Dear Editor

I thank Dr Tomsak for his reply[1] to my comments.[2]

In response to point one,we agree that historically CBS is a disorder described in the elderly, but as we mentioned in our previous reply, this can easily be explained by the higher incidence of visual loss in the elderly. Further, without formal child pyschiatry review it is difficult to give a incidence in the childhood of CBS. As you would expect the very young may not be able to differentiate between complex visual hallucinations described by most elderly patients as a very real phenomenon. Children may simply regard these are real visual stimuli and not hallucinations. The literature does not support the diagnosis of CBS on age alone. Secondly, we support the point that editorial constraints limited the paper somewhat. However, point three still seems to be a point of contention. In the abscence of Brimonidine drops, the diagnosis of CBS would have been justified. However, the onset and remission of CBS with starting and stopping of brimonidine drops leads to support the fact that these hallucinations are simply a pyscho-pharmakinetic response, as would be expected by any medication penetrating the blood-brain barrier. Indeed, as we described in our previous reply Brimonidine, and drugs of the same class, have been shown to cause neuropysciatric phenomenon similar to CBS, and that this effect described by the authours support this point of visual hallucinations as a side effect of brimonidine tartrate. We reiterate our point that these four patients suffered side effects and not CBS, as current literature does not support this view.

References

(1) Tomsak RL. Charles Bonnet Syndrome - Author reply [electronic response to RL Tomsak, CR Zaret, and D Weidenthal; Charles Bonnet syndrome precipitated by brimonidine tartrate eye drops] bjophthalmol.com 2004http://bjo.bmjjournals.com/cgi/eletters/87/7/917#204

(2) Rahman I, Fernando BS, Harrison M. Charles Bonnet Syndrome and brimonidine: comments [electronic response to RL Tomsak, CR Zaret, and D Weidenthal; Charles Bonnet syndrome precipitated by brimonidine tartrate eye drops] bjophthalmol.com 2004http://bjo.bmjjournals.com/cgi/eletters/87/7/917#189

Dear Editor

I thank Dr Rahman and his colleagues for their comments.

1. Clinically and historically Charles Bonnet Syndrome (CBS) is indeed a disorder of the elderly, in spite of rare reports of the syndrome in young patients.

2. Space constraints imposed by editorial considerations prevented us from discussing the nuances of CBS in detail. But, we state quite clearly in the first sentence of the discussion that CBS occurs "in the setting of significant bilateral prechiasmal impairment". This visual impairment can be rather severe central vision loss, as in age related macular degeneration, or a combination of central vision loss with peripheral visual field loss as documented in our patients.

3. If our patients, including case 4, were not taking brimonidine tartrate eye drops we would have diagnosed them with CBS. Therefore, we feel justified in concluding that brimonidine tartrate precipitated the CBS in our patients, and we agree that this should be considered a potential side effect of this medication.

Dear Editor

We read, with interest the article 'Charles Bonnet Syndrome precipitated by Brimonidine Tartrate eye drops' published in July 2003 BJO. Interest in Charles-Bonnet syndrome (CBS) has escalated of late, highlighting the probable 15% [1] incidence of the condition in patients with significant visual impairment coupled with a clear sensorium.

The authors implied that CBS was induced in 4 patients by Brimonidine Tartrate (BT) on the basis of patient age and the instigation of BT therapy, with discontinuation resulting in eventual resolution of the hallucinations. Firstly, the diagnostic criteria proposed by Podell et al,[2] and Gold and Rabins [3] quite rightly made no reference for age being indicative of CBS, although incidence certainly increases with age. Schwartz [4] found that CBS also occurred in children following profound visual loss. This suggests that the high incidence in the elderly population is possible be attributable to the increased incidence of acquired visual loss occurring with age; therefore, age is not a criteria for diagnosis. Further, although the Snellen acuity of all 4 patients was reasonably good in at least one eye of each patient, it may be surmised that severe visual impairment may have been due to visual field loss secondary to glaucomatous damage. Although this is not clear from the article, the cause of visual impairment and bilaterality are important in the diagnosis of CBS. Indeed, bilateral advanced visual field defects induced by glaucoma and homonymous hemianopia have resulted in CBS.[5,6] A prevailing theory suggests sensory visual deprivation as an integral causative factor in CBS. Interestingly, and supportive of this theory, is that musical pseudohallucinations have been documented in cases of acquired deafness.[7] Sensory deprivation in the presence of a clear sensorium will necessary bilaterally to induce CBS, although no lower limit of Snellen visual acuity has been defined as a level for which CBS symptoms are stimulated. In the article case 4 seems to have sufficiently adequate visual function in the right eye to justify a definite misdiagnosis of CBS.

Secondly, as mentioned by the authors, alpha-2 agonists have been shown to cause systemic and neuropsychiatric phenomena.[8] As with any medication, the expectation would be resolution of induced symptoms, and as such we believe the hallucinations may easily be explained as a side effect of the medication. BT is a known lipophilic compound able to penetrate the blood-brain barrier. Through the accompanying package insert, neurological side effects such as depression and dizziness are well known. There is, therefore, little doubt that in the aged population in whom pharmacokinetics is often unpredictable, likelihood of greater systemic absorption and distribution may well lead to neuropsychiatric phenomena. Consequently, we believe that CBS was not the cause of the complex visual hallucinations experienced by these patients and may be attributed to a rarer side-effect of BT, which should now be included in the patient information leaflet.

References

(1) Menon GJ, Rahman I, Menon SJ, Dutton GN. Complex visual hallucinations in the visually impaired: the Charles Bonnet Syndrome. Surv of Ophthalmol 2003: 48;58-72 (Major Review)

(2) Gold K, Rabins PV: Isolated visual hallucinations and the Charles- Bonnet Syndrome: A review of the literature and presentation of six cases. Compr Psychiatry 1989; 30:90-98.

(3) Podoll K, Osterheider M, Noth J: Das Charles Bonnet Syndrom. Fortschr Neurol Psychiat 1989;57:43-60.

(4) Schwartz TL, Vahgei L: Charles Bonnet syndrome in children. J AAPOS 1998;2:310-3.

(5) Damas-Mora J, Skelton-Robinson M, Jenner FA: The Charles Bonnet Syndrome in perspective. Psychol Med 1982; 12:251-61.

(6) Dodd J, Heffernan A, Blake J: Visual hallucinations associated with Charles Bonnet Syndrome - an ever increasing diagnosis. Ir Med J 1999;92:344-345.

(7) Griffiths TD: Musical hallucinosis in acquired deafness: Phenomenology and brain substrate. Brain 2000;123:2065-2076.

(8) Kim DD, Bay G. A case of suspected Alphagan-induced Psychosis. Arch Ophthalmol 2000;118:1132-33.