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Editors Selection IGR 15-4

Basic Science: Translaminar pressure gradient

Comment by Rand Allingham on:

57047 Optic neuropathy induced by experimentally reduced cerebrospinal fluid pressure in monkeys, Yang D; Fu J; Hou R et al., Investigative Ophthalmology and Visual Science, 2014; 55: 3067-3073

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Damage to retinal nerve fibers at the lamina cribrosa is pathognomonic for glaucoma. While it has been clear for over a century that IOP plays an important role in glaucomatous optic neuropathy (GON), numerous population-based studies have found that normal IOP is present in a high percentage of glaucoma cases. More recently, there has been a growing interest in how the translaminar pressure difference, produced by IOP and cerebrospinal fluid pressure (CSFp), may be related to GON. Several retrospective and prospective clinical studies support the role of reduced CSFp in POAG. Notably lacking have been chronic animal models to investigate this hypothesis. In the first of its kind, Yang and co-workers have studied the effect of chronically reduced CSFp in an experimental monkey model. A lumbar-peritoneal CSF shunt was placed in eight animals, was opened in four and remained closed in the control group. CSFp was reduced from 7.4 mmHg to 1.6 mmHg in the experimental group and was unchanged in the control group. Animals were examined regularly for a year. Reduced CSFp was associated with bilateral, progressive reduction in retinal nerve fiber layer thickness (RNFL) in two of four study animals, a disc hemorrhage in a third animal, and no changes in a fourth. Monkeys that demonstrated reduced RNFL also had reduced optic nerve rim area and increased optic nerve cupping. However, deformation of the lamina cribrosa was not observed. Control animals demonstrated no changes.

Several retrospective and prospective clinical studies support the role of reduced CSFp in POAG. Notably lacking have been chronic animal models to investigate this hypothesis.

This study suggests that chronically reduced CSFp produces RNFL thinning and optic nerve changes that are similar to those seen in GON. Longer-term observation and histological studies are needed to clarify the nature of this optic neuropathy and its relationship with glaucoma. The implications of this research, if confirmed, represents a major step forward in our understanding of the disease we call glaucoma.

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