Charles Bonnet syndrome in patients with Stargardt disease: prevalence and risk factors.

AIMS: To describe the prevalence of the Charles Bonnet syndrome (CBS) and search for potential CBS risk factors in a Dutch Stargardt disease (STGD1) cohort. METHODS: Eighty-three patients with STGD1 were screened for CBS. They underwent a full eye examination. All patients completed the social functioning domain of the 36-Item Short Form Health Survey questionnaire. Participants suspected of CBS were interviewed to further evaluate their visual hallucinations. RESULTS: CBS prevalence was 8.4%. Six out of seven patients with CBS were women. CBS was not associated with age (p=0.279, Mann-Whitney). Patients with CBS had a significant lower social functioning score (p<0.05, Mann-Whitney). All seven patients with CBS were in the category of vision impairment (visual acuity <6/12, but ≥3/60). Moreover, first hallucinations manifested after a drop in visual acuity. The retinal atrophic area of the worst eye tended to be lower in the CBS group (range 0.11-9.86 mm2) as compared with controls (range 0-180 mm2). There was no relation between the position of the scotoma and the location of the visual hallucinations. CONCLUSION: The relative high CBS prevalence in STGD1 suggests that CBS may be more prevalent in younger ophthalmic patients than currently presumed. In this specific group of patients, we established social isolation and acquired vision impairment as risk factors for CBS. There was a female preponderance among patients with CBS. Age and retinal pigment epithelium atrophy were not identified as significant risk factors. We should actively diagnose CBS in patients of any age who fulfil the criteria for the category vision impairment, especially in cases where social isolation is suspected.

Charles Bonnet Syndrome Associated With Recurrent Hypertensive Crisis.

Charles Bonnet syndrome (CBS) is a disorder of visual hallucinations in psychologically normal patients with ocular disease or damage to visual pathways. The etiology of CBS is not fully understood. It is associated with various triggers, with age-related macular degeneration the most common; other triggers are systemic diseases such as stroke, multiple sclerosis, and anemia as well as lighting issues, fatigue, and medical or surgical eye treatments. Visual disturbances such as decreased visual acuity, visual field deficits, or visual hallucinations are common in association with hypertensive encephalopathy. We describe a patient with episodic CBS triggered by recurrent hypertensive crises, which resolved with blood pressure management in the hospital setting.

Transcranial Direct Current Stimulation in the Treatment of Visual Hallucinations in Charles Bonnet Syndrome: A Randomized Placebo-Controlled Crossover Trial.

OBJECTIVE: To investigate the potential therapeutic benefits and tolerability of inhibitory transcranial direct current stimulation (tDCS) on the remediation of visual hallucinations in Charles Bonnet syndrome (CBS). DESIGN: Randomized, double-masked, placebo-controlled crossover trial. PARTICIPANTS: Sixteen individuals diagnosed with CBS secondary to visual impairment caused by eye disease experiencing recurrent visual hallucinations. INTERVENTION: All participants received 4 consecutive days of active and placebo cathodal stimulation (current density: 0.29 mA/cm2) to the visual cortex (Oz) over 2 defined treatment weeks, separated by a 4-week washout period. MAIN OUTCOME MEASURES: Ratings of visual hallucination frequency and duration following active and placebo stimulation, accounting for treatment order, using a 2 × 2 repeated-measures model. Secondary outcomes included impact ratings of visual hallucinations and electrophysiological measures. RESULTS: When compared with placebo treatment, active inhibitory stimulation of visual cortex resulted in a significant reduction in the frequency of visual hallucinations measured by the North East Visual Hallucinations Interview, with a moderate-to-large effect size. Impact measures of visual hallucinations improved in both placebo and active conditions, suggesting support and education for CBS may have therapeutic benefits. Participants who demonstrated greater occipital excitability on electroencephalography assessment at the start of treatment were more likely to report a positive treatment response. Stimulation was found to be tolerable in all participants, with no significant adverse effects reported, including no deterioration in preexisting visual impairment. CONCLUSIONS: Findings indicate that inhibitory tDCS of visual cortex may reduce the frequency of visual hallucinations in people with CBS, particularly individuals who demonstrate greater occipital excitability prior to stimulation. tDCS may offer a feasible intervention option for CBS with no significant side effects, warranting larger-scale clinical trials to further characterize its efficacy.

Investigation of structural brain changes in Charles Bonnet Syndrome.

BACKGROUND AND OBJECTIVES: In Charles Bonnet Syndrome (CBS), visual hallucinations (VH) are experienced by people with sight loss due to eye disease or lesional damage to early visual pathways. The aim of this cross-sectional study was to investigate structural brain changes using magnetic resonance imaging (MRI) in CBS. METHODS: Sixteen CBS patients, 17 with eye disease but no VH, and 19 normally sighted people took part. Participants were imaged on a 3T scanner, with 1 mm resolution T1 weighted structural imaging, and diffusion tensor imaging with 64 diffusion directions. RESULTS: The three groups were well matched for age, sex and cognitive scores (MMSE). The two eye disease groups were matched on visual acuity. Compared to the sighted controls, we found reduced grey matter in the occipital cortex in both eye disease groups. We also found reductions of fractional anisotropy and increased diffusivity in widespread areas, including occipital tracts, the corpus callosum, and the anterior thalamic radiation. We did not find any significant differences between the eye disease participants with VH versus without VH, but did observe a negative association between hippocampal volume and VH severity in the CBS group. DISCUSSION: Our findings suggest that although there are cortical and subcortical effects associated with sight loss, structural changes do not explain the occurrence of VHs. CBS may relate instead to connectivity or excitability changes in brain networks linked to vision.

Charles Bonnet Syndrome in Patients with Open-Angle Glaucoma: Prevalence and Correlation to Visual Field Loss.

PURPOSE: To determine the prevalence and characteristics of Charles Bonnet Syndrome (CBS) and its relation to visual field loss (VFL) in patients with open-angle glaucoma (OAG). DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Adult patients (n = 337) with manifest OAG with verified VFL and without significant macular disease or extraocular conditions known to cause visual hallucinations. METHODS: Patients attending the glaucoma outpatient department of the Skåne University hospital, Malmö, Sweden, between April 1, 2018, and December 31, 2018, were consecutively evaluated for inclusion. Potentially eligible patients admitting to having complex visual hallucinations were interviewed to explore the characteristics of their hallucinatory experiences. Recent automated visual field examinations were available for all participants, and swept-source OCT was performed in participants with CBS to rule out previously undiagnosed macular pathology. The correlation between potential risk factors and CBS was evaluated with logistic regression analysis. MAIN OUTCOME MEASURE: Prevalence of CBS in patients with OAG. RESULTS: Charles Bonnet Syndrome was found in 7.1% (95% confidence interval [CI], 4.7-10.6) of patients with OAG. Participants with CBS were more likely to have at least 1 eye with a visual field index (VFI) of ≤30% compared with those without CBS (71% vs. 34.2%; P = 0.001). Although the best-corrected visual acuity (BCVA) in the worse eye was significantly lower in participants with CBS (decimal equivalent of Snellen BCVA: 0.25 vs. 0.6, P = 0.003), 33% of these participants had a BCVA of ≥0.5 in the worse eye. In multivariable analysis, CBS was correlated to the VFI of the better eye (odds ratio, 0.984; 95% CI, 0.969-0.998, P = 0.030) and the BCVA of the worse-seeing eye (odds ratio, 0.210; 95% CI, 0.046-0.952, P = 0.043). CONCLUSIONS: Charles Bonnet Syndrome was not a rare condition in patients with glaucoma. Patients with a combination of advanced VFL and low BCVA had the highest risk of CBS; however, 1 of 3 patients with CBS had a BCVA of ≥0.5 in both eyes. These findings emphasize the importance of being attentive to symptoms of CBS in patients with glaucomatous VFL even when visual acuity is preserved.

Atypical Charles Bonnet syndrome secondary to frontal meningioma: a case report.

BACKGROUND: Charles Bonnet Syndrome (CBS) is a rare clinical entity that is classically composed of visual hallucinations in the context of an altered optic pathway with preservation of reality judgment. This case aims to present the association of visual hallucinations with complex alterations of the nervous structures adjacent to the visual pathway and an atypical clinical presentation, thus explaining the possible mechanisms involved in the generation of these symptoms. CASE PRESENTATION: A 43-year-old man presents seeking care due to visual hallucinations with partial preservation of reality judgment and symptoms compatible with a major depressive disorder, including irritability and diminished hygiene habits. He has a history of complete gradual loss of vision and hyposmia. Due to poor treatment response during hospitalization, an MRI was obtained, which showed a frontal tumor lesion with meningioma characteristics adjacent to the olfactory groove and compression of the optic chiasm. He underwent surgical resection of the lesion, which remitted the psychotic symptoms, but preserving the visual limitation and depressive symptoms. CONCLUSIONS: The presence of visual hallucinations, without other psychotic features as delusions, is a focus of attention for basic structural pathologies in the central nervous system. Affection at any level of the visual pathway can cause CBS. When finding atypical symptoms, a more in-depth evaluation should be made to allow optimization of the diagnosis and treatment.

How do the blind 'see'? The role of spontaneous brain activity in self-generated perception.

Spontaneous activity of the human brain has been well documented, but little is known about the functional role of this ubiquitous neural phenomenon. It has previously been hypothesized that spontaneous brain activity underlies unprompted (internally generated) behaviour. We tested whether spontaneous brain activity might underlie internally-generated vision by studying the cortical visual system of five blind/visually-impaired individuals who experience vivid visual hallucinations (Charles Bonnet syndrome). Neural populations in the visual system of these individuals are deprived of external input, which may lead to their hyper-sensitization to spontaneous activity fluctuations. To test whether these spontaneous fluctuations can subserve visual hallucinations, the functional MRI brain activity of participants with Charles Bonnet syndrome obtained while they reported their hallucinations (spontaneous internally-generated vision) was compared to the: (i) brain activity evoked by veridical vision (externally-triggered vision) in sighted controls who were presented with a visual simulation of the hallucinatory streams; and (ii) brain activity of non-hallucinating blind controls during visual imagery (cued internally-generated vision). All conditions showed activity spanning large portions of the visual system. However, only the hallucination condition in the Charles Bonnet syndrome participants demonstrated unique temporal dynamics, characterized by a slow build-up of neural activity prior to the reported onset of hallucinations. This build-up was most pronounced in early visual cortex and then decayed along the visual hierarchy. These results suggest that, in the absence of external visual input, a build-up of spontaneous fluctuations in early visual cortex may activate the visual hierarchy, thereby triggering the experience of vision.

Three cases of Charles Bonnet Syndrome in patients with advanced glaucomatous visual field loss but preserved visual acuity.

PURPOSE: To describe three cases of Charles Bonnet syndrome (CBS) in glaucoma patients with preserved visual acuity. METHODS: Three glaucoma patients who had taken part in a recent CBS study were interviewed about their hallucinations. The patients underwent macular optical coherence tomography (OCT) of both eyes. The visual function was evaluated with visual field measurement (Humphrey visual field analyser) and visual acuity testing (Snellen scale). RESULTS: All three patients had preserved visual acuity (≥0.5 in both eyes) and at least one eye with advanced visual field defect (Mean Deviation worse than -12.00 decibel). They all reported vivid visual hallucinations with insight into the unreal nature of the hallucinations. CONCLUSION: Charles Bonnet syndrome can occur in glaucoma despite preserved visual acuity. Awareness of this relation is desirable among clinicians, as it will improve communication with patients.

Visual hallucinations and sight loss in children and young adults: a retrospective case series of Charles Bonnet syndrome.

BACKGROUND/AIMS: Charles Bonnet syndrome (CBS) is a complication of sight loss affecting all ages; yet, few childhood cases have been reported. Our aim is to raise awareness of this under-reported association occurring in children and young adults in order to prevent psychological harm in this age group. METHODS: A retrospective case series reviewing medical notes of patients <25 years of age with sight loss and reported CBS at a single centre hospital eye service in London, United Kingdom. Search of electronic patient records identified 13 patients experiencing hallucinatory events over a 9-year period. Outcomes were patient demographics including ocular diagnosis, visual acuity at time of onset, characteristics of hallucinations, clinical management strategies and patient-reported affliction. RESULTS: Eight patients were diagnosed with progressive inherited retinal diseases, primarily Stargardt disease (N=5). Clinical history indicated patients had significantly reduced best-corrected visual acuity (BCVA) in at least one eye at onset; median (IQR) worse eye BCVA was 1.0 (0.86-1.6) logarithm of minimum angle of resolution(LogMAR). CBS significantly affected patients' personal lives including education, diet and sleep. Clinical management was varied, mostly relating to reassurance at the point of contact. CONCLUSION: We describe the clinical features of young patients with CBS, with management strategies and aspects of negative outcomes. High potential caseload and risk of psychological harm merit further research. Increased awareness among healthcare professionals and patient education to forewarn susceptible individuals may reduce the overall impact and improve coping with symptoms.

Clinical Characteristics of the Charles Bonnet Syndrome in Patients with Neovascular Age-Related Macular Degeneration: The Importance of Early Detection.

PURPOSE: We investigated the characteristics, prognosis, and clinical outcome of the Charles Bonnet syndrome (CBS) in patients with neovascular age-related macular degeneration (AMD). METHODS: Five hundred psychiatrically healthy patients with neovascular AMD were screened for CBS. The individuals that fulfilled the inclusion criteria were systematically interviewed using a structured questionnaire that covered the impact, prognosis, risk factors, phenomenology, symptoms, and knowledge about the syndrome. A control group of 45 patients was used for comparison. Demographic data, current medication, and ocular risk factors were collected in all patients. RESULTS: Forty-five patients with CBS were identified. The majority of patients reported images that consisted of colored (62%) animals (44%) or faces (42%) that lasted for seconds (53%). Most patients reported a self-limited disease with a median duration of symptoms between 9 and 11.5 months, with only 7% knowing about CBS at symptom onset. The degree of visual deficit did not predict the characteristics, complexity, frequency, duration, or impact of visual hallucinations. One-third of patients reported negative outcome, which was associated with shorter duration of CBS (p = 0.023), fear-inducing images (p < 0.001), and impact on daily activities (p = 0.015). CONCLUSION: The prevalence of CBS in neovascular AMD patients is high and clinically relevant. Patients with recent onset of visual hallucinations and describing fear-inducing images are at greater risk for negative outcome. Periodic screening may minimize the negative consequences of this disease.

Screening for Charles Bonnet syndrome: Should the definition be reconsidered?

Purpose: Charles Bonnet syndrome (CBS) is a condition in which individuals with visual impairment (VI) and with no cognitive deficits experience visual hallucinations, typically with no other sensory hallucinations. Although few isolated case reports of CBS from India have been published, the prevalence for CBS in India is largely unknown. The primary aim of this study was to estimate CBS prevalence in patients with vision impairment visiting a tertiary eye care center. Methods: The study was conducted in two phases. In phase 1, patients with VI, age ≥40 years with presenting visual acuity worse than 20/63 were enrolled. In phase 2, patients with presenting visual acuity worse than 20/63 and/or with binocular visual field loss, age ≥18 years were recruited. A CBS survey was administered only to those who passed a screening test for cognition impairment. Results: A total of 218 patients were screened (phase 1 = 113 and phase 2 = 105). Two-hundred ten patients (mean age ± standard deviation = 49.2 ± 17.3 years, males = 139) were found eligible to complete the CBS survey. Fourteen patients were found to have visual hallucinations. In addition, three other patients had visual hallucinations with associated auditory input to the visual imagery. All patients had complete insight about their hallucinations. Conclusion: Depending on the inclusion criteria, we found the prevalence for CBS in patients with VI to vary between 6.7% to 8.1% (if including patients with auditory input). More investigation is needed to assess the associated role of other sensory inputs (e.g. auditory) with the visual imagery experienced in CBS.