Glaucoma, as stated before, in the world is a leading cause of acquired blindness, in most advanced cases, presence of scotoma involving the fixation area usually becomes relevant. Visual function in glaucoma patients is usually evaluated with basic visual acuity and static computerized perimetry with dedicated strategy. Both tests in our opinion, in late stages of the disease, are incomplete to investigate aspects of macular function, visual field, because the location and number of points, might not be adequate to detect small scotoma located around the central foveolar area and in advanced glaucoma unstable fixation affects reliability of test results. In late glaucoma stage a deep loss of retinal sensitivity produces significant impairment and functional symptoms that step into low vision area ad have as a further evolution blindness.
Microperimetry and rehabilitative tools was already used in literature with the aim to diagnose and improve fixation stability in patients with several retinal diseases. In advanced glaucoma, may be possible obtain good results with MP-3 microperimetric biofeedback, with the goal to activate and train new PRL to improve several functional parameters as: fixation stability, BCVA, reading speed and consequently quality of life. Investigating fixation patterns in glaucomatous patients Takanori et al. (2009) using the MP-1 microperimeter in 39 eyes with advanced glaucoma concluded that was possible individuate specific fixation patterns and scotoma maps of retinal sensitivity in eyes with glaucoma with a strict correlation with optic nerve head conditions.
Techniques of Biofeedback were applied to vision (Mezawa et al., 1990) and still now, considering methodological and physiological aspects, are investigated by several authors (Vingolo et al., 2009a; Contestabile et al., 2002; Giorgi et al., 2005;). Different visual rehabilitation devices that use different strategies of fixation are proposed for biofeedback purpose. These devices were developed in the past century like “Accommotrack Vision Trainer” (The Nasa Connection, Seattle, WA) a very basic instrument that allowed low level fixation control and few programs dedicated to low vision patients. More complex devices were developed in the late nineties and early 2000, these instruments were characterized by integrated high level of eye tracking with biofeedback system fundus related MP-1 microperimeter (NIDEK Technologies Srl, Padua, Italy), or the MAIA2 (Centervue Padua Italy). Others were based on electrophysiological control of fixation obtained by steady state VEP (visual trainer LACE instruments).
Biofeedback training used in different diseases, was supposed obtain better visual performances facilitating neural transmission involving intraretinal neurons and interneurons connections between the retina and brain, supporting a “remapping phenomenon” as described from several Authors (Alpeter et al., 2000; Buia and Tiesinga, 2006). Andrade et al. (2001) these Authors demonstrated that glaucoma patients in their vision, frequently do not have perception of the scotoma, because, in case of optic pathway damage, cortical receptive fields originating from this region are not inactive but show more sensitivity to stimuli localized in surrounding areas, by the mean of connections driven by horizontal cells in the inner layers of the retina, geniculate area and cortex.
Two distinct steps, characterize this phenomenon with different time scale: a) a redistribution of receptive fields (RFs) in the area of the lesion, and b) a progressive enlargement of neuronal fibers projecting in areas surrounding the scotoma, resulting in a new visual field configuration. Although the gradual rearrangement mechanisms are becoming more evident in the literature, several authors underline visual pathways rearrangement during the training, driven by an increase in synapses number, faster interneurons mediators and neurotransmitter reuptake, the trigger and first step of this process remains still unclear.
Position of glaucoma lesions projected in the retinal area as corresponding to the scotoma, send some kind of activity, from the undamaged neurons, to cortical surrounding neurons located in the area the lesion (Andrade et al., 2001). The brain is able to modify itself, for intrinsic cortical plasticity, to adapt to new background modifications depending to damage of the neural system. This author also underlies the learning and attention processes involved in this rearrangement. Safran and Landis (1996) stated that, “Cortical changes occurring after focal visual differentiation modify visual perception by filling in visual field defects with information from the area surrounding the scotoma”.
These processes cause, in glaucoma subjects, tendency to underestimate their defects, distortion in spatial perception, in visual field amplitude or in cortical plasticity. Sum of effects can delay patient’s detection and identification of visual field defects, and consequently the treatment, meanwhile also affecting perception and outcome of some diagnostic procedures (Safran and Landis, 1996).
Auditory biofeedback, as found by Mezawa et al. (1990), were applied in treatment congenital nystagmus, patients reported at the end of training, a subjective sensation of better vision and improvement of foveation time, VEP amplitude, and threshold spatial frequency. Visual training effects of auditory biofeedback have also been studied in myopia to improve visual acuity (Rupolo et al., 1997; Vingolo et al. 2013, Angi et al., 1996,). another technique based on fundus related perimetry (microperimetry) with Scanning laser ophthalmoscope (SLO) provides functional results by direct visualization of the macular area.
Results of this method underline a correspondence point-to-point between fundus images and retinal sensitivity threshold. Instability of fixation, usually observed in static computerized perimetry, is a possible misleading factor that can result in difficult to interpreter findings, especially in eyes with low visual acuity or blindness. SLO microperimetry allows an accurate, direct and on line visualization of the stimuli when and where they are presented on the retinal surface, with a very short distance between two single stimulated points (less than 30’ instead 3° of standard computerized perimetry): this ultimately allows high accuracy in fixation monitoring and correlation directly between anatomo-pathological features and retinal function (Varano and Scassa,1998).
Rudimentary techniques of auditory Biofeedback were originally used for the treatment of different forms of ametropia (myopia, astigmatism, and presbyopia), nystagmus and amblyopia (Trachtman, 1978; Leung et al., 1996).
In our previously presented studies (Vingolo et al., 2009a; Vingolo et al., 2007;) we have underlined that in rehabilitation strategies of low-vision patients biofeedback with MP-1 is really efficient in patients with different diseases involving the posterior pole (age-related macular degeneration, vitelliform dystrophy, Stargardt’s disease, myopic macular degeneration, post-traumatic macular scar, cone dystrophy) reporting improvements visual performances (visual acuity, fixation behavior, retinal sensitivity and reading speed) and confirmed by Pacella et al., 2012.
Visual biofeedback training using the Visual Pathfinder (LACE Inc., Rome) was investigated by other authors in patients with high myopia evaluating VEP output, this study demonstrated improvements in visual performances (BCVA, fixation stability and retinal mean sensitivity, amplitude of the main peak of the pattern VEP). This functional training improved visual performances and consequently better quality of life, with a positive psychological effect on these patients that frequently present a depressive trait (Cannata et al., 2009).
Patients with retinitis pigmentosa were also treated with MP-3 and Visual Pathfinder rehabilitation, and in this case was shown that a stimulus with flickering pattern can increase visual acuity and VEP amplitude more than plain luminance stimulus, probably receptive field stimulated by the alternance of black and white checkerboard were potentiated, allowing an easier rearrangement of signaling originating from the surviving retinal rod-photoreceptors (Vingolo et al., 2009b).
As more elaborated Auditory biofeedback, instead driven by a luminous target pointed on a training retinal location (TRL), by a pattern stimulus (a flickering black and white checkerboard activated when patient’s fixation is pointed on a defined TRL) were evaluated in age-related macular degeneration patients (Vingolo et al., 2013). Both groups, in comparison with the baseline, showed better visual performance after rehabilitation but the biofeedback with pattern flickering stimulus was found to be significantly better and faster in training the patients to reach their PRL compared with the standard one. In the Authors opinion this suggests that, in the damaged retina, neuronal plasticity might override dead photoreceptor and outer retinal layers involving residual inner retina layers rich in surviving cells, to obtain signal amplification and integration at retinal and/or cortical level.
After visual training techniques improvement mechanisms of visual function may be controversial and various hypotheses can be advanced, in our opinion one of the most relevant is better coordination in oculomotor control and “searching capacity”.
Use and improvements in eccentric fixation due to the conditioned reflexes determined from the auditory peak could also be a mechanism (Trachtman, 1994). In our opinion, it is very relevant consideration that the improvement in visual function, mainly depending from foveation time, could be obtained after the training as a result of better ability for the patients to manage their residual visual function and reach or maximize full potential.
Residual vision activation theory was suggested by Sabel et al. (2011) to explain in which way the system may reactivate or restore visual function. In early 2000 was proposed a new technique: vision restoration therapy (VRT) as complementary treatment for AMD or Diabetic Macular edema; VRT involves a specific pattern of visual stimulation, directed at the border of the scotoma and the blind field, training this seen/not seen search may finally result in expansion of visual fields in individuals with brain or optic nerve injury as reported by Kasten and Sabel, 1995: Kasten et al., 1998. Romano et al. (2008). These papers demonstrated improvement in detection of stimuli and BCVA with VRT daily sessions. Measuring with suprathreshold visual field testing, resulted a shift of the position of the border of the blind field. So that the authors conclude that VRT is a useful intervention for rehabilitation in some patients with visual field defects from retro-chiasmatic ischemic lesions.
Restore vision and reduction of the scotoma extension can be achieved, but these results are related to the residual tissues and their activation state. Training unfortunately does not lead to permanent changes, interrupting biofeedback causes slow regression in performances, maintaining these levels of visual functions, require repetitive stimulation, possibly over days weeks or months in relationship to the deepness of the defect.
Changes in visual performances are partly determined by psychophysical and subjective variables as learning effect, motivation, level of attention, psycho-physical capacities, type of environment and influence of the examiner (Carpineto et al., 2007) so there is a need of high compliance by the patient.
Age, as frequently reported in the literature (Pache and Flammer, 2006: Steigerwalt et al., 2012; Nebbioso et al., 2011), is the major risk factor for glaucoma because degeneration of the retinal ganglion cells (RGCs) and its consequence of optic disk cupping characterizes all patients as clinical finding and this phenomenon has been compared to the visual impairment seen in patients with Alzheimer’s disease in which very often is associated undiagnosed findings of glaucoma. Also RGC death or optic nerve fiber degeneration may be present as part of biological mechanism very similar in most degenerative diseases of central nervous system (Kirby et al., 2010). New findings in recent paper have proven glaucoma-like axonal damage until the lateral geniculate nucleus and visual cortex from can (Gupta et al., 2006). This suggest, in our opinion, that glaucoma could be responsible of reduced visual performances as single visual field defects in patients affected by dementia moreover this thought suggests that developing an integrated approach with an interdisciplinary involvement, may lead to discoveries at different levels and underlines how favoring the connections between different specialties push forward the research, (D’Angelo, 2012).