RE-PERG not altered in retrograde Optic Nerve degeneration among patients with pituitary adenoma

PERG amplitude reduction, reversible after surgery, was also detected in microadenomas. It is well known that in cases of compression of the visual pathway, such as in pituitary adenomas, there is an early increase in VEP latency, followed by a reduction in the VEPs amplitude. It is also known that hemifield stimulation with a large check stimulus is more sensitive than full-field VEP in detecting chiasmal dysfunction.

As for PERG, it is initially normal and subsequently altered as neuronal degeneration occurs. PERG has been shown to be a practical prognostic test for visual outcomes in preoperative assessment compression of the optic nerve in pituitary tumors. Abnormal PERG correlates with a lack of postoperative recovery, presumably demonstrating significant retrograde degeneration of retinal ganglion cells. Both the reductions in the VEPs and PERG amplitude are due to the progressive loss of retinal ganglion cells (RGCs), the latter following the first.

Glaucoma is also commonly considered a form of optic neuropathy due to retrograde degeneration. Mechanical theory states that the raised IOP determines, at the level of the lamina cribrosa, mechanical stress and strain of the optic nerve, which can lead to interruption of the supply of neurotrophic factors to the RGCs and subsequently to RGCs loss. For this reason, PERG progressive alterations similar to those found in the experimental section of the optic nerve have been reported in animal models of glaucoma.

Authors Mavilio et al developed a new electrophysiological test, called RE-PERG, based on a modified SS-PERG sampled in five consecutive blocks of 130 events each. In this test, they evaluated amplitude, which is related to the number of living neurons, and standard deviation of the phase (SDPh), which is associated with the metabolic state of living neurons. It has been reported that phase variations are related to very early RGCs' dendritic dysfunction that may precede cell death. Such early RGCs dendrites degeneration has also been shown using scanning electron microscopy in the inner retina assessed to have a none-to-moderate loss of RGCs number in human glaucoma patients.

Considering PA as a model of retrograde degeneration similar to glaucoma, the aim of this work was to verify if RE-PERG findings are altered in case of retrograde degeneration and, therefore, if this test is altered only in the presence of primary neurodegeneration of RGCs.

Twelve PA patients and 14 age-matched HC were recruited. All participants performed visual field (VF) test, retinal nerve fiber layer (RNFL) and ganglion cells complex (GCC) thickness measurement by means of optical coherence tomography (OCT), visual evoked potentials (VEPs) and RE-PERG, a non-invasive, fast steady-state pattern electroretinogram (SS-PERG) sampled in five consecutive blocks of 130 events.

VEPs amplitude was significantly lower in PA with respect to HC (p=0.045). VEPs latency was higher in PA (p<0.01). As for VF, mean defect (MD) and pattern standard deviation (PSD) were higher in PA (−6.6±2.6 vs −0.01±1.02 dB; p><0.01 and 8.5±3.1 vs 1.5±0.3; p><0.01, respectively). RNFL thickness was lower in PA (88±8.1 vs 97±9.3 µ; p=0.01). There was no statistically significant difference between PA and HC for RE-PERG. There was a significant correlation among MD, PSD, VEPs amplitude, PERG amplitude and RNFL thickness in the PA group, whereas no correlation was found with SDPh, which remains as normal as in the HC group.>< 0.01). As for VF, mean defect (MD) and pattern standard deviation (PSD) were higher in PA (p< 0.01 and p< 0.01, respectively). RNFL thickness was lower in PA (p=0.01). There was no statistically significant difference between PA and HC for RE-PERG. There was a significant correlation among MD, PSD, VEPs amplitude, PERG amplitude and RNFL thickness in the PA group, whereas no correlation was found with SDPh, which remains as normal as in the HC group.

Study results confirm that, in patients with PA, consistent with MD, PSD and RNFL thickness values, VEPs amplitude was reduced, and VEPs latency was higher, as previously reported, whereas the PERG SD-Ph showed no difference between groups. Therefore, this study suggests that RE-PERG is not altered in the presence of retrograde degeneration.

Glaucoma is considered a form of retrograde degeneration of the optic nerve. In classical mechanical theory, the site where the raised IOP exerts its pathological function is the lamina cribrosa (LC), in which observed a mechanical strain and, as a consequence of this, increasing cupping or depth, and development of focal defects. It has been shown that strain is eye-specific and mediated by intraocular pressure, cerebrospinal fluid pressure, scleral and lamina cribrosa morphology, and structural stiffness.

It is still unclear if all these pathogenetic mechanisms are a direct consequence of IOP rise but not related to the stress of lamina cribrosa or are a product of the same metabolic alterations that lead to IOP rise or, finally, are totally independent of IOP (such as in normotensive glaucoma). Whatever the cause, based on the current literature and on the outcome of the present study, in glaucoma, there are two coexisting mechanisms of RGCs damage: a retrograde degeneration starting from the lamina cribrosa, and primary neurodegeneration of the RGCs' cellular soma, the latter being identified by RE-PERG as an increase of SDph.

Source: Mavilio et al; Clinical Ophthalmology 2022:16 https://doi.org/10.2147/OPTH.S384525