易于改善视网膜母细胞瘤保守治疗的相关知识，并特别注意（i）审查新的成像方式如何影响保守治疗的前沿，（ii）剖析视网膜母细胞瘤的发生，生长方式和眼内肿瘤传播途径，（iii）评估主要的治疗变化和趋势，（iv）提出复发性视网膜母细胞瘤的分类，（v）检查可治疗/可预防的疾病相关或治疗引起的并发症，以及（vi）评估新的治疗目标和概念以及液体活检的潜力。