Residual vision activation and the brain-eye-vascular triad: Dysregulation, plasticity and restoration in low vision and blindness - a review

Abstract

Vision loss due to ocular diseases such as glaucoma, optic neuropathy, macular degeneration, or diabetic retinopathy, are generally considered an exclusive affair of the retina and/or optic nerve. However, the brain, through multiple indirect influences, has also a major impact on functional visual impairment. Such indirect influences include intracerebral pressure, eye movements, top-down modulation (attention, cognition), and emotionally triggered stress hormone release affecting blood vessel dysregulation. Therefore, vision loss should be viewed as the result of multiple interactions within a "brain-eye-vascular triad", and several eye diseases may also be considered as brain diseases in disguise. While the brain is part of the problem, it can also be part of the solution. Neuronal networks of the brain can "amplify" residual vision through neuroplasticity changes of local and global functional connectivity by activating, modulating and strengthening residual visual signals. The activation of residual vision can be achieved by different means such as vision restoration training, non-invasive brain stimulation, or blood flow enhancing medications. Modulating brain functional networks and improving vascular regulation may offer new opportunities to recover or restore low vision by increasing visual field size, visual acuity and overall functional vision. Hence, neuroscience offers new insights to better understand vision loss, and modulating brain and vascular function is a promising source for new opportunities to activate residual vision to achieve restoration and recovery to improve quality of live in patients suffering from low vision.

Keywords: Glaucoma; brain; optic neuropathy; plasticity; recovery; vascular dysregulation; vision restoration.

Figures

Fig. 1.

Residual functions and subtle deficits in visual fields. Visual fields are not just black and white (blind and seeing fields) have “shades of grey”: hidden potentials with residual vision but also hidden problems in the “intact” sector. Blindsight is the phenomenon that patients are able to correctly guess that stimuli were presented without being aware of them. While correctly responding to vision signals, they report seeing nothing; unconscious seeing without knowing. Areas of residual vision are those with uncertain responses where patients respond only occasionally. These regions of the visual field are quite variable during repeated testing and are characterized by increased thresholds and longer response time. The hidden deficits in the “seeing field” make patients “sightblind”, but this can only be measured by tests that are sensitive to higher cognitive dysfunctions.

Fig. 2.

The brain-eye-vascular triad. This triad illustrates the interdependency of the three organ systems and their role in vision loss. The retina, which transforms light rays to electrical cell signals weighs only about 1 gram. But the estimated weight of the brain areas needed to support normal vision is on the order of several hundred grams. To understand the causes and consequences of vision loss, and to find new treatment options, the eye and the visual system cannot be viewed in isolation but rather need to be considered within the holistic context of different systems throughout the brain and vascular system. The arrows indicate the direction of interaction between brain (b), vascular system (v) and eye (e). The eye-brain influence is denoted as E2B (eye-to-brain) and B2E (brain-to-eye or brain-to-central visual structures). Such interactions can be direct or indirect. Note: blood flow is not only important for delivering nutrition / oxygen and removal of metabolic by-products, but it is also important for thermo-regulation when the eye is exposed to extreme heat or cold. IOP is at least in part regulated by the brain.

Fig. 3.

Emotional stress and the “Flammer Syndrome”. The term Flammer Syndrome (FS) describes a phenotype characterized by the presence of primary vascular dysregulation with a cluster of additional symptoms and signs. Symptoms and signs include the following: prolonged sleep onset time, prolonged blood flow cessation in the finger capillaries after cooling, disturbed autoregulation of ocular blood flow, increased prevalence of optic disc hemorrhages and activated retinal astrocytes, increased retinal venous pressure, increased stiffness of retinal vessels, higher spatial irregularities in retinal vessels, increased resistance in retroocular vessels, increased oxidative stress, altered gene expression as measured in lymphocytes, and altered activity of the autonomic nervous system (beat-to-beat variations of the heart).

Fig. 4.

The brain’s network to control vision. Many structures of the brain need to interact synchronously to execute visually elicited performance. The vision network is comprised of the retina, subcortical structures, and cortical areas of the brain with multiple interactions with each other. This graph depicts some of the most important brain regions and their presumed functions. The structures and some of their main functions are depicted in Table 2.

Fig. 5.

Residual vision and brain network amplification. (A) This graph serves only as a conceptual guide to appreciate the nature of residual vision and the interactions of retina and brain by neuronal oscillatory activity. Accordingly, vision loss (e.g. measured by detection ability) depends on how many cells are lost: the greater the cell loss, the greater is the defect in different regions of the visual field. Areas of residual vision (ARVs; shown in grey) correspond to regions of partial damage with or without vascular dysregulation. They are found in all kinds of visual field defects such as after stroke (e.g. hemianopia) or retinal or optic nerve damage (e.g. glaucoma). Black areas represent complete damage. Note, however, that many black regions may, in fact, have some residual visual function as well. (B) Whether or not visual stimuli processes by the retina are consciously perceived by the brains is not only determined by the strength of the neuronal signals sent by the retina to the brain, but it also depends on how the brain processes this information through synchronization, amplification and interpretation. Neural activity of the retina is represented here by a simple sine wave. If the brain network is disorganized (illustrated here by non-synchronized, out-of-phase brain sine waves), the sum of retinal and brain signals is too low to surpass the perceptual threshold and the visual stimulus is not perceived. When the brain is synchronized, this elevates (amplifies) the same residual visual signal to above-threshold perception, thus improving or restoring conscious vision.

Fig. 6.

Brain functional network reorganization. Healthy subjects have a strong functional connectivity network between occipital and frontal regions of the brain. But in patients with visual field defects this network is lost. When treated for 10 days with alternating current stimulation, this network is partially restored (Bola et al., 2014). Lower panel: As the brain functional connectivity recovers, so does the visual field (shown here with supra-threshold campimetry) (Sabel, 2016).

Fig. 7.

Activating residual vision. Examples of visual field recovery of three patients before and after treatment with alternating current stimulation (ACS); Top and middle panel: visual fields of a case with diabetic retinopathy and open-angle glaucoma before and after 10 days. The visual fields on the bottom is from a 27 year old male suffering from traumatic brain and optic nerve damage before and after 10 days of ACS with an additional 3 months of relaxation and eye yoga exercises. Note that visual field recovery emerges mostly from the grey regions (relative scotomas or “areas of residual vision”). Red circles indicate regions of vision recovery.