目的：识别新生血管性年龄相关性黄斑变性（neovascular age-related macular degeneration,NVAMD）患者接受抗血管内皮生长因子（vascular endothelial growth factor,VEGF）药物治疗后出现的黄斑萎缩事件，并评估其治疗前的眼部解剖结构变化。方法：回顾 2014 全年期间由采用抗 VEGF 药物治疗的所有 NVAMD 患者，这些患者的随访时间均超过 12 个月，并评估了从首次治疗（通常在 2014 年前）至 2018 年 6 月最后一次随访期间的所有谱域光学相干断层扫描（spectral domain-optical coherence tomography, SD-OCT）图像。结果：在既定的研究流程中，共识别出 278 例 NVAMD 患者的 342 眼，其中 47 眼发生了黄斑萎缩。从治疗开始到黄斑萎缩出现的中位时间为 29.6 个月（四分位距：17.7-43.4）。在发生萎缩的区域中，发现了三种黄斑结构改变（部分眼睛存在不止一种改变）：在 25 眼中观察到血管化色素上皮脱离（pigment epithelial detachment,PED）的塌陷和脉络膜新生血管（choroidal neovascularization，CNV）的消退；在 15 眼中观察到视网膜下高反射物质和(或)视网膜下纤维化的形成；在 13 眼中观察到黄斑萎缩与大玻璃膜疣及色素改变相关联，呈现出通常称为地图状萎缩的典型模式。结论：这些数据表明，在某些情况下，CNV 可能补偿脉络膜的缺血状态，而 CNV 的消退则可能使 RPE 细胞和光感受器暴露于缺血性损伤和萎缩的风险之中。

Background/Aims: To identify incident macular atrophy and evaluate antecedent anatomic alterations in eyes with neovascular age-related macular degeneration (NVAMD) that were treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Methods: All patients treated with anti-VEGF agents for NVAMD by one of the authors during the 2014 calendar year who had follow up ≥ 12 months had evaluation of all SD-OCT scans from first treatment (usually prior to 2014) to last follow up through June 2018.  Results: The ascertainment procedure identified 342 eyes of 278 patients with NVAMD among which 47 developed macular atrophy. The median time from treatment initiation to development of macular atrophy was 29.6 (interquartile range, 17.7 - 43.4) months. Three macular alterations were identified in areas that developed atrophy (some eyes had more than one); collapse of a vascularized pigment epithelial detachment (PED) and regression of choroidal neovascularization (CNV) in 25 eyes, development of subretinal hyper-reflective material and/or subretinal fibrosis in 15 eyes, or atrophy occurring in association with large drusen and pigmentary changes resulting in an arc of atrophy in a pattern typically referred to as geographic atrophy in 13 eyes. Conclusions: These data suggest that in some instances CNV may compensate for choroidal ischemia and the loss of CNV may expose retinal pigmented epithelial cells and photoreceptors to ischemic damage and atrophy.

目的：研究基质金属蛋白酶-2（Matrix metalloproteinase-2, MMP-2）、基质金属蛋白酶-9（Matrix metalloproteinase-9, MMP-9）和血管内皮生长因子（Vascular endothelial growth factor, VEGF）在视网膜母细胞瘤（Retinoblastoma, RB）中的表达及其与 RB 分化程度和视神经浸润的关系，探讨它们在 RB 浸润、转移过程中的作用和临床意义。

方法：采用免疫组化方法检测 40 例 RB 中 MMP-2、MMP-9 和 VEGF 的表达。

结果：40 例 RB 中 MMP-2、MMP-9 和 VEGF 的阳性表达率分别为 52.5%、57.5% 和 72.5%。未分化型 RB 中 MMP-2、MMP-9 和 VEGF 的阳性表达均高于分化型（P < 0.05）；有视神经浸润的 RB 中 MMP-2、MMP-9 和 VEGF 的阳性水平均高于无视神经浸润的 RB（P < 0.05）。RB 中 MMP-2、MMP-9 和 VEGF 的表达呈正相关关系（P < 0.05）。

结论：RB 中 MMP-2、MMP-9 和 VEGF 高表达与 RB 的浸润和转移相关，且 MMP-2、MMP-9 表达与 VEGF 表达存在相关性。联合检测 MMP-2、MMP-9 和 VEGF 的表达可作为反映 RB 浸润、转移潜能的生物学指标，有助于筛选转移高危病例及评价患者预后。

Purpose: To study the expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in retinoblastoma (RB) and its relationship with the differentiation and optic nerve infiltration of RB. And to investigate the role of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and VEGF in the infiltration and metastasis of RB and their clinical significance.

Methods: Immunohistochemical technique was used to detect the protein expression of MMP-2, MMP-9 and VEGF in 40 RB cases.

Results: The MMP-2, MMP-9 protein and VEGF protein expression were detected as positive in 52.5%, 57.5% and 72.5% of 40 RB cases respectively. The expression of MMP-2, MMP-9 and VEGF was significantly higher in the undifferentiated pattern than in the rosetted pattern (p < 0.05); and the expression of MMP-2, MMP-9 and VEGF was significantly higher in tumors with optic nerve invasion than in those without optic nerve invasion (p < 0.05). In RB, the expression of MMP-2, MMP-9 had a positive correlation with the expression of VEGF.

Conclusions: In RB, high expression of MMP-2, MMP-9 and VEGF is related to the invasion and metastasis of RB. The expression of MMP-2, MMP-9 is positively correlated with the expression of VEGF. The expression of MMP-2, MMP-9 and VEGF may act as a biological marker for the invasion and metastasis of RB. The method may help screen and identify the cases with high risk for metastasis and to predict the prognosis of patients.