CHARLES BONNET SYNDROME ASSOCIATED WITH AGE-RELATED MACULAR DEGENERATION Jeffrey G. Eng, MD,* Kenneth R. Diddie, MD,† Alfredo A. Sadun, MD, PHD*
Purpose: The visual hallucinations in Charles Bonnet syndrome (CBS) are most commonly attributed to release phenomena that arise due to a paucity of sensory input to visual association areas of the cerebral cortex (Cogan’s sensory deprivation theory of visual hallucinations). The authors wished to gain further insight into this mechanism behind CBS by examining a patient who experienced reversible visual hallucinations. Methods: The authors present a 77-year-old man with a history of severe age-related macular degeneration who experienced formed and moving visual hallucinations associated with CBS shortly after a retinal pigment epithelial detachment (RPED) in his right eye. His visual acuity had been reduced to 20/400 in the right eye. Results: Visual acuity improved to 20/50 in the right eye after a series of Macugen injections led to RPED resolution as evidenced by optical coherence tomography and fluorescein angiography. The visual hallucinations abruptly ceased after this dramatic improvement in visual acuity. Conclusion: Reestablishment of high resolution visual input leads to a dramatic and almost immediate increase in the stimulus threshold of visual cortex cells as reflected by resolution of symptoms. The subthreshold signals that reach consciousness to produce visual hallucinations in CBS are thus immediately mitigated. RETINAL CASES & BRIEF REPORTS 2:130 –132, 2008
From the *Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, and †Retinal Consultants of Southern California Medical Group, Inc., Westlake Village, California.
input to visual association areas of the cerebral cortex: that is, in compensation for deafferentation, the threshold for discharge of visual cortex cells decreases until spontaneous firing occurs. Thus, damage anywhere along the central visual pathway that results in significant visual impairment can potentially cause CBS. We describe a man diagnosed with CBS whose symptoms varied in direct connection to treatment and complications associated with age-related macular degeneration.
C
harles Bonnet syndrome (CBS) is characterized by complex visual hallucinations, widely varying in content but most commonly involving the image of a moving animal or person. Affected patients often have significant visual impairments, good insight into the unreal nature of their visual hallucinations, normal cognition, and no history of psychiatric illness. There are numerous theories of pathogenesis for CBS, but the most commonly accepted is the sensory deprivation theory of visual hallucinations proposed by Cogan.1 This theory attributes visual hallucinations to release phenomena that arise due to a lack of sensory
Case Report A 77-year-old man had a several-year history of severe agerelated macular degeneration. The patient had good cognitive function and no history of psychiatric illness. He had a large diskiform scar formation from age-related macular degeneration involving the entire macular region in the left eye. Visual acuity was 20/25 in the right eye and counting fingers at 2 ft in the left eye. The right eye remained unaffected until the patient noticed increasing difficulty with contrast while reading and blurred vision while driving. Funduscopy and optical coherence tomography revealed a large
The authors do not have any proprietary interest in this work. Reprint requests: Jeffrey G. Eng, MD, Doheny Eye Institute, 1355 San Pablo Street, DVRC 311, Los Angeles, CA.
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Fig. 1. A, Horizontal optical coherence tomography (OCT) scan through the center of the right macula shows a large retinal pigment epithelial detachment (PED). B, Fluorescein angiogram demonstrates the same retinal PED in the center of the macula with increased vascular leakage. C, Horizontal OCT scan through the same spot ⬇4 months later and after four pegaptanib injections shows that the retinal PED is largely resolved, correlating with improvement in visual acuity. D, Fluorescein angiogram after four pegaptanib injections shows decreased vascular leakage in the central macula of the right eye.
pigment epithelial detachment (PED) in the right eye (Fig. 1A). Subsequent fluorescein angiography showed choroidal neovascularization with fluorescein leakage involving the fovea in the right eye (Fig. 1B). Visual acuity at this point was 20/400 in the right eye and hand motion in the left eye. He was unable to visualize the Amsler grid and could read 2 of 14 and 0 of 14 right eye and left eye Ishihara color plates, respectively. The patient was treated with three pegaptanib (Macugen, Eyetech Pharmaceuticals, New York, NY) injections in the right eye over the next 3 months and had little to no improvement in visual acuity. At a follow-up 4 months after the PED and detection of choroidal neovascularization in the right eye, the patient reported formed and moving visual hallucinations typically involving flowered wallpaper, stripes, and other complicated color patterns that filled up the entire visual field. The patient was alert and oriented, and results of a stroke workup were negative. He retained good insight into the unreal nature of the patterns and demonstrated relief upon learning that CBS was the cause of his visual hallucinations. A fourth pegaptanib injection was given in the right eye. At a follow-up visit 3 weeks later, the visual hallucinations had resolved in association with improvement in visual acuity to 20/50 in the right eye and 20/400 in the left eye. Optical coherence tomography showed dramatic healing of the PED (Fig. 1C). Fluorescein angiography disclosed central staining in both eyes but diminished leakage from choroidal neovascularization in the right eye (Fig. 1D).
Discussion We describe a 77-year-old man with bilateral agerelated macular degeneration who had visual hallucinations consistent with CBS 4 months after deterioration of vision to 20/400 in the right eye and hand motion in the left eye. Two observations merit special consideration in our case. First, the visual hallucinations started after the PED severely diminished vision in the previously unaffected right eye. The patient had been dependent on the right eye for vision, because
visual acuity in the left eye was hand motion. Second, the visual hallucinations ceased within 3 weeks after visual acuity in the right eye improved to 20/50. The sequence of events emphasizes some of the key characteristics of CBS. CBS occurs more frequently in bilateral rather than unilateral ocular disease2 and with increasing severity of visual impairment.3 Our patient no longer had visual hallucinations once the PED resolved in conjunction with pegaptanib therapy and improvement in visual acuity in the right eye. This case is particularly interesting because of the association between visual acuity (as determined by the condition of the PED) and onset/cessation of visual hallucinations. To our knowledge, this temporal association and sudden response to pegaptanib treatment has never been so clearly demonstrated in a case of age-related macular degeneration. Findings of optical coherence tomography and fluorescein angiography in this case support the patient’s claim that the onset and disappearance of hallucinations occurred at approximately the same time as the decline and improvement of vision, respectively. The PED in our patient reduced sensory input to the brain and thus allowed normally inhibited activity to reach consciousness in the form of hallucinations. The patient reported no hallucinations once visual input to the brain was reestablished when the PED resolved. The almost immediate disappearance of visual hallucinations after reestablishment of visual input to the brain gives us more insight into the mechanism of CBS. As mentioned previously, sensory deprivation is the most accepted theory of pathogenesis for CBS.
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Our patient had deafferentation with the decline of vision in his right eye. The onset of his hallucinations occurred as a consequence of this deafferentation and subsequent decrease in the stimulus threshold for discharge of visual cortex cells. However, our patient’s visual hallucinations resolved within 3 weeks after significant improvement in visual acuity. This would suggest that with reestablishment of strong visual input, the stimulus threshold of visual cortex cells increases dramatically and almost immediately, in contrast with the subthreshold signals that are responsible for CBS. This is supported by the finding that shortterm (3 hours) light deprivation resulted in a significant decrease in the phosphene threshold within the occipital cortex but that these phosphene thresholds returned to normal values within 3 hours after reexposure to light.4 The current case demonstrates that the transient enhanced excitability within the visual cortex can be quickly reversed with the application of a strong stimulus. To our knowledge, this has never been shown in macular degeneration. The fluctuation in visual acuity correlating with the onset and disappearance of visual hallucinations has been clearly demonstrated only in a few other cases. An elderly woman with bilateral advanced cataracts had visual hallucinations that abruptly stopped after cataract extraction.5 Another woman had visual hallucinations 1 month after the onset of complete blindness in both eyes secondary to optic neuritis associated with multiple sclerosis.6 These hallucinations disappeared when vision spontaneously recovered in both eyes. Visual hallucinations have also been reported immediately after macular translocation when the retina remained detached and visual acuity was poor.7 These hallucinations disappeared upon reattachment of the retina.
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The current case as well as those just referenced reinforces that management of CBS should be focused on patient reassurance/counseling and treating the underlying cause of the visual deficit. The visual hallucinations can quickly disappear with reestablishment of strong visual input that results in the almost immediate normalization of visual cortex excitability and exclusion of the subthreshold stimuli responsible for CBS. Other treatment modalities, such as pharmacotherapy, directly aimed at treating the hallucinations of CBS should probably be reserved for unusually perturbing situations and where visual input cannot be reestablished. Key words: age-related macular degeneration, Charles Bonnet syndrome, pegaptanib (Macugen), sensory deprivation theory. References 1.
2.
3. 4.
5.
6.
7.
Cogan DG. Visual hallucinations as release phenomena. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1973;188: 139–150. Brown GC, Murphy RP. Visual symptoms associated with choroidal neovascularization. Arch Ophthalmol 1992;110: 1251–1256. Girkin CA, Miller NR. Central disorders of vision in humans. Surv Ophthalmol 2001;45:379–405. Boroojerdi B, Bushara KO, Corwell B, et al. Enhanced excitability of the human visual cortex induced by short-term light deprivation. Cereb Cortex 2000;10:529–534. Olbrich HM, Lodemann E, Engelmeier MP. Optical hallucinations in the aged with diseases of the eye. Z Gerontol 1987;20:227–229. Komeima K, Kameyama T, Miyake Y. Charles Bonnet syndrome associated with a first attack of multiple sclerosis. Jpn J Ophthalmol 2005;49:533–534. Eong KA, Fujii GY, Ng EWM, et al. Transient formed visual hallucinations following macular translocation for subfoveal choroidal neovascularization secondary to age-related macular degeneration. Am J Ophthalmol 2001;131:664–666.
Purpose: The visual hallucinations in Charles Bonnet syndrome (CBS) are most commonly attributed to release phenomena that arise due to a paucity of sensory input to visual association areas of the cerebral cortex (Cogan’s sensory deprivation theory of visual hallucinations). The authors wished to gain further insight into this mechanism behind CBS by examining a patient who experienced reversible visual hallucinations. Methods: The authors present a 77-year-old man with a history of severe age-related macular degeneration who experienced formed and moving visual hallucinations associated with CBS shortly after a retinal pigment epithelial detachment (RPED) in his right eye. His visual acuity had been reduced to 20/400 in the right eye. Results: Visual acuity improved to 20/50 in the right eye after a series of Macugen injections led to RPED resolution as evidenced by optical coherence tomography and fluorescein angiography. The visual hallucinations abruptly ceased after this dramatic improvement in visual acuity. Conclusion: Reestablishment of high resolution visual input leads to a dramatic and almost immediate increase in the stimulus threshold of visual cortex cells as reflected by resolution of symptoms. The subthreshold signals that reach consciousness to produce visual hallucinations in CBS are thus immediately mitigated. RETINAL CASES & BRIEF REPORTS 2:130 –132, 2008
From the *Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, and †Retinal Consultants of Southern California Medical Group, Inc., Westlake Village, California.
input to visual association areas of the cerebral cortex: that is, in compensation for deafferentation, the threshold for discharge of visual cortex cells decreases until spontaneous firing occurs. Thus, damage anywhere along the central visual pathway that results in significant visual impairment can potentially cause CBS. We describe a man diagnosed with CBS whose symptoms varied in direct connection to treatment and complications associated with age-related macular degeneration.
C
harles Bonnet syndrome (CBS) is characterized by complex visual hallucinations, widely varying in content but most commonly involving the image of a moving animal or person. Affected patients often have significant visual impairments, good insight into the unreal nature of their visual hallucinations, normal cognition, and no history of psychiatric illness. There are numerous theories of pathogenesis for CBS, but the most commonly accepted is the sensory deprivation theory of visual hallucinations proposed by Cogan.1 This theory attributes visual hallucinations to release phenomena that arise due to a lack of sensory
Case Report A 77-year-old man had a several-year history of severe agerelated macular degeneration. The patient had good cognitive function and no history of psychiatric illness. He had a large diskiform scar formation from age-related macular degeneration involving the entire macular region in the left eye. Visual acuity was 20/25 in the right eye and counting fingers at 2 ft in the left eye. The right eye remained unaffected until the patient noticed increasing difficulty with contrast while reading and blurred vision while driving. Funduscopy and optical coherence tomography revealed a large
The authors do not have any proprietary interest in this work. Reprint requests: Jeffrey G. Eng, MD, Doheny Eye Institute, 1355 San Pablo Street, DVRC 311, Los Angeles, CA.
130
131
CBS IN AMD
Fig. 1. A, Horizontal optical coherence tomography (OCT) scan through the center of the right macula shows a large retinal pigment epithelial detachment (PED). B, Fluorescein angiogram demonstrates the same retinal PED in the center of the macula with increased vascular leakage. C, Horizontal OCT scan through the same spot ⬇4 months later and after four pegaptanib injections shows that the retinal PED is largely resolved, correlating with improvement in visual acuity. D, Fluorescein angiogram after four pegaptanib injections shows decreased vascular leakage in the central macula of the right eye.
pigment epithelial detachment (PED) in the right eye (Fig. 1A). Subsequent fluorescein angiography showed choroidal neovascularization with fluorescein leakage involving the fovea in the right eye (Fig. 1B). Visual acuity at this point was 20/400 in the right eye and hand motion in the left eye. He was unable to visualize the Amsler grid and could read 2 of 14 and 0 of 14 right eye and left eye Ishihara color plates, respectively. The patient was treated with three pegaptanib (Macugen, Eyetech Pharmaceuticals, New York, NY) injections in the right eye over the next 3 months and had little to no improvement in visual acuity. At a follow-up 4 months after the PED and detection of choroidal neovascularization in the right eye, the patient reported formed and moving visual hallucinations typically involving flowered wallpaper, stripes, and other complicated color patterns that filled up the entire visual field. The patient was alert and oriented, and results of a stroke workup were negative. He retained good insight into the unreal nature of the patterns and demonstrated relief upon learning that CBS was the cause of his visual hallucinations. A fourth pegaptanib injection was given in the right eye. At a follow-up visit 3 weeks later, the visual hallucinations had resolved in association with improvement in visual acuity to 20/50 in the right eye and 20/400 in the left eye. Optical coherence tomography showed dramatic healing of the PED (Fig. 1C). Fluorescein angiography disclosed central staining in both eyes but diminished leakage from choroidal neovascularization in the right eye (Fig. 1D).
Discussion We describe a 77-year-old man with bilateral agerelated macular degeneration who had visual hallucinations consistent with CBS 4 months after deterioration of vision to 20/400 in the right eye and hand motion in the left eye. Two observations merit special consideration in our case. First, the visual hallucinations started after the PED severely diminished vision in the previously unaffected right eye. The patient had been dependent on the right eye for vision, because
visual acuity in the left eye was hand motion. Second, the visual hallucinations ceased within 3 weeks after visual acuity in the right eye improved to 20/50. The sequence of events emphasizes some of the key characteristics of CBS. CBS occurs more frequently in bilateral rather than unilateral ocular disease2 and with increasing severity of visual impairment.3 Our patient no longer had visual hallucinations once the PED resolved in conjunction with pegaptanib therapy and improvement in visual acuity in the right eye. This case is particularly interesting because of the association between visual acuity (as determined by the condition of the PED) and onset/cessation of visual hallucinations. To our knowledge, this temporal association and sudden response to pegaptanib treatment has never been so clearly demonstrated in a case of age-related macular degeneration. Findings of optical coherence tomography and fluorescein angiography in this case support the patient’s claim that the onset and disappearance of hallucinations occurred at approximately the same time as the decline and improvement of vision, respectively. The PED in our patient reduced sensory input to the brain and thus allowed normally inhibited activity to reach consciousness in the form of hallucinations. The patient reported no hallucinations once visual input to the brain was reestablished when the PED resolved. The almost immediate disappearance of visual hallucinations after reestablishment of visual input to the brain gives us more insight into the mechanism of CBS. As mentioned previously, sensory deprivation is the most accepted theory of pathogenesis for CBS.
132
RETINAL CASES & BRIEF REPORTSℜ
Our patient had deafferentation with the decline of vision in his right eye. The onset of his hallucinations occurred as a consequence of this deafferentation and subsequent decrease in the stimulus threshold for discharge of visual cortex cells. However, our patient’s visual hallucinations resolved within 3 weeks after significant improvement in visual acuity. This would suggest that with reestablishment of strong visual input, the stimulus threshold of visual cortex cells increases dramatically and almost immediately, in contrast with the subthreshold signals that are responsible for CBS. This is supported by the finding that shortterm (3 hours) light deprivation resulted in a significant decrease in the phosphene threshold within the occipital cortex but that these phosphene thresholds returned to normal values within 3 hours after reexposure to light.4 The current case demonstrates that the transient enhanced excitability within the visual cortex can be quickly reversed with the application of a strong stimulus. To our knowledge, this has never been shown in macular degeneration. The fluctuation in visual acuity correlating with the onset and disappearance of visual hallucinations has been clearly demonstrated only in a few other cases. An elderly woman with bilateral advanced cataracts had visual hallucinations that abruptly stopped after cataract extraction.5 Another woman had visual hallucinations 1 month after the onset of complete blindness in both eyes secondary to optic neuritis associated with multiple sclerosis.6 These hallucinations disappeared when vision spontaneously recovered in both eyes. Visual hallucinations have also been reported immediately after macular translocation when the retina remained detached and visual acuity was poor.7 These hallucinations disappeared upon reattachment of the retina.
●
2008
●
VOLUME 2
●
NUMBER 2
The current case as well as those just referenced reinforces that management of CBS should be focused on patient reassurance/counseling and treating the underlying cause of the visual deficit. The visual hallucinations can quickly disappear with reestablishment of strong visual input that results in the almost immediate normalization of visual cortex excitability and exclusion of the subthreshold stimuli responsible for CBS. Other treatment modalities, such as pharmacotherapy, directly aimed at treating the hallucinations of CBS should probably be reserved for unusually perturbing situations and where visual input cannot be reestablished. Key words: age-related macular degeneration, Charles Bonnet syndrome, pegaptanib (Macugen), sensory deprivation theory. References 1.
2.
3. 4.
5.
6.
7.
Cogan DG. Visual hallucinations as release phenomena. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1973;188: 139–150. Brown GC, Murphy RP. Visual symptoms associated with choroidal neovascularization. Arch Ophthalmol 1992;110: 1251–1256. Girkin CA, Miller NR. Central disorders of vision in humans. Surv Ophthalmol 2001;45:379–405. Boroojerdi B, Bushara KO, Corwell B, et al. Enhanced excitability of the human visual cortex induced by short-term light deprivation. Cereb Cortex 2000;10:529–534. Olbrich HM, Lodemann E, Engelmeier MP. Optical hallucinations in the aged with diseases of the eye. Z Gerontol 1987;20:227–229. Komeima K, Kameyama T, Miyake Y. Charles Bonnet syndrome associated with a first attack of multiple sclerosis. Jpn J Ophthalmol 2005;49:533–534. Eong KA, Fujii GY, Ng EWM, et al. Transient formed visual hallucinations following macular translocation for subfoveal choroidal neovascularization secondary to age-related macular degeneration. Am J Ophthalmol 2001;131:664–666.
