Paolo Giuseppe Limoli and Marcella Nebbioso
NEUROMODULATION AND VISUAL REHABILITATION
THE ROAD TO VISUAL NEUROENHANCEMENT IN THE VISUALLY IMPAIRED PATIENT
With the collaboration of Andrea Antal, Chiara Berna, Irene Casaro, Stefano Casaro, Lorenzo Casillo, Ayoub Chabib, Ilaria Ciochetta, Laura Contento, Riccardo De Corato, Francesca De Rossi, Socrates Dokos, Giuliana Facciolo, Enrico Fermi, Arianna Gagliardi, Ying Gao, Maurizio Giannelli, Tianruo Guo, Chiara Iacovacci, Saar Kariv, Edward Kondrot, Liming Li, Nigel H. Lovell, Marco U. Morales, Giuseppe Napolitano, Matthew A. Petoe, Nader Pouratian, Daniel L. Rathbun, Erika Rigoni, Bernhard Sabel, Giovanni Sato, Sergio Z. Scalinci, Mohit N. Shivdasani, Stefano Tricarico, David Tsai, Elvire Vaucher, Gianfrancesco Villani, Enzo M. Vingolo
Paolo Giuseppe Limoli and Marcella Nebbioso
Neuromodulation and Visual Rehabilitation
The road to visual neuroenhancement in the visually impaired patient
With the collaboration of Andrea Antal, Chiara Berna, Irene Casaro, Stefano Casaro, Lorenzo Casillo, Ayoub Chabib, Ilaria Ciochetta, Laura Contento, Riccardo De Corato, Francesca De Rossi, Socrates Dokos, Giuliana Facciolo, Enrico Fermi, Arianna Gagliardi, Ying Gao, Maurizio Giannelli, Tianruo Guo, Chiara Iacovacci, Saar Kariv, Edward Kondrot, Liming Li, Nigel H. Lovell, Marco U. Morales, Giuseppe Napolitano, Matthew A. Petoe, Nader Pouratian, Daniel L. Rathbun, Erika Rigoni, Bernhard Sabel, Giovanni Sato, Sergio Z. Scalinci, Mohit N. Shivdasani, Stefano Tricarico, David Tsai, Elvire Vaucher, Gianfrancesco Villani, Enzo M. Vingolo
Fabiano
Publisher For Vision 2025 – Florence - Italy
© Copyright 2025
ISBN 978-88-31256-83-4
FABIANO Gruppo Editoriale
Editore
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Paolo Giuseppe Limoli
Degree in Medicine and Surgery and Specialization in Ophthalmology at the University of Milan. Scientific coordinator of the Low Vision Research Center in Milan, medical director of the Eye.com Eye Center in Palermo, Scientific Secretary of the Low Vision Academy from 2006 to 2022, LOC President for Vision 2025, member of the scientific council of the Federazione Italiana Retina e ipovisione (FIRI) and member of the Association of Research on Vision and Ophthalmology (ARVO). His research is oriented towards retinal neuroenhancement through autologous cell implants, mesenchymal secretome, neuromodulation and visual rehabilitation.
paololimoli@libero.it
Marcella Nebbioso
Ophthalmologist and President of the Low Vision Academy from 2022. Currently, She is an associate professor of diseases of the visual system and works at the Department of Sense Organs, Sapienza University of Rome. Her research primarily focuses on the field of ocular electrophysiology, oxidative changes associated with retinal diseases, and the potential for restoration through cell-mediated therapies. Her ongoing project centers on 'Retinal regeneration techniques and vernal keratoconjunctivitis biomarkers. He has published countless international scientific papers (PubMed) and books on the visual system.
marcella.nebbioso@uniroma1.it
The book, written to improve “vision”, is dedicated to
all the ophthalmologists that wish to learn about the possible ways to recover sight when “there’s nothing more to do”
all the researchers who are committed to discovering and tracing these ways with daily efforts and possible frustration
all the visually impaired patients who could eventually have a map that shows them the correct way, avoiding blind alleys and wrong directions.
Lastly, I would like to thank Professor Rita Levi Montalcini, who, with her strength of spirit and dedication to research, has given me the motivation to delve deeper and continue my studies on patients suffering from serious eye diseases
Paolo G.
Limoli
SECOND
THIRD
Chapter 22 - Giannelli
FOURTH PART
Vision beyond the retina: prosthetics and optogenetics
Chapter 23 - Guo, Tsai, Petoe, Li, Rathbun, Dokos, Lovell, and Shivdasani
Chapter 24 - Kariv and Pouratian
Stimulation of visual cortex in blind subjects with Visual cortical prostheses:
FIFTH PART
SIXTH PART
Preface
Fabiano Publishing, through the Low Vision Books series, has strongly committed to increase the literature available in the field of low vision, filling-in the gaps and opening new perspectives. In this case, there is a strong commitment to translate the scientific research in critical areas of retinal pathology into neuro-modulation strategies that can be applied to clinical practice. And thus, this book aims to become a reference for the professionals in the field.
Dr. Limoli has a long history of study and application of neuro-modulation to low vision. In this book, he is at the lead of a large group of Co-authors of high scientific profile. Their work is a synthesis of the procedures of neuro-modulation that today we can apply in low vision.
“Neuromodulation” is not an awkward word that flies over our heads, too complicated to get into terms with. Instead, it is a flexible, reversible, and customizable approach that implies the modulation of neuro-transmission both at the central and peripheral level, typically through electrical and biochemical impulses. It has found therapeutic applications in neurology, psychiatry, neurology, and cardiology, among others. Neuromodulation in low vision opens new horizons also in the field of ophthalmology.
Even though the incidence of retinal pathology is high and the pathophysiology involved is complex, numerous neuroprotective treatments are promising and give hope to move new steps forward in order to avoid further vision loss. Neuro-protective strategies aim to promote neuronal survival, to prevent the death of retinal cells, and to pave the way for new modalities of cellular interaction. In rehabilitation, the goals are to increase the mechanisms of endogenous repair through the modulation of the biological signal, exercise, and electrical stimulation (1).
It is important to remember how experimental studies have provided and still provide the basis for assessing the safety and the therapeutic potential of such strategies. For instance, electrical neuro-simulation applied through electrodes into the subretinal space as shown beneficial for the outer retinal layers that are damaged in the case of photoreceptor degeneration (Pardue, 2018). Experimental models also showed that neuro-stimulation can elicit a cortical response similar to that one elicited by a standard light stimulus (2). And again, chronic low voltage electrical neuro-stimulation has proven protective for retinal cells (Chow, 2004; 1). A recent study on rats with retinal degeneration which were electrically stimulated twice a week through an electrode placed in the supra-choroidal space has shown the possibility to preserve the retinal function as shown on the ERG, and to protect the outer nuclear layer as shown by histological examination because such layer appeared thicker in the animals which were stimulated compared to controls (Abbott CJ, 2019).
The clinical applications associated to the progress of scientific research are as well the focus of interest and potentiality. Neuroprotective strategies promote the survival of neurons. The neuro-modulation of the biological signals fosters new cellular interactions that support the visual function promoting personal independence and a better quality of life.
Dr. Limoli and his Co-authors will lead us into this engrossing trip into neuro-modulation applied to low vision.
Gianfrancesco
Villani
Preface
BIBLIOGRAFIA
1. Pardue MT, Allen RS. Neuroprotective strategies for retinal disease. Prog Retin Eye Res. 2018 Jul;65:5076. doi: 10.1016/j.preteyeres.2018.02.002. Epub 2018 Feb 23. Review.
2. Chow AY1, Chow VY. Subretinal electrical stimulation of the rabbit retina. Neurosci Lett. 1997 Mar 28;225(1):13-6.
3. Chow AY, Chow VY, Packo KH, Pollack JS, Peyman GA, Schuchard R. The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa. Arch Ophthalmol. 2004 Apr;122(4):460-9.
4. Titchener SA, Ayton LN, Abbott CJ, Fallon JB, Shivdasani MN, Caruso E, Sivarajah P, Petoe MA.Head and Gaze Behavior in Retinitis Pigmentosa. Invest Ophthalmol Vis Sci. 2019 May 1;60(6):2263-2273. doi: 10.1167/iovs.18-26121.
Pourpose of the work
Low vision is still a little known area of ophthalmology and requires constant study, a multifactorial approach, multiple skills and a two-way dialogue with the other sectors of the ophthalmological discipline.
The lack of communication among experts hampers a higher level of cognition about this topic.
This volume, in the philosophy of Low Vision Books, deals analytically with two fundamental aspects with which rehabilitation operators must measure themselves: neuro-enhancement and neuro-modulation.
The claim that a patient affected by retinitis pigmentosa cannot improve his visual condition because "there is no cure”, or that a patient with maculopathy and central scotoma cannot wear glasses to see better because the damage is irreversible by now, does not take into account the neuro-strengthening mechanisms available both at the retinal and cortical level, as well as along the nerve conduction pathways, in order to stabilize retinal functionality, fixations and the overall visual perception.
The knowledge of the ocular, cerebral and vascular co-factors that are at the base of the vision and the strategies to have an adequate interaction among these components, helps the patient to improve the modalities with which the retinal image is captured and then transferred as electrical micro-impulses in order to be received and inter-
preted at the cortical level.
It is possible to boost visual perception by stimulating neurogenesis and improving blood flows, both at retinal and cerebral level.
A patient with visual impairment can be tranformed into one with a better sight, pleased with himself and the care received and more integrated with the society in which he lives.
It is not just a question of applying an optical aid to enlarge a sequence of characters. The main goal is to have a neuro-enhancement of the residual visual function, through medical, rehabilitation and surgical techniques.
Namely, the purpose of this text is to analytically evaluate the various techniques able to modulate the nervous system functions, to finally improve the perception of the signal.
The neuro-modulation can be obtained using techniques that seem to be very different: neuro-micro-electric stimuli at retinal and / or cerebral level, pulsed stimulations obtainable with optical patterns at determined frequencies, flicker stimulations, microperimetric biofeedbacks.
Complex systems can be carried out in special centers while simpler systems can be done in a domestic environment.
Despite it has been little known until recently, neuro-modulation accounts for a tool that will revolutionize the concept of visual rehabilitation in the near future.
Paolo G. Limoli and Marcella Nebbioso