May open angle glaucomatous disease (OAGD) be considered a neuro-ophthalmological entity?

Abstract

Open-angle glaucomatous disease (OAGD)-type field loss may run in families with optic neuropathy, ganglion cell damage, and normal hydrodynamics. Recently, patients have been observed with moderately elevated intraocular pressure (IOP) and an absence of functional defects, except for disturbed foveal flicker fusion for the descending green mode, characteristic of a retinal magnoganglion cell impairment. Individuals who received no IOP-lowering treatment developed field defects later on, while those with normal foveal flicker fusion (FFF) tests for the descending green mode did not develop field changes, even without any IOP-lowering treatment. Histopathology of the complete optic pathway of advanced OAGD revealed pronounced but not total retinal ganglion cell loss. At the level of the simple ascending atrophic optic nerve, however, axons were observed with preserved myelin sheaths, proof that not all ganglion cells were lost, whereas the primary cause of total ascending optic atrophy can only be explained in OAGD by transsection of laminar optic nerve axons, due to impaired capillary output. Thus, changes in FFF frequencies appear to be the earliest functional hallmark in OAGD, while ophthalmoscopy under red-free light reveals loss of peripapillary axons as the first anatomic hallmark of OAGD optic neuropathy. Neuroprotective treatment has been reported to be beneficial. Faulty control of apoptosis (susceptibility factor) in some retinal ganglion cells before clinical symptoms develop may be the cause. The loss of ganglion cells occurs more rapidly in the presence of a relatively high IOP. Ultrastructural changes in guinea pig optic nerves have been reported after the experimental acute increase of IOP. In order to determine if the damage to some ganglion cells was due to the direct effect of the increased IOP or to a vascular stealing phenomenon, we repeated the experiments in birds (chickens) of which it is known that there is no vascular supply to the retinal ganglion cells. Progressively elevated IOP of different duration resulted in the appearance of an apoptotic look of some ganglion cells; when the duration of IOP elevation was longer, more cells were damaged. Additionally, a necrotic look appeared, while axons at the laminar level were rather mildly affected. Therefore, a different sensitivity of ganglion cells to the direct mechanical effect of IOP elevation appears to be likely. Besides the impairment of the choroidoscleral outflow damaging the axons, a more seriously damaging effect of raised IOP to some ganglion cells has to be considered in humans expressing the apoptotic p 53 gene before clinical symptoms develop.The ascending mode may be preponderant, acting simultaneously with the descending mode, but it must be emphasized that primary impairment of some retinal ganglion cells may be most probable.