Charles Bonnet Syndrome

Etiology

Except for congenital blindness, CBS can originate from any factor affecting the visual pathway, extending from the visual cortex down to the eyes.[21]

Common etiologies include:

• Diabetic retinopathy
• Age-related macular degeneration
• Cerebral infarctions
• Glaucoma
• Macular degeneration
• Cataract
• High myopia
• Retinitis Pigmentosa
• Optic Neuritis
• Retinal vein occlusion
• Central retinal arterial occlusion
• Occipital stroke
• Temporal arteritis

The leading etiological theory for CBS is the phantom vision theory. Similar to phantom limb pain, phantom vision is a cortical deafferentiation phenomenon leading to the perception of afferents that do not exist.[22] CBS arises from a complex interplay among visual pathway deafferentation, cortical hyperexcitability, and impaired sensory integration, typically following significant visual loss. The syndrome is characterized by vivid, formed visual hallucinations occurring in mentally intact individuals with impaired vision. While the precise mechanisms remain incompletely understood, several pathophysiological and etiological factors have been proposed.[23]

Visual Deafferentation and Cortical Release Theory

The most widely accepted explanation is the “deafferentation” or “release” hypothesis.

• When the retinal or optic input to the visual cortex is reduced or lost due to ocular or optic nerve disease, the visual association cortex becomes hyperactive in the absence of normal afferent stimulation.
• This spontaneous cortical activity leads to phantom visual perceptions, analogous to the phantom limb phenomenon after amputation.
• Studies using functional MRI and positron emission tomography imaging have demonstrated increased spontaneous activity in the occipital and temporal visual areas in patients with CBS.
• This cortical disinhibition results in the generation of internally generated visual imagery that is interpreted as real visual experiences.[24]

Ocular and Optic Pathway Causes (Peripheral Etiology)

CBS is almost always associated with significant bilateral visual impairment, and the underlying ocular conditions include:

• Age-related macular degeneration: The most common cause, due to central visual field loss
• Glaucoma: Advanced stages leading to peripheral field defects and visual isolation
• Diabetic retinopathy: Due to patchy retinal ischemia and photoreceptor loss
• Retinitis pigmentosa: Progressive photoreceptor degeneration producing sensory deprivation.
• Optic neuritis or ischemic optic neuropathy: Damage to optic nerve fibers leading to central vision loss
• Cataract and corneal opacities: Transient visual deprivation can (but rarely) trigger CBS after surgery (post-cataract CBS)
• Retinal detachment or central retinal artery occlusion: Sudden severe visual loss leading to abrupt cortical deprivation [1]

Thus, CBS most commonly develops when visual acuity deteriorates below 6/18 or when severe field constriction occurs.

Neurophysiological Factors

In the absence of external input, the visual cortex neurons enter a state of spontaneous firing and synaptic reorganization:

• The primary visual cortex (V1) and extrastriate visual association areas (V2–V5) exhibit aberrant excitation, leading to perception of vivid imagery.
• Neurochemical imbalance, including reduced inhibitory gamma-aminobutyric acid (GABA)ergic activity and excess glutamatergic signaling, contributes to this hyperexcitability.
• Some evidence also implicates abnormal serotonergic activity, particularly in the visual cortex and brainstem visual pathways, which may explain CBS's partial responsiveness to selective serotonin reuptake inhibitors in some cases.[18]

Central Processing and Cognitive Mechanisms

CBS requires preserved cognitive function, distinguishing it from psychotic hallucinations.

• The frontal and parietal cortical networks responsible for reality testing and insight remain intact.
• Thus, while patients perceive vivid images, they usually recognize these as unreal.
• Functional imaging studies suggest that CBS results from hyperactivation of visual association areas (eg, the fusiform gyrus for faces, the lingual gyrus for patterns) without prefrontal involvement, which accounts for the absence of delusional interpretation.[20]

Risk Factors and Predisposing Conditions

Several factors increase the likelihood of CBS:

• Advanced age (>65 years): This is due to the higher prevalence of ocular diseases and cortical plasticity changes.
• Sudden or progressive vision loss: This can lead to cortical disinhibition.
• Sensory deprivation: Dark environments or prolonged visual inactivity enhance hallucination frequency.
• Social isolation and psychological stress may exacerbate cortical overactivity.
• Neurodegenerative diseases such as Alzheimer or Parkinson disease, when accompanied by ocular pathology, may predispose individuals to CBS.[2]

The “Perceptual Release” Model

An extension of the deafferentation theory, this model proposes that:

• Normally, bottom-up sensory input suppresses spontaneous activity in visual memory circuits.
• In CBS, loss of retinal input “releases” these stored percepts from memory, resulting in externally projected visual imagery.
• The content of hallucinations often reflects stored visual memories (faces, landscapes, animals), supporting this theory.[13]

Transient or Iatrogenic Etiologies

CBS can occasionally appear after:

• Ocular surgery (eg, cataract or retinal procedures) due to sudden changes in light stimulation or neural adaptation.
• Prolonged occlusion therapy or eye patching causes temporary visual deprivation.
• Reversible ischemia or optic neuritis episodes, after which hallucinations may subside as visual input returns (see Table 1).[25]

 Table 1. Etiological Factors in Charles Bonnet Syndrome

ARMD, age-related macular degeneration; GABA, gamma-aminobutyric acid

In essence, CBS arises from visual sensory deprivation, which leads to cortical hyperactivity in a neurologically intact individual. The loss of afferent input “releases” intrinsic visual imagery, resulting in complex hallucinations without psychiatric disease. Recognition of the underlying etiologies—particularly ocular and optic nerve disorders—is essential for accurate diagnosis and patient reassurance.[15]

Epidemiology

CBS is an underrecognized but relatively common condition among individuals with moderate to severe visual impairment, particularly in older adults. The reported prevalence varies widely, reflecting differences in diagnostic awareness, patient reporting, and criteria used across studies.

Global Prevalence

• The global prevalence of CBS among visually impaired individuals ranges from 10% to 30%, depending on population and methodology.
• Results from a 2023 meta-analysis by Subhi et al reported a pooled prevalence of approximately 19.7% among visually impaired individuals worldwide, with higher rates in tertiary ophthalmology centers than in community settings.
• In populations with age-related macular degeneration (the leading cause of CBS), the prevalence is 15% to 30%, whereas in general ophthalmology clinics, the incidence ranges from 1% to 2%.
• The incidence and prevalence of CBS are still under investigation and require further research. The prevalence of CBS in ophthalmic populations is estimated at 10.2%.[2] In this recent meta-analysis, patients with glaucoma, low visual acuity, and retinal diseases all have similar prevalence rates for CBS. Additionally, women are at a higher risk than men.[2] The prevalence of CBS correlated with severity, with patients in vision rehabilitation endorsing it most often (24.6%).
• In the context of glaucoma, another study found a prevalence of 2.8% that correlated with the severity of the glaucoma.[26] In patients with bilateral low acuity, the prevalence was 13.5%; in patients visiting visual rehab clinics, it was 20.1%. Other predictive factors for individuals with glaucoma include age, female sex, not living alone, and reduced contrast sensitivity.[27]

Prevalence in the United States

• In United States (US) cohorts, CBS is estimated to occur in approximately 1% to 2% of patients in general ophthalmology settings and in up to 20% to 30% of individuals with significant visual impairment.
• The American Academy of Ophthalmology recognizes CBS as an essential cause of visual hallucinations in older adults with visual impairment, often misdiagnosed as dementia or psychiatric illness.
• Epidemiological data from US Veterans Affairs hospitals indicate a CBS prevalence of 12% to 18% among older adults with bilateral ocular pathology.
• Data from CBS indicate a mean age of between 70 and 85 years, within the expected range during which pathological processes leading to visual impairment or vision loss typically occur.[21][28][29] However, literature has suggested that CBS is vastly under-reported, mainly due to patients' fear of being diagnosed with a psychiatric illness.[30][31] CBS has also been reported in children, having a high incidence of rapid visual loss.[32]

Age Distribution

• CBS predominantly occurs in older adults, typically those aged 65 and older, paralleling the prevalence of age-related ocular diseases.
• Rarely, cases have been documented in younger individuals following sudden bilateral vision loss, such as from optic neuritis, retinal detachment, or trauma.
• The mean age of onset is approximately 70 to 75, and prevalence increases sharply with declining best-corrected visual acuity (<6/18 or 20/60).[33]

Sex Distribution

• Most studies report no significant sex predilection for CBS.
• However, a slight female predominance (female:male ratio ~1.3:1) has been noted in several extensive cohort studies, likely reflecting the higher incidence of age-related macular degeneration and women's longevity.
• In community-based samples, both genders are equally susceptible when matched for degree of visual loss (see Table 2).[34]

Geographical Distribution

• Developed countries such as the US, United Kingdom, Japan, and Australia report higher detection rates, attributed to greater awareness and longer life expectancy.
• Underreporting remains a significant issue in developing countries, where visual hallucinations may be stigmatized or attributed to psychiatric or cultural beliefs.
• In India and Southeast Asia, limited studies show a CBS prevalence of 6% to 10% among visually impaired older adults, often post-cataract or age-related macular degeneration-related.[35]

Table 2. Associated Ocular Conditions and Risk

Risk Factors

• Severe bilateral visual impairment (acuity worse than 6/24 or 20/80)
• Sudden vision loss (eg, retinal artery occlusion)
• Advanced age (>70 years)
• Social isolation and sensory deprivation
• Low-light environments
• Post-ophthalmic surgery states (eg, cataract, retinal procedures) [36]

Trends and Awareness

• The condition remains underdiagnosed, with only 30% to 40% of affected individuals voluntarily reporting hallucinations due to fear of being labelled psychotic.
• Increased awareness among ophthalmologists and neurologists has led to improved case recognition in recent years.
• With global population aging and increasing prevalence of visual impairment, CBS is expected to rise in incidence over the next decade.[37]

Summary

• CBS affects approximately 1 in 5 patients with moderate-to-severe vision loss, particularly among older adults.
• There is no significant sex bias, though slightly higher rates are reported in women.
• The syndrome is most frequently observed in developed nations but is likely underreported in low- and middle-income countries.
• The increasing prevalence of age-related macular degeneration and diabetic eye disease globally makes CBS a critical clinical consideration in geriatric ophthalmology.[2]

Pathophysiology

The pathophysiology of CBS begins with any factor that leads to vision loss. These factors, which can affect any part of the visual pathway, commonly include cataracts, glaucoma, diabetic retinopathy, age-related macular degeneration, and cerebral infarction affecting the visual cortex.[21][28][30] The current, most widely accepted theory of the visual hallucinations observed in CBS is that visual sensory deafferentation leads to disinhibition of cortical regions involved in vision.[38][39] This disinhibition leads to spontaneous firing in vision-associated regions, resulting in hallucinations. Study results supporting this theory have shown through neuroimaging that visual cortical regions, such as the ventral occipital lobe, spontaneously fire during hallucinations in patients who met diagnostic criteria.[40] 

Furthermore, neuroimaging revealed that hallucinations correlate with the function of the involved firing cortical region. Because hallucinations are understood through a process, CBS is not seen in congenital blindness.[41] CBS arises due to deafferentation of the visual cortex, leading to spontaneous visual hallucinations in individuals with significant visual impairment but intact cognition; this is a release phenomenon—the brain compensates for reduced sensory input by generating internally derived images. The underlying mechanisms involve neurophysiological, neurochemical, and structural changes in the visual processing pathways.

Deafferentation and Cortical Hyperexcitability

• Loss of visual input: Ocular or optic pathway diseases (eg, macular degeneration, glaucoma, diabetic retinopathy, or optic neuropathy) lead to diminished afferent impulses from the retina to the visual cortex.
• Cortical disinhibition: The sudden reduction in visual stimuli causes a compensatory increase in cortical excitability in the occipital lobe, particularly in the visual association areas (Brodmann areas 18 and 19).
• Spontaneous activation: These disinhibited neurons begin firing spontaneously, producing vivid visual hallucinations that the brain interprets as authentic images.[42]

Functional Neuroimaging Evidence

• Results from functional MRI and positron emission tomography studies show increased metabolic activity in the ventral occipital lobe, fusiform gyrus, and inferior temporal cortex during hallucination episodes.
• The ventral stream ("what" pathway)—involved in object and face recognition—is often implicated in the formation of complex hallucinations (eg, people, animals, or patterns).
• Conversely, the dorsal stream ("where" pathway) may be less involved, consistent with the stationary or non-interactive nature of hallucinations.[43]

Neurochemical Mechanisms

• Dopaminergic and serotonergic imbalance:
• Dopamine excess in visual association areas can amplify perceptual processing, contributing to visual hallucinations.
• Serotonin dysregulation (especially 5-hydroxytryptamine 2A receptor activity) is also linked to hallucinatory experiences, similar to mechanisms seen in psychosis or lysergic acid diethylamide-induced visions (see Table 3).
• GABAergic inhibition: Reduced GABA-mediated inhibition in the occipital cortex may facilitate uncontrolled excitatory discharges, promoting visual imagery.[44]

Cognitive and Perceptual Theories

• Perceptual release hypothesis: When external visual input is insufficient, the brain “fills in the gaps” using previously stored visual memories. This explains why hallucinations often consist of familiar faces, scenes, or objects.
• Predictive coding model: The brain constantly predicts sensory inputs; in CBS, sensory feedback is absent, leading to an overreliance on internal predictions that manifest as hallucinations.
• Neural network instability: Loss of sensory input leads to an imbalance between bottom-up (sensory) and top-down (cognitive) processing, resulting in autonomous activation of visual circuits.[13]

Table 3. Anatomical Site, Possible Pathophysiological Event, and Clinical Correlate in CBS

Precipitating Factors

Episodes may be triggered or exacerbated by:

• Sensory deprivation (darkness, eye closure)
• Fatigue or stress
• Social isolation
• Medications (dopaminergic, anticholinergic agents)
• Neurological comorbidities (eg, occipital stroke, temporal lobe epilepsy) [16]

Differentiation from Psychiatric Hallucinations

• In CBS, insight is preserved—patients recognize the unreal nature of hallucinations.
• The limbic system (emotional processing) and frontal lobe (reality testing) remain unaffected, distinguishing CBS from psychotic disorders or delirium.[18]

Summary Model

Visual impairment → Cortical deafferentation → Disinhibition of visual association areas → Spontaneous neuronal firing → Perception of formed visual hallucinations.[5]

Histopathology

CBS is a functional neuro-ophthalmic condition rather than a structural ocular or cerebral lesion. Therefore, conventional histopathology of ocular or neural tissue does not show specific diagnostic abnormalities. However, microscopic and neuroimaging-correlated studies have identified several pathophysiological changes in the visual pathways, retina, and occipital cortex that underlie the syndrome’s manifestations. These histopathological correlates are best understood in the context of sensory deprivation-induced cortical reorganization.[2] 

1. Retinal and Optic Nerve Changes

CBS usually occurs secondary to ocular pathologies that cause partial or complete loss of afferent visual input. Histopathologically, the following features may be seen depending on the underlying disease:

• Age-related macular degeneration: Geographic atrophy of the retinal pigment epithelium (RPE), drusen deposition between the Bruch membrane and the RPE, photoreceptor degeneration, and choriocapillaris attenuation
• Glaucoma: Loss of retinal ganglion cells and thinning of the retinal nerve fiber layer with cupping of the optic disc
• Diabetic retinopathy: Capillary basement membrane thickening, microaneurysms, pericyte loss, and intraretinal microvascular abnormalities
• Retinitis pigmentosa: Loss of rods followed by cones, pigment migration into the retina, and outer nuclear layer thinning

These peripheral degenerative changes reduce sensory transmission to the visual cortex, leading to cortical deafferentation—a key substrate for CBS.[45]

2. Occipital Cortex: Cortical Deafferentation and Disinhibition

Post-mortem and neuroimaging-correlated neuropathological studies reveal that the occipital lobe (especially Brodmann areas 17, 18, and 19) exhibits:

• No gross structural abnormalities, but
• Functional hyperexcitability and aberrant synaptic activity due to loss of inhibitory GABAergic control.
• Microscopically, there may be:
  • Increased dendritic sprouting and synaptogenesis in the visual association cortex due to chronic sensory deprivation.
  • Glial hypertrophy and mild astrocytosis, suggesting local metabolic upregulation.
  • Altered neuronal density in layers II–IV of the visual cortex, reflecting cortical remodeling.
  • Reduced synaptic pruning and increased spontaneous firing in visual neurons have been demonstrated in experimental animal models of visual deprivation.

Thus, the histopathologic correlate is not damage, but adaptive hyperplastic remodeling of cortical neurons secondary to visual input loss.[3]

3. Thalamocortical Pathways

Microscopic evaluation and tract tracing studies show:

• Atrophy or decreased myelination of fibers in the lateral geniculate nucleus (LGN) and optic radiation, secondary to chronic loss of afferent input.
• Trans-synaptic degeneration from the retina to the LGN to the visual cortex is visible.
• There is a reduction in inhibitory interneuron density in these pathways, which may facilitate unregulated excitatory discharges manifesting as hallucinations.[46]

4. Neurochemical and Cellular Alterations

While standard histopathological stains may not demonstrate these changes, biochemical and immunohistochemical analyses reveal:

• Decreased GABA receptor density in the primary visual cortex, causing loss of inhibition.
• Upregulation of N-methyl-D-aspartate receptors in the glutamatergic system contributes to cortical excitability.
• Altered serotonergic transmission, especially in the dorsal raphe nucleus and its projections to the occipital cortex, is consistent with CBS's responsiveness to selective serotonin reuptake inhibitors in some cases.
• Microglial activation and increased expression of immediate-early genes, such as c-fos and Arc, are markers of neuronal hyperactivity.[47]

5. Functional Imaging Correlates (Microscopic Analogues)

Although CBS lacks classic histological lesions, functional neuroimaging studies (functional MRI, positron emission tomography [PET], and single-photon emission computed tomography [SPECT]) provide a microscopic-level view of dynamic cortical processes, which can be conceptually related to histopathology:

• Functional MRI studies show spontaneous activation of the visual association cortices (fusiform gyrus, lingual gyrus, lateral occipital areas) during hallucination episodes.
• PET scans demonstrate increased regional glucose metabolism in the occipital and temporal visual areas.
• Electroencephalography and magnetoencephalography studies show low-frequency oscillatory discharges consistent with cortical hyperexcitability in visually deprived cortices.

These findings represent functional histopathology, highlighting the physiologic plasticity of visual neurons in the absence of afferent stimulation (see Table 4).[48]

6. Differential Neuropathologic Findings (Rule-Out Lesions)

CBS must be differentiated histologically and radiologically from structural lesions that may produce visual hallucinations:

• Occipital lobe infarcts → neuronal necrosis, gliosis, and cavitation.
• Neurodegenerative diseases (eg, Lewy body dementia, Alzheimer disease) → cortical atrophy, Lewy bodies, or neurofibrillary tangles.
• Temporal lobe epilepsy → hippocampal sclerosis and gliosis.

In contrast, CBS brains typically show preserved cortical architecture with functional, not destructive, changes.[49]

Table 4. Summary of Microscopic Findings

LGS, lateral geniculate nucleus; GABA, gamma-aminobutyric acid

Conclusion

Histopathologically, CBS does not present with destructive lesions but with adaptive and functional reorganization of the visual cortex following sensory deprivation. These microscopic and biochemical changes underpin the cortical release phenomenon that generates visual hallucinations in an otherwise structurally intact brain. Understanding these alterations emphasizes the neuroplastic nature of CBS and supports its distinction from neurodegenerative or psychotic disorders.

Toxicokinetics

CBS is not associated with direct toxin exposure or drug overdose; several neurochemical and pharmacokinetic mechanisms influence the onset, modulation, and resolution of visual hallucinations in this condition. These processes are primarily related to neurotransmitter dynamics, pharmacologic modulation, and drug-induced mimics of CBS-like phenomena.

1. Neurochemical Basis Relevant to Pharmacokinetics

CBS results from disinhibition of the visual cortex due to loss of afferent visual input. The underlying neurochemical balance between inhibitory (GABAergic) and excitatory (glutamatergic and serotonergic) neurotransmission is crucial. Pharmacologically, any agent or physiological change that alters these systems can influence CBS onset or severity:

• Reduced GABAergic tone → cortical hyperexcitability and hallucination generation.
• Increased glutamatergic activity (via N-methyl-D-aspartate [NMDA] and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors) → heightened spontaneous visual cortex firing.
• Altered serotonergic signaling (especially at 5-hydroxytryptamine receptors) → enhanced perceptual vividness, paralleling hallucinations seen with serotonergic psychedelics.[50]

2. Pharmacokinetic Modulators of CBS-Like Hallucinations

While CBS arises in structurally intact brains with visual deprivation, drug-induced CBS analogs have been documented, where pharmacokinetic factors play a role.

Table 5. Class, Mechanism, and Clinical Relevance for CBS Drugs 

5-HT2A, 5-hydroxytryptamine receptors; CBS, Charles Bonnet syndrome; CNS, central nervous system; GABA, gamma-aminobutyric acid; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor

These relationships underscore that CBS pathophysiology can be pharmacodynamically mimicked by agents altering inhibitory–excitatory neurotransmission kinetics.[51]

3. Drug Metabolism and Blood-Brain Barrier Permeability

In patients predisposed to CBS, systemic pharmacokinetics influence cortical susceptibility:

• Lipophilic compounds with high CNS penetration (eg, tricyclic antidepressants, opioids) may potentiate hallucinations.
• Age-related reductions in hepatic and renal clearance prolong exposure to the active metabolite, increasing the risk of perceptual disturbances.
• P-glycoprotein polymorphisms or reduced efflux capacity at the blood-brain barrier may increase local cortical drug concentrations, modulating neurotransmitter receptor kinetics.[52]

4. Visual Cortex Receptor Dynamics and Pharmacologic Targets

Histologic and neurochemical findings in CBS demonstrate upregulation of NMDA receptors and downregulation of GABA-A receptors. These receptor alterations have direct pharmacokinetic implications:

• Drugs enhancing GABAergic tone (eg, gabapentin, clonazepam) may reduce CBS frequency.
• Atypical antipsychotics (eg, quetiapine, olanzapine), through serotonin-dopamine receptor modulation, can normalize excitatory-inhibitory balance.
• SSRIs and 5-HT2A antagonists modulate serotonergic kinetics, improving cortical stability in some patients.

Hence, CBS management occasionally involves targeted pharmacologic modulation of neurotransmitter kinetics rather than treatment of an exogenous toxin.[53]

5. Endogenous Neurochemical “Toxicokinetics”

Endogenous neurotransmitters behave in a quasi-toxicokinetic fashion during CBS:

• Excess glutamate acts as an excitotoxin at high synaptic concentrations, contributing to cortical hypermetabolism observed on PET scans.
• Reduced GABA synthesis and inhibition of reuptake lead to diminished inhibitory tone.
• Serotonin accumulation in visual association areas enhances the vividness of visual imagery. These dynamic shifts in neurotransmitter levels mirror toxicokinetic profiles despite the absence of exogenous toxins.[54]

6. Clinical and Therapeutic Implications

Understanding the pharmacokinetic parallels of CBS has practical implications:

• Drug-induced hallucinations must be distinguished from true CBS by timing, reversibility, and presence of visual loss.
• Adjustment of medications with high CNS activity can prevent exacerbations.
• Agents such as SSRIs, antiepileptics, or atypical antipsychotics may be titrated considering their CNS half-lives, receptor affinities, and steady-state kinetics to optimize symptom control.[55]

Summary

While CBS does not involve external toxins, its neurochemical and pharmacokinetic environment mirrors toxicokinetic processes, where an imbalance between excitatory and inhibitory neurotransmission acts as an internal “biochemical toxin.” Understanding these kinetic mechanisms helps clinicians differentiate CBS from drug-induced hallucinosis and select appropriate pharmacologic interventions.

History and Physical

Patients with CBS will report a history of "release hallucinations," which is often synonymous with CBS, describing visual hallucinations that occur in individuals with vision loss related to the brain, optic nerve, or eye involvement.[29][56][57][58] Patients with chronic slow-progressing ocular disease typically report hallucinations at least 1 year after severe visual impairment or complete vision loss.[28][30][59] In comparison, patients with acute vision loss secondary to the optic nerve or brain damage will typically report hallucinations within hours or days of inciting events; however, hallucinations can still be reported within months as well.[60][61][62][63] 

Visual hallucinations can range from simple phenomena, such as light flashes, shapes, or lines, to complex forms, including formed images and scenes.[64][65] Furthermore, it has been reported that in patients with CBS in which vision loss was attributed to neurologic or retinal causes, simple hallucinations were more prevalent than complex ones at 90% and 37%, respectively.[62] Hallucinations are typically colored and range in the visual field from animated to static to moving en bloc. Patients will also report that hallucinations are more prevalent with the eyes open than closed.

Patients with CBS will also often report distress from their hallucinations, even though they frequently recognize them as unreal and disconnected from themselves. When obtaining a patient's history, it is essential to note that CBS is not associated with sensory or auditory hallucinations.[65] Moreover, the hallucinations observed in CBS can be typically complex or straightforward, even though a full complex spectrum of hallucinations can exist.[31] Simple hallucinations can be elementary or formed and composed of photopsia, a grid-like pattern, simple pattern shapes, or branching patterns.[59] Complex visual hallucinations are composed of lucid, detailed images of people, faces, animals, plants, flowers, trees, vehicles, and other objects.[56] Beyond the history of visual hallucinations, physical examination involves assessing visual processes and mechanisms underlying vision loss.[66]

In a study from London, 38% of the 492 subjects reported visual hallucinations as frightening, horrifying, and startling during the onset. With time, the emotional inputs to hallucinations reduced to 8%.[30] In 60% of patients, visual hallucinations didn't affect their lives, 33% said it had a negative impact, and 7% felt it had a good effect on their lives.[21] However, the definition of CBS mentions complex visual hallucinations. In clinical practice, patients frequently present with simple visual hallucinations.[31] Ophthalmologic examination, identifying features such as glaucoma, macular degeneration, cataracts, and retinal or optic nerve damage, can also be a critical component of the physical exam, as CBS requires concurrent visual impairment with reported visual hallucinations.[28] Neurological deficits observed in cerebrovascular accidents can also manifest as cortical damage, including involvement of the visual pathway, another crucial component of CBS.[21]

Patients with CBS typically present with visual hallucinations in the setting of partial or severe visual loss but without cognitive impairment or psychiatric illness. The onset is usually insidious, following a period of visual deprivation from ocular or neurological causes (see Table 6).

Key historical points include:

• Chief complaint: Recurrent, well-formed visual hallucinations such as people, animals, geometric patterns, or scenes.
• Duration and frequency: Episodes may last from seconds to hours and occur sporadically or daily.
• Nature of hallucinations:
• Formed and vivid (faces, figures, landscapes, buildings)
• Static or motionless; not interactive or responsive
• Often colorful, detailed, and described as “lifelike”
• Insight preserved: The patient usually recognizes that the hallucinations are unreal, differentiating CBS from psychosis.
• Triggers and alleviating factors:
• Often occur in dim light, sensory deprivation, or loneliness
• May diminish with increased visual stimulation (eg, turning on lights, moving eyes)
• Associated visual impairment: Most have underlying ocular or optic nerve disease, such as:
• Age-related macular degeneration
• Glaucoma
• Diabetic retinopathy
• Retinitis pigmentosa
• Optic neuropathy or cortical visual impairment
• Absence of: Auditory, tactile, or olfactory hallucinations, confusion, delusions, or mood disturbance
• Impact on quality of life: Some patients report anxiety or fear initially, while others find the visions benign or even comforting once reassured.[5]

Physical Examination Findings

The general neurological and psychiatric examinations are typically normal, with the following ophthalmic findings.

Table 6. System and Findings: CBS Examinations

Clinical Clues Supporting CBS Diagnosis

1. Presence of complex visual hallucinations (eg, faces, people, patterns).
2. Established visual loss due to ocular pathology.
3. Preserved cognition and insight (patient knows the images are not real).
4. Absence of other sensory hallucinations or psychotic features.

Differential Considerations to Exclude During History and Physical

• Delirium (acute confusion, fluctuating consciousness)
• Dementia with Lewy bodies (visual hallucinations + Parkinsonism)
• Temporal lobe epilepsy (brief, stereotyped visual phenomena)
• Psychiatric hallucinosis (loss of insight, multimodal hallucinations)
• Medication-induced hallucinations (eg, digoxin, anticholinergics)

In summary, the history and physical examination in CBS reveal a clear association between visual loss and complex visual hallucinations, with no evidence of psychiatric or neurological disease. The combination of preserved insight, normal cognition, and identifiable ocular pathology is diagnostic.[67]

Evaluation

The first step in evaluating for CBS is to assess for neurocognitive disorders and impairment, as well as neurological deficits, through a comprehensive neurological examination. The workup may include brain imaging, electroencephalography, laboratory tests, and genetic testing, depending on the suspected neurological condition. Upon ruling out hallucinations secondary to an underlying neurological condition or medication, the next step is confirming the presence of vision impairment or loss through a thorough ophthalmologic evaluation with visual field testing.[68]

A medication reconciliation assessment for hallucinations induced by medications should also be completed.[69] Some common nonpsychotropic medicines that have been found to cause hallucinations include beta-blockers, glucocorticoids, angiotensin-converting enzyme inhibitors, cimetidine, ranitidine, sildenafil, digoxin, carbapenems, penicillins, macrolides, cephalosporins, linezolid, and doxycycline.[70][71][72] The medication reconciliation must also include substances purchased over the counter, and patients must be asked about any supplements or drugs of abuse. 

Evaluating for CBS focuses on establishing the diagnosis by confirming the presence of visual hallucinations in a visually impaired but cognitively intact individual, while excluding psychiatric, neurological, or pharmacologic causes. The diagnosis is clinical, supported by targeted ophthalmic, neurologic, and neuroimaging assessments. There are no specific laboratory biomarkers; however, a systematic evaluation is essential to identify the underlying cause of visual impairment and to exclude organic brain pathology (see Table 7).

Diagnostic Criteria (Core Evaluation Framework)

CBS is primarily diagnosed based on the following core features, endorsed by the American Academy of Ophthalmology (2023) and the Royal College of Ophthalmologists (RCOphth). These 4 features form the clinical cornerstone of CBS diagnosis:

1. Presence of complex, formed, recurrent visual hallucinations (people, animals, landscapes, patterns)
2. Insight preserved, eg, the patient recognizes hallucinations are unreal
3. Absence of psychiatric illness, delirium, or dementia
4. Presence of partial visual loss due to ocular or optic pathway disease [73]

Clinical Evaluation

A thorough history and clinical examination are mandatory:

• Detailed history of visual hallucinations: Onset, frequency, nature, triggers (darkness, fatigue), and patient insight
• Past ocular history: Age-related macular degeneration, glaucoma, diabetic retinopathy, or other causes of visual loss
• Systemic and medication review: To exclude drug-induced hallucinations (dopaminergic, anticholinergic, or corticosteroid use)
• Mental status examination: To ensure cognitive integrity and absence of psychiatric disease [74]

Table 7. Key Clinical Differentiators of CBS

Ophthalmologic Evaluation

A complete ophthalmic assessment is essential to determine the degree and cause of visual impairment:

Visual Function Testing

• Visual acuity and contrast sensitivity (Snellen, Pelli-Robson chart)
• Visual field testing (Humphrey/Goldmann perimetry) to detect field constriction or scotomas [9]

Slit-Lamp and Fundus Examination

• Anterior segment evaluation to detect cataract, corneal opacity, or media haze
• Fundus examination for retinal or optic nerve pathology (ARMD, diabetic retinopathy, glaucoma)[75]

Retinal and Optic Nerve Imaging

• Optical coherence tomography to assess macular thickness, retinal pigment epithelium integrity, and optic nerve head changes
• Fundus photography to document lesions and atrophy
• Fluorescein angiography, when indicated, for vascular retinal disease

Visual Electrophysiology

These help confirm afferent pathway dysfunction:

• Visual evoked potential to assess optic nerve conduction
• Electroretinogram to assess photoreceptor function [76]

Neurological and Neuroimaging Evaluation

Although CBS is primarily ophthalmic, neuroimaging is recommended in atypical or new-onset cases, especially if accompanied by neurological signs.

Brain Imaging

• MRI (preferred):
• Rule out occipital lobe lesions, infarcts, tumors, or demyelinating disease.
• Evaluate for cortical atrophy patterns (exclude Alzheimer disease or Lewy body dementia).
• Functional MRI studies (in research settings) demonstrate occipital cortex hyperactivation during hallucinations.
• Computed tomography scan: For patients in whom MRI is contraindicated.[77]

Electroencephalogram

• Usually normal in CBS
• Performed if there is suspicion of epileptic visual hallucinations or temporal lobe seizures

Neuropsychological Testing

• Mini-Mental State Examination or Montreal Cognitive Assessment to confirm preserved cognition.
• Psychiatric evaluation to exclude psychosis, delirium, or depression [78]

Laboratory Evaluation

Although there are no specific laboratory markers, the following may be performed to exclude systemic causes:

• Blood glucose and HbA1c for diabetic retinopathy
• Lipid profile and erythrocyte sedimentation rate for vascular ocular disease
• Vitamin B12 and thyroid function tests to rule out metabolic encephalopathy mimics
• Toxicology screen if medication- or substance-related hallucinations are suspected

Diagnostic Exclusion (Rule-Out Conditions)

CBS is a diagnosis of exclusion (see Table 8). Differential diagnoses should be evaluated by combining clinical and investigative findings:[79]

Table 8. Condition and Evaluation Findings

EEG, electroencephalogram; MRI, magnetic resonance imaging; PET, positron emission tomography

Diagnostic Tools and Guidelines

International guidelines

• American Academy of Ophthalmology (AAO, 2023): Recommends ophthalmologic assessment, cognitive screening, and neuroimaging if visual hallucinations persist or insight fluctuates.
• National Institute for Health and Care Excellence (NICE, 2024): Suggests a 3-step evaluation:
  1. Confirm hallucination characteristics
  2. Assess the cause of vision loss 
  3. Rule out psychiatric disease
• Royal College of Ophthalmologists (RCOphth, UK, 2024): Endorses multidisciplinary evaluation involving ophthalmologists, neurologists, and psychologists to confirm CBS and educate patients about its benign nature.[37]

Optional Aancillary tests

• Functional MRI (research setting) demonstrates spontaneous occipital activation in the absence of retinal input.
• Positron Emission Tomography may reveal hypermetabolism in the visual cortex.
• Visual deprivation testing: Hallucinations may be reproducible in dark-adapted settings, supporting the diagnosis.[80]

Summary

The evaluation of CBS centers on:

1. Confirming visual hallucinations in a cognitively intact individual.
2. Documenting significant visual impairment.
3. Excluding psychiatric, neurological, or pharmacologic causes.
4. Employing targeted ophthalmic and neuroimaging tests guided by AAO and NICE recommendations.

This structured, exclusion-based diagnostic approach ensures accurate identification, avoids mislabeling as psychosis, and enables patient reassurance and targeted management.[81]

Treatment / Management

Treatment for CBS can vary depending on symptom severity. For mild symptoms, reassurance may be sufficient.[82] However, for more severe symptoms, treatment includes behavioral techniques and medications to suppress hallucinations. Studied techniques include blinking during hallucination or rapid eye movement from one object to another, away from the perceived hallucination field of vision.[39] The mainstay of management is clinician awareness and compassion.[66][83](B3)

Pharmacotherapy

Medications are often reserved for severe diseases, including those with disturbing or continuous hallucinations. Antipsychotics have been found to have mixed efficacy; however, atypical antipsychotics such as low doses of quetiapine or olanzapine are preferred due to safer adverse effect profiles, especially in older adults, who tend to be affected by CBS.[84][64] Other medications with good efficacy and minimal adverse effects include cholinesterase inhibitors such as donepezil. Medications with anecdotal evidence supporting their use in cyclic vomiting syndrome include antiepileptics such as valproate, carbamazepine, gabapentin, and clonazepam. Lastly, results from some small case series have identified promising medications, including venlafaxine, escitalopram, and cisapride.[85][86] Results from a recent randomized, placebo-controlled, crossover trial of transcranial direct current stimulation for CBS showed a positive effect and warrant further investigation.[87](A1)

Psychological Therapy

Techniques such as relaxation training, distraction, cognitive remodeling, and psychological therapy for the phantom phenomenon have been advocated to minimize the unpleasant and troublesome effects of visual hallucinations.

Reassurance and counselling

Individuals with CBS may experience anxiety and are usually unaware of the condition. Many patients may demonstrate negative emotions when meeting with healthcare professionals regarding their hallucinations.[88] Reassurance is necessary, as many patients are comforted when told that it's not a psychiatric phenomenon.[89](B3)

Optimizing Visual Function

An eyeglass and visual-aid prescription is necessary for optical correction, and cataract surgery may be required for visual acuity.[5] Managing CBS focuses on patient reassurance, visual rehabilitation, and, when necessary, targeted pharmacologic therapy. Since CBS arises from visual deprivation and cortical hyperexcitability, the principal aim is to improve visual input and reduce cortical disinhibition. Most patients benefit from education, environmental modification, and supportive therapy, while only a minority requires pharmacologic intervention.

General Management Principles

CBS is a benign, nonpsychotic condition that typically does not require aggressive treatment. The management approach is stepwise, beginning with reassurance and education before progressing to pharmacologic options.

Core principles include:

• Recognize and reassure: Clarify that hallucinations are a result of visual loss, not mental illness.
• Restore vision when possible: Address reversible causes such as cataract or refractive error.
• Reduce sensory deprivation by encouraging visual stimulation, adequate lighting, and engagement.
• Treat comorbid anxiety, depression, or sleep disturbance that can amplify hallucinations.[90]
(B3)

Patient Education and Reassurance (First-line Intervention)

This is the cornerstone of CBS management and endorsed by all major guidelines (AAO, NICE, RCOphth).

• Explanation of the phenomenon: Inform patients that CBS hallucinations are common in visual loss and do not imply insanity or dementia.
• Normalize the experience: This reduces fear and distress; most patients report significant relief upon reassurance.
• Family and caregiver education helps reduce misunderstandings and social withdrawal.[91]

AAO and NICE recommendations (2023–2024):

“Reassurance and education are first-line management for CBS and should be offered to all patients before pharmacologic therapy.”

Optimization of Visual Function

Improving visual input can often reduce or eliminate hallucinations.

Correct reversible ocular causes

• Cataract extraction, vitrectomy, or corneal procedures when indicated.
• Low-vision aids include magnifiers, contrast-enhancing devices, and ambient-illumination enhancement.[13]
(B3)

Visual rehabilitation

• Referral to a low-vision specialist for individualized optical or digital rehabilitation plans
• Adaptive devices (closed-circuit magnifiers, electronic readers) to enhance residual vision and reduce cortical “release” activity

Regular ophthalmic follow-up

• Monitor progression of underlying retinal or optic nerve disease.
• Reinforce the benign nature and expected course of CBS.[13]
(B3)

Behavioural and Nonpharmacologic Interventions

Nondrug measures shown in Table 9 below can help interrupt hallucination episodes and modulate cortical hyperactivity.

Table 9. Nondrug Measures to Interrupt Hallucination Episodes in CBS

Pharmacologic Management (Reserved for Distressing or Persistent CBS)

Pharmacologic therapy is considered only when hallucinations are intrusive, frightening, or disabling and persist despite reassurance and visual optimization. 

Antipsychotics (use cautiously)

• Atypical antipsychotics such as quetiapine (12.5–25 mg) or olanzapine (2.5–5 mg) may reduce hallucination frequency in selected patients.
• Typical antipsychotics (eg, haloperidol) are avoided due to extrapyramidal side effects, especially in older adults.
• Evidence: There are only small case series, limited by the absence of randomized trials.

Antidepressants

• SSRIs (eg, sertraline, citalopram) or tricyclic antidepressants (eg, amitriptyline) have shown benefit in reducing visual hallucinations in CBS by modulating serotonin levels.
• The mechanism includes downregulation of cortical 5-HT2A receptors implicated in visual perceptual processing.[92]

Antiepileptics/neuromodulators

• Gabapentin (300–900 mg/day) or carbamazepine can suppress cortical hyperexcitability and improve symptoms.
• Clonazepam may help in cases associated with anxiety or sleep disturbance.

Cholinesterase inhibitors

• Case reports suggest donepezil may improve CBS in patients with comorbid cognitive decline or age-related cortical atrophy.[3]

Management of Underlying and Contributing Conditions

• Depression or anxiety: Managed with psychotherapy or pharmacologic support (SSRIs).
• Sleep disturbance: Melatonin or mild sedatives may be used.
• Medication review: Avoid or reduce agents that exacerbate hallucinations (dopaminergics, anticholinergics, corticosteroids).[93]

Multidisciplinary and Supportive Approach

CBS benefits from an interdisciplinary care model:

• Ophthalmologist: Manages vision restoration and ocular disease
• Neurologist: Excludes cortical pathology; monitors neurocognitive status
• Psychiatrist/clinical psychologist: Provides coping strategies, reassurance, and behavioral therapy
• Occupational therapist: Assists with optimizing home lighting and the visual environment

International guidelines (RCOphth 2024) recommend joint follow-up by ophthalmology and neuro-ophthalmology teams for persistent or distressing CBS cases (see Tables 10 and 11).

Prognosis and Long-term Follow-up

• In most patients, hallucinations decrease spontaneously over 6–18 months as cortical adaptation occurs.
• Episodes often become less frequent and less vivid once patients understand the condition's benign nature.
• Persistent cases may require long-term low-dose pharmacotherapy and regular follow-up.[94]

Prognostic factors for remission:

• Partial restoration of vision
• Early recognition and reassurance
• Social and cognitive engagement
• Absence of neurodegenerative comorbidity [95]
(B3)

Table 10. Treatment Approach to CBS

CBT, cognitive behavioral therapy; SSRI, selective serotonin reuptake inhibitor

Table 11. Guideline-Based Recommendations for CBS

Managing CBS centers on reassurance, education, and vision restoration. Pharmacologic therapy is rarely needed and should be reserved for distressing, persistent hallucinations. Adherence to AAO, NICE, and RCOphth guidelines ensures a holistic, patient-centered approach that minimizes anxiety, improves quality of life, and supports visual and cognitive well-being.

Differential Diagnosis

Essential considerations for differential diagnosis include etiologies associated with visual hallucinations. These include the following:

• Narcolepsy
• Peduncular hallucinosis
• Epileptic seizures
• Neurodegenerative conditions: Parkinson and Alzheimer disease, and Lewy body dementia
• Metabolic encephalopathy: Drugs, alcohol withdrawal, or delirium
• Hypnagogic and hypnopompic hallucinations
• Migraine aura
• Schizophrenia
• Mood disorder with psychotic features

CBS is differentiated from the above conditions by the simultaneous presence of visual deficits and the absence of neurological deficits. Furthermore, CBS is differentiated by the absence of auditory or other sensory-associated hallucinations, as seen in many of the above differentials. CBS is a diagnosis of exclusion (see Table 12), and differentiation from psychiatric, neurologic, or drug-induced hallucinations is critical. The following table summarizes the key differentials and distinguishing clinical features.[9]

Table 12. Differential Diagnosis of Charles Bonnet Syndrome

EEG, electroencephalogram; L-DOPA, levodopa; MRI, magnetic resonance imaging; PET, positron emission tomography; REM, rapid eye movement

Key Diagnostic Differentiators

• Insight preserved in CBS
  • Patients recognize the unreal nature of hallucinations.
• Purely visual hallucinations (no auditory or tactile component) 
• Vision loss association, not psychiatric or metabolic derangements
• Normal cognition and mental status on MMSE/MoCA testing
• Normal neuroimaging except for preexisting ocular or optic pathway disease

Summary

CBS must be differentiated from psychiatric, epileptic, neurodegenerative, and metabolic causes of visual hallucinations. A comprehensive ophthalmic examination, cognitive assessment, and neuroimaging help confirm the diagnosis of CBS and exclude other etiologies.

Guideline Reference:

• AAO Preferred Practice Pattern, 2023: “Visual hallucinations in the elderly should first prompt evaluation for ocular pathology and preserved insight before considering psychiatric disease.”
• NICE Clinical Guidance 2024: “Exclude neurological and psychiatric causes systematically; confirm CBS only in cognitively intact patients with visual impairment.”[13]

Pertinent Studies and Ongoing Trials

There are no high-quality randomized controlled trials specific to CBS. Management is informed by observational studies, case series, case reports, and low-vision rehabilitation literature, as well as neuroimaging evidence of occipital hyperexcitability. Treatment is therefore stepwise: education/reassurance → visual optimization/rehabilitation → limited, symptom-driven pharmacotherapy (see Table 13).

Table 13. Evidence Map (Selected, Representative)

ARMD, age-related macular degeneration; CBS, Charles Bonnet syndrome; EPS, extrapyramidal symptoms; fMRI, functional magnetic resonance imaging; PET, positron emission tomography; SSRI, selective serotonin reuptake inhibitor

Why the current management is recommended:

• Reassurance + education consistently reduces distress; low risk; endorsed by AAO, RCOphth, and NICE guidance.
• Visual optimization and low-vision rehabilitation are the most effective nonpharmacological approaches for reducing cortical “release” by improving visual input.
• Targeted pharmacotherapy: Symptom-driven, short-term, shared decision-making due to limited evidence and adverse effects.[1]

Ongoing/Recent Research Themes (as of recent literature)

• Low-vision rehabilitation trials where hallucination burden is a secondary endpoint (ARMD cohorts)
• Neurophysiology of visual cortex disinhibition (EEG/MEG/fMRI paradigms), exploring biomarkers of response to light or visual tasks
• Drug repurposing case series (SSRIs, gabapentin, quetiapine) with standardized outcome scales (eg, frequency diaries, distress scores)
• Digital therapeutics (home-based lighting protocols, visual task apps) are under feasibility/acceptability evaluation

No radiotherapy (RT) studies exist for CBS; RT is not indicated. Current evidence prioritizes education, vision rehabilitation, environmental strategies, and selective pharmacologic therapy.[3]

Treatment Planning

The treatment plan for CBS should be individualized, multidisciplinary, and focused on reassurance, visual rehabilitation, and selective pharmacologic therapy (see Tables 13–16). The overarching aim is to alleviate distress, improve quality of life, and address the underlying cause of visual loss rather than merely suppress hallucinations. Treatment planning proceeds in 5 structured phases: recognition, education, vision optimization, behavioural modification, and, if required, pharmacologic support.

Phase I: Diagnosis Confirmation and Baseline Assessment

Before formulating a plan, confirm CBS through a systematic diagnostic approach:

• Establish the triad: complex visual hallucinations, visual impairment, and intact cognition.
• Exclude psychiatric illness, neurodegenerative disease, or drug-induced hallucinosis.
• Document:
• Frequency, nature, and emotional impact of hallucinations
• Degree of visual loss (best-corrected visual acuity, visual field)
• Cognitive assessment (MMSE/MoCA).
• Underlying ocular etiology (ARMD, glaucoma, diabetic retinopathy)   

Baseline tools:

• Optical coherence tomography/fundus imaging for ocular pathology
• MRI (if atypical)
• Psychiatric screen if insight is questionable

This establishes a reference for monitoring response to interventions.[91]

Phase II: Patient and Family Education

Primary intervention Education is the most effective initial treatment and is recommended by AAO and NICE as first-line therapy.

Counseling goals:

• Explain the benign nature of CBS and its association with visual loss.
• Reassure that hallucinations do not indicate mental illness or dementia.
• Encourage open discussion: Many patients underreport symptoms due to fear of stigmatization.

Family involvement Educate relatives to recognize CBS and support the patient emotionally, preventing mislabelling as psychotic or confused.[96]

Phase III: Vision Optimization and Environmental Modifications

Objective: Reduce cortical deafferentation and restore visual input.

Ophthalmic interventions:

• Treat reversible causes (eg, cataract extraction, correction of refractive error).
• Initiate low-vision rehabilitation with magnifiers, contrast enhancers, and adaptive lighting.
• Encourage use of ambient illumination (well-lit environments minimize hallucinations).[97]

Table 13. Environmental and Behavioural Adjustments for CBS

Follow-up: Reassess after 4–6 weeks for improvement in hallucination frequency or distress.

Phase IV: Pharmacologic Intervention (If Nonresponsive to Nondrug Measures)

Pharmacotherapy is reserved for patients with distressing, frequent, or functionally disabling hallucinations. Treatment choice depends on symptom burden, comorbidities, and tolerance.[98]

Table 14. Stepwise Pharmacologic Plan

5-HT2A, 5-hydroxytryptamine 2A receptor; CBS, Charles Bonnet syndrome; D2, dopamine D2 receptor; GABA, gamma-aminobutyric acid; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant 

Monitoring

• Follow up at 2 to 4 weeks to assess for adverse effects and to track symptoms.
• Gradual taper after 6 to 12 weeks of stability.

Phase V: Psychosocial and Multidisciplinary Support

Psychological counseling Cognitive-behavioral therapy (CBT) or supportive psychotherapy can reduce distress and improve coping.

Support groups Referral to low-vision or CBS peer groups improves patient confidence and adherence.[99]

Table 15. Multidisciplinary follow-up team

Long-Term Monitoring and Outcome Evaluation

Monitoring parameters:

• Visual acuity and field stability.
• Frequency and vividness of hallucinations.
• Psychological adaptation and insight preservation.

Outcome expectations:

• Most patients experience gradual remission within 12 to 18 months as cortical adaptation stabilizes.
• Persistent CBS may require ongoing low-dose pharmacotherapy.
• Prognosis is excellent with reassurance and visual rehabilitation.[9]

Table 16. Summary Treatment Flow (AAO–NICE–RCOphth Integrated Model)

Toxicity and Adverse Effect Management

• Although CBS is primarily managed through reassurance and vision rehabilitation, pharmacologic therapy may occasionally be required for distressing or persistent hallucinations. Because such medications act on central neurotransmitter pathways, clinicians must anticipate, monitor, and manage potential toxicities and adverse effects—especially in older, visually impaired adults who are often on multiple medications.

General Principles

• Start low and go slow: Initiate all psychotropic or neuromodulatory drugs at the lowest effective dose and titrate cautiously.
• Single-agent approach: Avoid polypharmacy and the concomitant use of sedatives or anticholinergics.
• Periodic review: Reassess need for continued therapy every 6 to 8 weeks.
• Educate patients and caregivers by discussing the expected benefits, potential adverse effects, and early signs of toxicity (see Table 17).
• Monitor for falls, cognitive blunting, and metabolic disturbances, which are more common in older adult patients with CBS.[100]

Table 17. Drug-Specific Toxicity and Management for CBS

BP, blood pressure; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; ECG, electrocardiogram; FDA, Food and Drug Administration; GABA, gamma-aminobutyric acid; GI, gastrointestinal; HR, heart rate; LFT, liver function test; QI, quality improvement; SIADH, syndrome of inappropriate antidiuretic hormone secretion; SSRI, selective serotonin reuptake inhibitor

Strategies for Preventing Adverse Events

1. Baseline evaluation: Check liver, renal, and cardiac function before initiating psychotropics.
2. Avoid drug–drug interactions, especially if taking SSRIs (cytochrome P450 inhibition) and carbamazepine (enzyme inducer).
3. Review concomitant medications: Avoid duplication with sedatives, opioids, or anticholinergics.
4. Monitor cognition and mobility: Hallucination control should not be achieved at the expense of functional decline.
5. Adjust for comorbidities: Reduce doses in renal impairment (gabapentin) or hepatic dysfunction (antipsychotics, SSRIs).
6. Gradual withdrawal: Abrupt discontinuation of antiepileptics or benzodiazepines can precipitate rebound symptoms or seizures.[101]

Adverse Reaction Management

• Mild symptoms (eg, nausea, lightheadedness): Reassure, administer with food, reduce dose
• Moderate symptoms (eg, excessive sedation, orthostatic hypotension): Step down dose or switch class.
• Severe reactions (eg, arrhythmias, severe hyponatremia, delirium): Discontinue drug, provide supportive care, and report adverse event.
• Metabolic toxicity: Manage per standard diabetes/lipid guidelines; consult a clinician if weight gain or glucose intolerance appears.

Nonpharmacologic Safety Measures

Even during pharmacologic therapy, prioritize:

• Achieving adequate hydration, nutrition, and mobility exercises.
• Avoiding dim lighting and visual deprivation that can intensify hallucinations.
• Encouraging consistent medication timing and adherence using large-print or color-coded schedules.
• Reassessing drug necessity regularly, as many patients can discontinue therapy once hallucinations remit.[102]

Reporting and Pharmacovigilance

• Adverse effects should be reported to national pharmacovigilance programs (eg, the FDA MedWatch program and the World Health Organization Uppsala Monitoring Centre).
• Document drug-related hallucination changes or adverse reactions in the medical record for longitudinal tracking.

Toxicity management in CBS revolves around judicious drug selection, vigilant monitoring, and early dose adjustment. Non-pharmacologic interventions remain the mainstay, and pharmacologic therapy should always be short-term, goal-directed, and regularly reviewed. The guiding principle: “Treat the distress, not the hallucination itself.”[103]

Staging

While CBS lacks a universally accepted formal staging system, several authors and neuro-ophthalmic studies have described distinct clinical phases based on symptom evolution, hallucinatory characteristics, and patient adaptation. These stages reflect the neurocortical adaptation process following visual sensory deprivation (see Table 18).

Conceptual Basis for Staging

CBS typically follows a self-limited course, progressing from onset after visual loss to adaptation or remission over months to years. Staging helps clinicians:

• Anticipate the natural history of symptoms
• Guide counseling and treatment planning
• Differentiate benign CBS from psychiatric or neurodegenerative hallucinations [17]

Table 18. Proposed Clinical Staging of CBS

Severity-Based Classification (Functional Staging Approach)

A pragmatic staging system (used in low-vision rehabilitation literature) classifies CBS by severity and functional impact rather than duration (see Table 19).

Table 19. Severity Grade, Functional Description, Impact, and Management Priority for CBS

Alternative Neurofunctional Model

Functional neuroimaging studies suggest a parallel 3-phase cortical progression:

1. Cortical hyperexcitability phase: Overactivation of visual association areas (V2–V5) after afferent loss.
2. Spontaneous visual generation phase: Aberrant pattern activation gives rise to conscious visual imagery.
3. Inhibitory reorganization phase: Gradual normalization via cortical adaptation and neuroplasticity.

This pathophysiologic sequence aligns with the clinical stages of onset → peak → adaptation.[13]

Clinical Utility of Staging

• Patient counseling: Explaining the stages helps reassure patients that their symptoms typically improve over time.
• Treatment selection:
  • Stage I–II → Nonpharmacologic (education, environmental modification).
  • Stage III (persistent/distressing) → Pharmacologic modulation.
• Follow-up planning: Periodic reassessment every 4 to 6 weeks until stabilization.[3]

CBS follows a 3-stage clinical evolution—beginning with early visual deprivation phenomena, progressing to vivid formed hallucinations, and eventually stabilizing with cortical adaptation. Severity staging (mild, moderate, severe) helps tailor management intensity, while recognizing the natural resolution phase prevents overtreatment.[1]

Prognosis

The prognosis of CBS largely depends on the underlying cause of vision impairment or loss, with multiple symptoms associated with chronic ocular disease lasting multiple years.[38] The prognosis is better in conditions in which visual impairment can be corrected promptly, such as cataract.[85][104] The prognosis of CBS can be variable, with remitting visual hallucinations in those with slow-progressing or stable vision impairment.[38] The individuals usually affected in this variable fashion are those affected by cerebrovascular accidents, with many having hallucinations lasting from a few weeks to a few days.[39] Other than the visual hallucinations associated with CBS, the condition has also been associated with the development of dementia. One study showing this association had resulted in 26% of individuals with CBS developing dementia at an average of 33 months.[105]

CBS is a benign, self-limiting condition in the majority of patients. The overall prognosis is excellent, with most individuals experiencing spontaneous reduction or complete resolution of hallucinations once cortical adaptation occurs or visual function improves. The key determinants of prognosis are the degree of visual impairment, the underlying ocular pathology, and the patient’s psychological adjustment to vision loss.

Natural Course and Duration

• Typical course: CBS follows a fluctuating but improving trajectory.
• Onset: Typically, onset occurs within weeks to months of the onset or progression of visual loss.
• Duration: Hallucinations commonly persist for 6 to 18 months, although some cases may continue for several years, particularly in those with advanced or irreversible visual loss.
• Resolution: Up to 60% to 80% of patients report partial or complete remission within 1 to 2 years, either spontaneously or following visual rehabilitation.[18]

Favourable Prognostic Indicators

Patients are more likely to experience remission if they have:

• Mild to moderate visual impairment rather than total blindness
• Reversible causes of vision loss (eg, cataract, diabetic macular edema)
• High insight and psychological resilience, reducing distress and avoidance behavior
• Early diagnosis and reassurance prevent anxiety-related exacerbation
• Improved visual input through corrective surgery or low-vision aids
• Active social engagement and exposure to visually stimulating environments

Clinical note: Improvement in lighting, contrast enhancement, or vision restoration (eg, cataract extraction) can lead to the rapid disappearance of hallucinations within weeks (see Table 20).[106]

Poor Prognostic Indicators/Risk of Persistence

Persistence or worsening of CBS is associated with:

• Severe bilateral visual loss: Advanced ARMD, retinitis pigmentosa, optic neuropathy
• Sudden and irreversible loss of visual input: Retinal artery occlusion
• Advanced age (>80 years) with cortical atrophy or poor neuroplasticity
• Social isolation and depressive symptoms
• Cognitive decline or neurodegenerative disease: Mild cognitive impairment, dementia with Lewy bodies
• Absence of reassurance or misdiagnosis as psychosis, leading to heightened anxiety and prolonged distress [107]

Table 20. Long-Term Outcomes

Psychological and Social Prognosis

• Emotional adaptation: With proper education, most patients learn to accept and ignore hallucinations, minimizing distress.
• Psychiatric morbidity: Unrecognized CBS may lead to secondary anxiety or depressive symptoms; however, these improve with diagnosis and reassurance.
• Cognitive prognosis: CBS itself does not indicate or predict dementia, though concurrent cognitive impairment may prolong symptom duration.[108]

Prognosis After Treatment

• Reassurance and education lead to a significant reduction in distress in nearly all patients.
• Visual rehabilitation enhances adaptation, with symptom-reduction success rates exceeding 70%.
• Pharmacologic therapy (SSRIs, gabapentin, or quetiapine) is effective in selected refractory cases but not required in the majority.
• Multidisciplinary follow-up promotes earlier recovery and prevents misclassification as a psychiatric illness.[109]

Table 21. Summary of Prognostic Expectations

Overall Prognosis

CBS has a favorable long-term prognosis. The condition does not progress to psychosis or dementia, and most patients regain functional independence once reassured and treated appropriately. Early recognition, compassionate counseling, and visual optimization remain the cornerstones of successful outcomes.

Complications

CBS is described and understood as a transient condition not associated with significant adverse consequences or complications outside of worsening hallucinations (see Table 22). CBS complications primarily concern the psychological effects of the illusions patients experience. Patients often do not inform medical staff or family, and may grow concerned that they have developed a mental illness. Results from a study showed that approximately 32% of those with CBS are emotionally distressed by their hallucination.[38] Although CBS is a benign and self-limiting condition, complications may arise from its psychological, social, and diagnostic impact rather than from the hallucinations themselves. These complications primarily result from misinterpretation, lack of awareness, and associated emotional distress.

Table 22. Complications of Charles Bonnet Syndrome

Summary

• CBS complications are functional and emotional, not structural or life-threatening.
• The most frequent complication is psychological distress, affecting up to one-third of patients.
• Early education, reassurance, and multidisciplinary care significantly reduce the risk of secondary anxiety, depression, and misdiagnosis.