Sebastian Yim

Visual hallucinations, in the absence of psychopathology, remains a challenge for diagnosis in clinicians. Charles Bonnet Syndrome (CBS) is a condition whereby a patient experiences visual hallucinations, with clear insight into their nature; this often occurs in people with varying degrees of vision loss (1). While acknowledging that these phenomena are illusory, they may still cause significant distress to the patient. As a result, prompt awareness and understanding of the condition is essential. However, CBS remains difficult to diagnose through a lack of an accepted set of criteria (2); this article will briefly address the concept of visual acuity in its diagnosis, alongside some future recommendations to clinicians.

Although no set diagnostic criteria exist, there are many overlapping features that CBS patients exhibit: these include prominent visual hallucinations, preserved insight, and a lack of additional psychopathology which better explains the presentation (1). Interestingly, one criterion commonly expressed is that many patients have some degree of loss in visual acuity (2). One study showed a 12% prevalence in patients with visual acuity showcasing criteria resembling CBS (3).

However, to date, there has been no definitive consensus over the scientific basis for visual hallucinations in CBS. The current understanding revolves around de-afferentation of sensory signals, resulting in the disinhibition of neural networks along the visual pathway (4). The brain adapts by lowering the threshold for activation; its spontaneous firing is what causes the increased electrical activity, thereby manifesting as visual phenomena. This theory has been demonstrated through empirical evidence, showcasing a loss of inhibitory tone (2) and cortical hyperexcitability in CBS patients (5), and even replicated through visual deprivation experiments (6). Together, this points to the idea that visual acuity is a central tenet to the diagnosis of CBS.

However, the overall evidence remains unconvincing. Since loss in visual acuity is correlated to visual phenomena, several case studies (7) have shown that those phenomena are no longer be present once the visual acuity is corrected, for instance through surgery. Despite this, studies have shown a prevalence of CBS in patients with preserved visual acuity. A cross-sectional report (8) on the epidemiology of CBS in Asia found not only a lower prevalence compared to European surveys, but that CBS symptoms occurred in good visual acuity. This was corroborated with another case report (9) of 4 patients, challenging whether the idea that the degree of visual acuity is a pre-requisite for CBS. Importantly, this initially seems to contradict the de-afferentation theory as well – if visual pathways are still intact, it becomes unclear how this leads to hallucinations.

However, recent neuroimaging breakthroughs have showed the importance of functional connectivity: an expression of how the neural networks function with one another. If the synapses and neurons are the ‘hardware’ within our brain, how they all operate together is the ‘software’. During hallucinations, CBS patients show increased connectivity with other areas, such as the cerebellum (10), with heightened activity in networks never thought to play a role in visual processing (11). Importantly, even if pathways are structurally connected, its temporal relationship is key to show any dysfunction. There is still a paucity of studies which probe into the risk factors or causes of altered functional connectivity within CBS patients. Regardless, it showcases the importance of not only intact neural networks but its correct functioning when describing visual neurobiology.

One reason for the discrepancies is a lack of studies and its under-representation. Much of the evidence around CBS remains either cross-sectional or anecdotal in nature – to date, there has not been a systematic review outlining any significant estimates, especially regarding its prevalence – currently an enormous range from 0.4% to 63% (3,6,8). Secondly, CBS encompasses different sub-specialties: ophthalmology, neurology, psychiatry, and geriatric medicine. Therefore, CBS is tackled from different angles, which rarely offer complementary viewpoints: for the ophthalmologist, is CBS the eye disease itself, or the loss of acuity which is to be corrected (9)? For the neurologist, can CBS be treated as distinct from any age-related neurological impairment? Age is likely a significant confounder, one that has yet to be truly disentangled.

An overlap exists with dementia and visual hallucinations being an early sign (12); combined with the incidence of age-related eye diseases, it becomes increasingly difficult to determine the causal nature CBS might play in these conditions. Lastly, there remains a reluctance of the patient to disclose the information: if patients still believe hallucinations must solely occur in the context of psychiatric illness, these symptoms are likely less voiced. Interestingly, de Morsier, the clinician who gave its eponymous name, argued he never meant to conflate CBS with eye disease (1) – regardless, it remains a significant relationship at play.

Therefore, it seems pertinent to describe any future directions from the viewpoints of the academic and clinician. From the academic perspective, more studies are needed, particularly from the angle of visual acuity and its relationship to visual phenomena. Moreover, further research into the nature of these visual hallucinations is required. If the de-afferentation theory holds true, this should be correlated with the type of visual hallucinations, through functional imaging or connectivity studies. From the clinician’s perspective, it is important to communicate with patients and their families now. It is important to try and educate groups over any potential distress these hallucinations may bring, and provide available options for symptomatic benefit. Ultimately, inter-professional collaborations may be needed, attempting to definitively propose a set of criteria all areas agree upon to move diagnosis and effective treatment forward.

Overall, CBS remains an under-diagnosed condition, with its complexity in pathogenesis its main downfall. While further studies may one day elucidate and map visual hallucinations onto the affected regions of visual cortex, a key step involves how this may translate into patient care. Prompt recognition, clinician education, and management of additional co-morbidities all aim to provide patient empowerment. For an increasingly ageing population, the awareness of CBS remains as paramount as ever.

References

1. Ffytche DH. Visual hallucinations and the Charles Bonnet syndrome. Current psychiatry reports. 2005 May;7(3):168-79.
2. Plummer C, Kleinitz A, Vroomen P, Watts R. Of Roman chariots and goats in overcoats: the syndrome of Charles Bonnet. Journal of clinical neuroscience. 2007 Aug 1;14(8):709-14.
3. Teunisse RJ, Cruysberg JR, Verbeek A, Zitman FG. The Charles Bonnet syndrome: a large prospective study in The Netherlands: A study of the prevalence of the Charles Bonnet syndrome and associated factors in 500 patients attending the University Department of Ophthalmology at Nijmegen. The British Journal of Psychiatry. 1995 Feb;166(2):254-7.
4. Marschall TM, Brederoo SG, Curcic-Blake B, Sommer IE. Deafferentation as a cause of hallucinations. Current opinion in psychiatry. 2020 May 1;33(3):206-11.
5. Painter DR, Dwyer MF, Kamke MR, Mattingley JB. Stimulus-driven cortical hyperexcitability in individuals with Charles Bonnet hallucinations. Current Biology. 2018 Nov 5;28(21):3475-80.
6. Jan T, Del Castillo J. Visual hallucinations: Charles bonnet syndrome. Western journal of emergency medicine. 2012 Dec;13(6):544.
7. Smith CS, Nichols J, Riaz KM. Remission of Charles Bonnet syndrome after cataract extraction. Canadian Journal of Ophthalmology. 2018 Dec 1;53(6):e221-2.
8. Tan CS, Lim VS, Ho DY, Yeo E, Ng BY, Eong KA. Charles Bonnet syndrome in Asian patients in a tertiary ophthalmic centre. British Journal of Ophthalmology. 2004 Oct 1;88(10):1325-9.
9. Madill SA, Ffytche DH. Charles Bonnet syndrome in patients with glaucoma and good acuity. British Journal of Ophthalmology. 2005 Jun 1;89(6):785-6.
10. Martial C, Larroque SK, Cavaliere C, Wannez S, Annen J, Kupers R, Laureys S, Di Perri C. Resting-state functional connectivity and cortical thickness characterization of a patient with Charles Bonnet syndrome. PLoS One. 2019 Jul 18;14(7):e0219656.
11. Piarulli A, Annen J, Kupers R, Laureys S, Martial C. High-density EEG in a Charles Bonnet syndrome patient during and without visual hallucinations: a case-report study. Cells. 2021 Aug 5;10(8):1991.
12. Mosimann UP, Rowan EN, Partington CE, Collerton D, Littlewood E, O’Brien JT, Burn DJ, McKeith IG. Characteristics of visual hallucinations in Parkinson disease dementia and dementia with Lewy bodies. The American Journal of Geriatric Psychiatry. 2006 Feb 1;14(2):153-60.