Surgical sight restoration: A sticking point and treatment with alternating current.

Russian version

I decided to write this article after reading quite sad notification dedicated to a patient whose cornea was restored after longstanding blindness. In spite of operation successfulness, researchers observing the patient during 7 months after the operation, concluded that due to long-term visual deprivation the vision restoration may never be complete.

Being flurried with this unpromising news I decided to investigate whether any solutions may exist. Now I would like to share my findings with you.

Finding No.1: the issue does really exist.

One would think that the newly developed surgical techniques, such as corneal and limbal stem-cell transplantation, intraocular lens and artificial cornea implantation would have to solve the issue of complete visual perception restoration for the targeted patients. However what have turned out in fact? Studies of patients who underwent the restorative eyesight surgery after years of blindness do not give encouraging results. For example, Dr. Fine et al. studied the patient MM, who lost one eye at the age of 3,5 and was blinded in the other one after chemical and thermal damage to cornea [1]. This patient underwent the corneal and limbal stem-cell transplantation surgery when he was 43 years old. The surgery was successful and the patient gained acuity of 0,02 [2]. He could easily recognize simple shapes, identify colors and discriminate the direction of both simple and complex plaid motion [1].  In spite the patient regained the important vision functions; he still had low acuity performance even upon 2 years after surgery as well as difficulties with three-dimensional form, face, and gender recognition and interpretation [1].  Even 7 years after the operation, he still had poor spatial resolution and limited visual abilities [3].

With this regard it is worth to mention about the “critical period theory”. The critical period is a period of visual development when the visual stimuli are necessary for the visual function development. This theory was extended by researchers Dr. Lewis and Dr. Maurer, who noted that different visual functions have different sensitive periods of development [4]. Thus, in case the visual deprivation starts at 6 months of age, it prevents the development of normal acuity, but does not affect the sensitivity to the global direction of motion, which develops during the period near birth. 

Accordingly, Dr. Fine et al. supposed that MM had dissimilarities in visual function restoration because the ability to  interpret three-dimensional forms and faces develops after early development, while the ability to interpret motions is formed earlier in childhood [1]. Regarding the acuity it was concluded that long standing visual loss deteriorated the spatial resolution of the patient’s relevant visual cortex area. 

Another observation Dr. Ostrovsky et al. did while studying two congenitally blind children suffering from dense bilateral cataract [5]. The children gained partial vision restoration at the age of 7 and 13 due to intraocular lens implantation. As the result, after operation children had acuity of 0,2 and 0,25 and both could perform simple shape recognition. Nevertheless they still had poor but improved with time (during 10-18 months) recognition of overlapping simple shapes, i.e.  perceptual organization of the visual scene.

Thus, the theory about critical / sensitive periods may explain the partial visual function recovery after restorative eyesight surgery in patients who lost sight in the childhood. Nevertheless, how the similar issue may be explained when the vision loss happens in the adulthood?

Dr. Sikl et al. studied the subject who lost his vision at the age of 17 because of the explosion [6]. The patient’s cornea was damaged in both eyes. At the age of 71 he underwent an artificial cornea implantation. As the result, the patient gained acuity of 0,33. Upon 6 and 8 months post surgery he performed a good object recognition: 92% recognition of canonical form objects versus 20-30% demonstrated by early-blindness patients postoperatively. Also the patient differentiated face from non-face stimuli and successfully fulfilled simple tasks of visual space perception.  At the same time he still had difficulties with complex 3-dimentional visual scenes recognition, gender and two faces shown simultaneously differentiation, as well as limited ability to integrate partial information. A neuropsychological examination did not reveal any cognitive deficits and the patient’s performance matched his age.

As far as is known, the sensory substitution (e.g. spatial detection of sound, Braille reading) helps greatly to sightless individuals in their daily life. However, does this result of cross modal plasticity always have an advantageous impact?

Unfortunately, it does not. Dr. Dormal et al. investigated a patient whose vision severely deteriorated in childhood (during the age of 2,5-13 years) because of dense bilateral cataracts [7]. After artificial cornea implantation at the age of 47, the subject’s acuity improved from 0,04 up to 0,2 (1,5 months post surgery) and up to 0,7 (7 months post surgery). The researchers noted the contrast sensitivity and face individuation improvements (which though were still below the normal range). The activity of the visual cortex before and after the restorative eyesight surgery was monitored via functional magnetic resonance imaging (fMRI). The researchers noted that before the surgery visual cortex of the patient actively responded to audio stimuli. After the surgery the visual cortex still responded to audio input which overlapped with visual responses. Though the activation of visual cortex with sound was decreased post surgery, it still was recorded even 7 months after the surgery. In other words, the audio signals still competed with visual ones for being analyzed by visual cortex. In the researcher’s opinion it may explain why the patient’s visual performance still was below the normal level after the sight-restorative surgery.

According to all above mentioned, 

it seems that if the longstanding eyesight loss happens due to damage of anterior eye tissues, surgical restoration of the tissues is not enough to regain the visual functions to the full extent. Sounds quite pessimistic, isn’t it? 

It may well be not so sad if to come to understanding that the visual function loss is not restricted solely to the local tissue damage [8].

Finding No.2: applying of alternating current may partially return visual perception to sightless. 

After alpha band oscillations monitoring in both visually impaired and sighted subjects, Michal Bola et al. noted that visual function loss is accompanied with disturbance of brain networks synchronization (BNS). Moreover, the researchers came further and demonstrated that BNS may be adjusted with alternating current application. The method which was used by the researchers is called “noninvasive repetitive transorbital alternating current stimulation” (rtACS) wherein the stimulating electrodes are applied to the skin at the ocular region [8]. 

Formerly I have already written about this therapeutic approach. Treatment with rtACS leads to improvement of patients’ visual tasks performance. The success of rtACS was ascertained, particularly, by clinical observational study, where patients with optic nerve damage exhibited significant improvements in both visual field (by 9,3%) and acuity (by 0.02) after the treatment [9]. An explanation of such phenomenon was proposed by Dr. Sabel et al. within “residual vision activation theory” [10]. 

According to the theory, the visual system pathway usually is not damaged totally. There still exist some survived residual structures. Nevertheless they can’t provide proper transfer of visual information because the neuronal cell loss leads to neuronal network disorganization, i.e. to loss of network synchrony. Stimulation with rtACS forces the disorganized neuronal network to fire simultaneously. That restores the network synchrony of both survived cells within damaged region and cells of upstream visual pathway. Repetition of rtACS stimulation stabilizes the network firing synchrony. The mechanism involved is similar to one underlying the process of normal learning.

Notably that even patients considered to be “legally blind,” almost always have some degree of residual vision and therefore some restoration potential [10]. 

According to Dr. Sabel, the subject’s age, as well as age, type and location of the damage throughout visual system pathway do not influence the degree of visual restoration (it refers to injuries of nerve tissues, that is retina, optic nerve, brain regions). The only known parameter that matters for restoration, though, is the size and topography of areas of residual vision (ARVs). Vision restoration may be induced in most visual field impairments (scotoma, tunnel vision, hemianopia, acuity loss), irrespective of their etiology (e.g. stroke, neurotrauma, glaucoma, amblyopia, age-related macular degeneration). However, vision restoration is rarely complete and does not take place in all patients.

Sum of Findings No.1 and No.2: should we expect a light at the end of the tunnel?

Comparing of all abovementioned facts brought me to one presumption. Whereas noninvasive stimulation of visual system tissues with alternating current may improve visual perception even in patients whose blindness is caused by damage to the nervous tissues of the visual pathway. Probably, such approach could also help to the patients whose nerve tissues are not affected but because of the long term visual input absence the visual function restoration doesn’t happen completely. Definitely this is what should be investigated, but what if rtACS is what could help in rehabilitation of the patients after surgical vision restoration and allow them to regain the visual function to the full extent?

 

References:

1. Fine I, Wade AR, Brewer AA, May MG, Goodman DF, Boynton GM, Wandell BA, MacLeod DIA (2003). Long-term deprivation affects visual perception and cortex. Nat Neurosci 6: 915–916. DOI:10.1038/nn1102

2. Saenz M., Lewis L. B., Huth A.G., Fine I., Koch C.(2008). Visual motion area MT+/V5 responds to auditory motion in human sight-recovery subjects. J Neurosci. 28(20): 5141–5148. doi:10.1523/JNEUROSCI.0803-08.2008.

3. Heimler B et al. Revisiting the adaptive and maladaptive effects of crossmodal plasticity. Neuroscience (2014), http:// dx.doi.org/10.1016/j.neuroscience.2014.08.003

4. Lewis T. L., Maurer D. (2005). Multiple Sensitive Periods in Human Visual Development: Evidence from Visually Deprived Children.  2005 Wiley Periodicals, Inc., DOI: 10.1002/dev.20055.

5. Ostrovsky, Y., Meyers, E., Ganesh, S., Mathur, U., and Sinha, P. (2009). Visual parsing after recovery from blindness. Psychol. Sci. 20, 1484–1491. doi: 10.1111/j.1467-9280.2009.02471.x

6. Šikl R, Šimeček M, Porubanová-Norquist M, Bezdíček O, Kremláček J, Stodůlka P, Fine I, Ostrovsky Y  (2013). Vision after 53 years of blindness. i-Perception 4(8) 498–507; doi:10.1068/i0611

7. Dormal G, Lepore F, Harissi-Dagher M, Albouy G, Bertone A, Rossion B, Collignon O (2014). Tracking the evolution of crossmodal plasticity and visual functions before and after sight-restoration. Journal of Neurophysiology, 113, 1727-1742. doi: 10.1152/jn.00420.2014

8. Bola M., Gall C., Moewes C., Fedorov A., Hinrichs H., Sabel B.A.(2014).Brain functional connectivity network breakdown and restoration in blindness. Neurology 6, 542–551.doi:10.1212/ WNL.0000000000000672

9. Fedorov A, Jobke S, Bersnev V, Chibisova  A., Chibisova Y., Gall C., Sabel B. A. (2011). Restoration of vision after optic nerve lesions with noninvasive transorbital alternating current stimulation: a clinical observational study. Brain Stimul.4:189-201. DOI:10.1016/j.brs.2011.07.007

10. Sabel B.A, Henrich-Noack P., Fedorov A., Gall C. (2011). Vision restoration after brain and retina damage: The “Residual Vision Activation Theory”. Prog Brain Res, 192, 199-262. DOI: 10.1016/B978-0-444-53355-5.00013-0