We enrolled 13 individuals in this study. The results showed that there were no subjects with any complaint of discomfort. The IOP and BCVA were not obviously changed. The global MD was improved significantly, consistently the global MS increased after training. And we may conclude that optic nerve damage due to glaucoma had potential plasticity.
Serious optic nerve damage, which resulting from optic neuritis, ischemic neuropathy, glaucoma, photoreceptor degeneration, and trauma, was generally considered irreversible. In the latest decades, more and more studies reported that the nervous system even mature mammalian showed astonishing adaptability, which was known as “neuroplasticity” or “neurological rehabilitation”[11, 12]. In the 1980s, a famous deafferentation study introduced that topographic cortical representations are maintained dynamically throughout life in primates[8]. Lately, spinal cord injury patients with disabilities standing up were reported by several different research teams[22–24].
Traditionally, for glaucoma patients, the major choice was to control IOP including medical or surgical treatments. Besides, there have been auxiliary treatments such as eye yoga exercise which had been mentioned with limited outcomes recently[14]. Based on the new understanding of neural plasticity, we found that after the vision restoration training period, the global MD improved significantly, and the global MS also changed better in this study. It was supported by the report that primary open angle glaucoma (POAG) with visual field defects was improved by systematic vision stimulation, even in the training-free intervals[18]. Further research also demonstrated that significant detection accuracy gains, faster reaction time, health-related quality-of-life mental health domain increased in glaucoma patients[19].
Except the glaucoma-related visual damage, neuropathy induced by other diseases also can be improved. Patients with retro-chiasmatic injuries underwent visual rehabilitation training, the visual reaction time was significantly shortened, and visual improvement was significant[25, 26]. Sabel and his colleagues reported a 27 years old patient with massive facial injury and brain damage. Only 10% visual field index (VFI) left in his left eye, after neurological rehabilitation training, VFI finally improved to 74%[16].
An obvious question was, why mature neurons remain had the ability of neuroplasticity? The mechanism remained elusive. In glaucoma patients, the retinal region corresponding to the scotoma of the visual field, viable RGCs exist with irregular or swollen cell bodies, smaller and shorter dendritic processes[27], which may retain their dendritic plasticity[28]. In the optic nerve crush model, 70 ~ 90% of RGCs underwent degenerative changes, few cells retained, however approximately 80 ~ 90% of vision function restored within 2 ~ 3weeks[29]. And further research demonstrated these surviving cell bodies moderately enlarged which may undergo neural remodeling[29, 30]. Besides, sabel had proposed the “residual vision activation theory” which meant that in the damaged visual pathway, in addition to normal and dead RGCs there were some “dormant” nonfunctional living cells[31]. These dying cells unable to produce clinically visible functional activity, may have the ability to modulate peripheral sensory-motor neural networks, providing an anatomical basis for functional remodeling[24]. In this study, the global MD improved significantly, and the global MS also changed better, mainly because of the visual stimulation located at the visual field damage or its border region[17–19].
After the tVRT, none of these participants complained of uncomfortable during the training period. Sabel and his colleague applied the rtACS to restore residual vision[19]. In their study, some adverse events such as transient vertigo, mild headache, cutaneous sensation, back pain and stiff neck occurred, and a few participants dropped out of the study[9]. Besides, trans-corneal electrical stimulation was also used in patients with ischemic optic neuropathy[10], but it was mostly preferred in animal experiments[32–34]. In this study, the subjects were trained with a computer terminal based on an augmented virtual reality platform without any invasive stimulation, which was much safer than rtACS or other trans-corneal electrical stimulation. And it had been successfully displayed in children with intermittent exotropia and normal population without eye diseases[35, 36].