Cornea Service, Glaucoma Service and Boston Keratoprosthesis Laboratory, Massachusetts Eye and Ear and Schepens Eye Research Institute, Harvard Medical School, Boston, MA.
Cornea. 2019 Dec;38(12):1589-1594. doi: 10.1097/ICO.0000000000002106.
To review clinical aspects and cellular and molecular steps in the development of long-term glaucoma after corneal surgery or acute trauma-especially the pivotal role of tumor necrosis factor alpha (TNF-α), the rapidity of the secondary damage to the retinal ganglion cells, and the clinical promise of early antiinflammatory intervention.
A series of laboratory studies on post-injury and post-surgery glaucoma have been compared to clinical outcome studies on the subject, focusing particularly on the vulnerability of the retinal ganglion cells. Alkali burn to the cornea of mice and rabbits served as the main experimental model. TNF-α titer, ganglion cell apoptosis, and depletion of optic nerve axons have been examined. Anti-TNF-α antibodies or corticosteroids have been used to protect the retinal ganglion cells. Intraocular pressure (IOP) postburn was recorded by manometric methods.
In animals with alkali burn to the cornea, damage to the retina can occur within 24 to 72 hours. This is not because of a direct pH change posteriorly-the alkali is effectively buffered at the iris-lens level. Rather, TNF-α (and other inflammatory cytokines), generated anteriorly, rapidly diffuses posteriorly to cause apoptosis of the ganglion cells. During this time, the IOP remains much lower than the reported values required to cause ganglion cell damage. The TNF-α antibody infliximab or corticosteroids, if administered promptly, are markedly protective of the ganglion cells.
A rapidly initiated, inflammatory (TNF-α mediated), IOP-independent pathway to glaucoma, resulting from acute anterior segment trauma or surgery, has been identified in laboratory studies. Prompt prophylactic treatment with antiinflammatory agents has been shown to be markedly neuroprotective of retinal ganglion cells, presumably capable of reducing the risk of late glaucoma.
回顾角膜手术后或急性创伤后长期青光眼的临床方面以及细胞和分子步骤 - 特别强调肿瘤坏死因子 α（TNF-α）的关键作用、对视网膜神经节细胞的继发性损伤的速度，以及早期抗炎干预的临床前景。
将一系列关于创伤后和手术后青光眼的实验室研究与该主题的临床研究结果进行了比较，特别关注视网膜神经节细胞的脆弱性。用角膜碱烧伤的小鼠和兔子作为主要实验模型。检查了 TNF-α 滴度、神经节细胞凋亡和视神经轴突耗竭。使用抗 TNF-α 抗体或皮质类固醇来保护视网膜神经节细胞。通过眼压计方法记录烧伤后眼内压（IOP）。
在角膜碱烧伤的动物中，视网膜损伤可在 24 至 72 小时内发生。这不是因为后部的直接 pH 值变化 - 碱在虹膜 - 晶状体水平被有效地缓冲。相反，TNF-α（和其他炎症细胞因子）在前部产生，迅速向后扩散，导致神经节细胞凋亡。在此期间，IOP 仍远低于报道的引起神经节细胞损伤所需的值。及时给予 TNF-α 抗体 infliximab 或皮质类固醇对神经节细胞具有显著的保护作用。
在实验室研究中已经确定了一种由急性前节创伤或手术引起的快速启动的炎症（TNF-α介导）、与 IOP 无关的青光眼途径。及时预防性使用抗炎药物已被证明对视网膜神经节细胞具有明显的神经保护作用，可能降低晚期青光眼的风险。
