In 2023, Esme’s Umbrella ran a CBS Essay Prize for Medical Students and Optometry Students.

The winners were:

Fortunately, as a doctor, Eric knew this was not the case. Forty years prior, he had been diagnosed with glaucoma, a disease that damages the optic nerve and leads to loss of vision. Though he had undergone treatment at the time, his vision had gradually deteriorated and by 2013, he was entirely blind in his right eye with extremely limited vision in the left. Three years later, he began to see the startling visions of coloured fog and was diagnosed with Charles Bonnet Syndrome (CBS).

CBS is a neurological condition characterised by the occurrence of vivid visual hallucinations in patients who have often previously suffered some damage to their visual pathway at the level of the eye or higher centres in the brain2. The syndrome was first documented in 1760 by the Swiss scientist, Charles Bonnet. He reported that his grandfather, who had undergone cataract surgery in both eyes eleven years prior, had begun to develop dynamic coloured visions of men, women, birds, buildings, carriages and tapestries3. Patients with CBS cannot hear, smell, taste or touch any of their hallucinatory visions and are in fact, usually aware that what they see is not real4. The hallucinations that appear can range from simple images such as the fog that appeared in front of Eric, to complex scenes such as the plethora of objects seen by Bonnet’s grandfather5.

Since 1760, many more cases of CBS have been reported. Indeed, it is a relatively common disorder, affecting 1 in 5 people with poor vision and close to 50 million people worldwide6. Despite this, awareness of the condition is low within the patient population and even amongst the treating physicians7. A likely reason for this is one alluded to earlier; many sufferers are afraid of revealing their hallucinations for fear of being labelled mentally unstable2.

What causes these people to hallucinate?

One promising theory posits the idea of a ‘release’ mechanism triggered by sensory deprivation8. According to this hypothesis, loss of visual input disinhibits higher visual association centres, resulting in inappropriate patterns of neural excitation that give rise to ‘phantom vision’. This was explained elegantly by the eminent neuroscientist, V.S. Ramachandran9, using the example of a cat.

When we see a cat, it is the physical attributes (shape, size, colour, texture) that are captured in the retina of our eye. This information is split into visual processing streams that reach the primary visual cortex (V1) in the brain. It is then combined and analysed in higher processing centres to allow us to identify and recall the cat. However, when we imagine a cat, it appears that this information flow is reversed. We use our memories of cats and all their associated attributes from higher visual processing centres to influence the activity of V1. It is the interaction and activation of these areas in a top-down approach that allow us to ‘see’ an imaginary cat in front of us.

Ramachandran suggests that the line between seeing and imagining becomes blurred in a CBS patient. In a typical person, imagining a cat does not equate to ‘seeing’ the cat. This is due to the visual input signal provided by the active retinal cells informing you that the cat is not actually there. Following visual pathway damage, a CBS patient’s brain ‘fills in’ the missing visual information in the world around them, drawing on memory and experience present in the higher visual centres. The inhibition normally provided by visual input on higher brain centres is lost and thus what would usually be ‘imagined’ is instead perceived as being ‘seen’.

Though this remains one of multiple theories at present, there is evidence to support it. In a study by Merabet and colleagues10, healthy individuals were fitted with blindfolds and monitored over five days. The sudden and complete visual deprivation induced visual hallucinations akin to those seen in CBS, in over ~70% of subjects. A similar phenomenon is also seen in phantom limb pain11, a syndrome in which recent amputees complain of pain in the amputated, missing limb. It is theorised here too, that the loss of sensory input produces hallucinatory sensation. However, the hallucinations are tactile, corresponding to the sensory domain lost in this case.

Interestingly, external social factors may also play a role in CBS pathogenesis. Jones and colleagues12 saw that CBS patients experienced an exacerbation of visual hallucinations during the recent COVID-19 pandemic and that this was linked significantly to increased social isolation and loneliness. It has been suggested that this social isolation contributes in some form to the sensory deprivation that triggers visions7.

The picture thus remains incomplete and the answer to the question: “What causes these people to hallucinate?” remains elusive. Due to our poor understanding of the pathophysiology of this syndrome, we lack effective therapies for managing it. Improving a patient’s vision with methods such as eyeglasses or laser eye surgery has been reported to alleviate the incidence of hallucinations13. However, where interventions to enhance remaining vision are unsuccessful, the only remaining route of treatment is pharmacological. Unfortunately this is largely inefficacious and can often elicit unwanted side effects13. In the meantime, patients like Eric continue to face deterioration of their condition.

Further research into this intriguing syndrome is urgently needed in order to develop better therapeutics. In this process, we may also move one step closer to understanding the mystery that is the human mind.

Word Count: 1000

Bibliography

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   2. Pang L. Hallucinations Experienced by Visually Impaired: Charles Bonnet Syndrome. Optom Vis Sci. 2016 Dec;93(12):1466–78.
   3. Damas-Mora J, Skelton-Robinson M, Jenner FA. The Charles Bonnet Syndrome in perspective. Psychol Med. 1982 May;12(2):251–61.
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   6. Subhi Y, Nielsen MA, Scott DAR, Holm LM, Singh A. Prevalence of Charles Bonnet syndrome in low vision: a systematic review and meta-analysis. Ann Eye Sci. 2022 Jun 15;7(0):12–12.
   7. Jones L, Ditzel-Finn L, Enoch J, Moosajee M. An overview of psychological and social factors in Charles Bonnet syndrome. Ther Adv Ophthalmol. 2021 Jan 1;13:25158414211034716.
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   9. Ramachandran VS, Blakeslee S. Phantoms in the Brain: Human Nature and the Architecture of the Mind. Fourth Estate; 1999. 328 p.
   10. Merabet LB, Maguire D, Warde A, Alterescu K, Stickgold R, Pascual-Leone A. Visual Hallucinations During Prolonged Blindfolding in Sighted Subjects. J Neuroophthalmol. 2004 Jun;24(2):109.
   11. Guenther K. ‘It’s All Done With Mirrors’: V.S. Ramachandran and the Material Culture of Phantom Limb Research. Med Hist. 2016 Jul;60(3):342–58.
   12. Jones L, Ditzel-Finn L, Potts J, Moosajee M. Exacerbation of visual hallucinations in Charles Bonnet syndrome due to the social implications of COVID-19. BMJ Open Ophthalmol. 2021 Feb 1;6(1):e000670.
   13. Hartney KE, Catalano G, Catalano MC. Charles Bonnet Syndrome: Are Medications Necessary? J Psychiatr Pract. 2011 Mar;17(2):137.

Bonnet was inspired by the natural world, performing experiments on both insects and plants in his early life. His observations of plant physiology are documented in the 1754 publication, Recherches sur l’usage des feuilles dans les plantes (“Research in the Usage of Leaves of Plants”)4. In this work, he described a phenomenon which he has since been credited as the first to discover—epinasty in the growth of leaves5,6. He observed that, in response to changes in the environment such as light, the upper side of a leaf would bend downwards while the lower side bent upwards. This occurs as a result of preferential elongation of cells on the upper surface—overpowering, almost, the cells on the lower surface. This botanical phenomenon brings to mind the mechanism of CBS, in which the brain takes over the eyes in perceiving images in response to environmental input. Whilst Bonnet may not have drawn such a distinct connection, perhaps it was his eye for the plasticity and interaction between components of living systems that helped him recognise his grandfather’s vision impairment and hallucination as two parts of the same picture. Neuroimaging studies have since supported the idea that a loss of afferent visual sensory input results in disinhibition and spontaneous firing of vision-associated regions in the brain7,8.

There can be a tendency, often for logistical reasons, to categorise medical conditions under the umbrellas of specialties and view their management as the responsibility of one specialist or another, but such a convenient delineation rarely exists in the pathophysiology of disease. Much like how Bonnet studied different facets of natural life, research and collaboration from different angles may help us to further understand CBS, its risk factors and its treatment.

As his eyesight deteriorated, Bonnet shifted his work from observational biology to theory and philosophy. Instead of presenting the outcomes of observation and experiment, he considered existing evidence concerning the natural world and formulated conjectures. He published some of these in 1769 in La palingénésie philosophique (“The Philosophical Revival”), which documents theories on reproduction and evolution9. In response to new fossil evidence of extinct species, Bonnet presented the theory that living organisms progressively improved through acquiring traits that would help them to survive catastrophic events on Earth. Although this did not precisely match Charles Darwin’s theory, Bonnet’s development of new hypotheses contributed to our understanding of evolution as it is today.

For doctors, it is this same readiness to consider what may lie slightly beyond our understanding that prepares us to help patients with an unexpected presentation. Awareness of CBS is variable, with one survey of general practitioners revealing that 54.7% of respondents were unaware of the condition10. When patients present with hallucinations, a psychiatric aetiology is often assumed and a misdiagnosis of psychosis, delirium or dementia can be made11. To avoid inflicting patients with the distress of being misdiagnosed and incorrectly treated, we must be willing to honour their account of their own experience, like Bonnet considering paleontological evidence, and explore what may underlie their presentation with an open mind. Bonnet demonstrates through his philosophical pursuits how we can approach patients experiencing symptoms that do not align with familiar diagnoses—and face our own gaps in clinical knowledge.

In the 18th century, scholars in the field of psychology had posited that knowledge and understanding were based on innate ideas and reasoning, rather than on sensory experience. Bonnet, informed by his study of biology, philosophy and no less his personal experience, suggested that there was more fluidity to the psyche. He highlighted in Essai analytique sur les facultés de l’âme and his earlier work Essai de psychologie (“Essay on Psychology”) that consciousness was not a passive product of innate ideas, but an essential feature of the mind that allowed individuals to actively reflect, and was shaped by one’s environment and experiences1,12. What he had not yet discovered at the time was that this principle could also be applied to CBS.

More modern research has suggested that amongst patients experiencing deteriorating vision, those who are aware of the possibility of CBS before its onset may arrive at better outcomes compared to those who are not13. Whilst the psychological and environmental phenomena driving people’s varying experiences of CBS continue to be elucidated, Bonnet had in his time pinpointed the importance of mental processes in a condition apparently concerning vision. Perhaps his insight into the powers of the mind helped him to confront his own declining eyesight that eventually threatened to hinder his life and academic career.

Charles Bonnet was not only an observer of his eponymous syndrome, but a scientist whom medical professionals may be able to appreciate as more than a name in the textbook. While the full breadth of his work is beyond the scope of this essay, we can learn from his careful consideration of the complexity of physiology, his receptivity to new information and ideas, and not least his contemplation on the influence of psychology on perception. These can equip us to sensitively approach CBS, and indeed other medical conditions. Illness is rarely of a physical nature alone—it is up to us to recognise the unseen component and pay attention to it in our therapeutic approach.

References

1. Bonnet C. Essai analytique sur les facultés de l’âme. 1760 https://gallica.bnf.fr/ark:/12148/bpt6k1040584p (accessed 22 Apr 2023).
2. de Morsier G. Le syndrome de Charles Bonnet: hallucinations visuelles des vieillards sans déficience mentale. Ann Med Psychol (Paris) 1967; 2: 678–702.
3. Hedges TR. Charles Bonnet, his life, and his syndrome. Surv Ophthalmol 2007; 52. doi:10.1016/j.survophthal.2006.10.007.
4. Bonnet C. Recherches sur l’usage des feuilles dans les plantes. 1754 https://gallica.bnf.fr/ark:/12148/bpt6k15204009 (accessed 23 Apr 2023).
5. Yin HC. Diaphototropic Movement of the Leaves of Malva Neglecta. Am J Bot 1938; 25: 1–6.
6. Cera R. Lawrence. Charles Bonnet (1720-1793). Embryo Proj. Encycl. 2018. https://embryo.asu.edu/pages/charles-bonnet-1720-1793 (accessed 22 Apr 2023).
7. Vaphiades MS, Celesia GG, Brigell MG. Positive spontaneous visual phenomena limited to the hemianopic field in lesions of central visual pathways. Neurology 1996; 47: 408–417.
8. Adachi N, Watanabe T, Matsuda H, Onuma T. Hyperperfusion in the lateral temporal cortex, the striatum and the thalamus during complex visual hallucinations: single photon emission computed tomography findings in patients with Charles Bonnet syndrome. Psychiatry Clin Neurosci 2000; 54: 157–162.
9. Bonnet C. La palingénésie philosophique. 1770 https://gallica.bnf.fr/ark:/12148/bpt6k75331q (accessed 22 Apr 2023).
10. Gordon KD, Felfeli T. Family physician awareness of Charles Bonnet syndrome. Fam Pract 2018; 35: 595–598.
11. Jan T, del Castillo J. Visual Hallucinations: Charles Bonnet Syndrome. West J Emerg Med 2012; 13: 544–547.
12. Bonnet C. Essai de psychologie. 1755 https://gallica.bnf.fr/ark:/12148/bpt6k64847461 (accessed 23 Apr 2023).
13. Cox TM, ffytche DH. Negative outcome Charles Bonnet Syndrome. Br J Ophthalmol 2014; 98: 1236–1239.