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.