Toxic effects of phenothiazines on the eye

Summary

Publications about the retinotoxic action of phenothiazine derivatives led the author to undertake an ophthalmological investigation in two psychiatric hospitals in The Netherlands.

The pharmacological actions of phenothiazine preparations are listed and a survey of the phenothiazine derivatives which are at present in use is given.

Some retinotoxic substances are discussed and a survey is given of the literature on the ocular complications of phenothiazine therapy.

The eyes of 561 patients were examined, of whom 541 are included in this study. 343 of these patients (63.4 %) were found to have retinopathy. The correlation between the retinopathy and the total dose of phenothiazine preparations taken, and between the retinopathy and the duration of treatment, was highly significant. The correlation between the retinopathy and the average daily dose taken was significant.

The retinopathy was associated with a reduced standing potential of the eye, as determined by electro-oculography. It was possibly responsible for diminished visual acuity in some cases, and for an abnormally large proportion of protans in the group of patients with colour defects.

It was not possible to ascribe a more severe retinotoxic action to one or more specific phenothiazine derivatives than to others.

In the author's opinion regular examination of the eyes of patients who are being treated with phenothiazine preparations in high dosage and/or for a long period of time is indicated.

Résumé

Après avoir pris connaissance de l'effet rétinotoxique des dérivés de la phé-nothiazine, l'auteur a entrepris des recherches dans deux hÔpitaux psychiatriques des Pays Bas.

L'action pharmacologique des préparations de phénothiazine est rappelée et les dérivés actuellement utilisés sont passés en revue.

Quelques substances rétinotoxiques sont discutées et la littérature concernant les complications oculaires observées au cours de traitements à la phénothiazine est commentée.

Les yeux de 561 patients ont été examinés. 541 d'entre eux entrent dans cette étude. Chez 343 de ces malades (63,4%) on a observé une rétinopathie. Les corrélations entre la rétinopathie d'une part, la dose totale de phénothiazine ou la durée du traitement d'autre part, étaient hautement significatives. La corrélation entre la rétinopathie et la dose moyenne journalière était significative.

La rétinopathie est associée à une réduction du potentiel continu (standing potential) qui est déterminé par l'électro-oculographie. Elle était peut-être aussi responsable de la diminution de l'acuité visuelle constatée dans un certain nombre de cas, et de la proportion anormalement élevée de protanopes dans le groupe de malades atteints d'anomalies du sens chromatique.

Il était impossible d'attribuer à certains dérivés de la phenothiazine un effet rétinotoxique plus fort qu'à d'autres.

Un examen oculistique régulier de malades qui emploient des préparations de phenothiazine pendant un temps plus long et/ou en grandes doses, a été indiqué d'après l'auteur.

Zusammenfassung

Nach Kenntnisnahme der Veröffentlichungen über den retinotoxischen Einflu\ der Phenothiazinderivate hat der Verfasser eine Untersuchungsreihe in zwei psychiatrischen Kliniken der Niederlande unternommen.

Die pharmakologischen Eigenschaften von Phenothiazinpräparaten werden aufgezählt und die heute gebräuchlichen Phenothiazinderivate im Einzelnen besprochen.

Einige retinotoxische Substanzen werden diskutiert und es wird über die am Auge beobachteten Komplikationen der Phenothiazintherapie referiert.

Die Augen von 561 Patienten wurden untersucht. 541 davon wurden in dieser Reihe berücksichtigt. Bei 343 von diesen Patienten (63,4 %) wurde eine Retinopathie festgestellt. Die Korrelationen zwischen der Retinopathie einerseits, der Gesamtdosis des verabreichten Phenothiazins oder der Behandlungsdauer andererseits waren in hohem Maβe signifikant. Die Korrelation zwischen Retinopathie und mittlerer Tagesdosis war signifikant.

Die Retinopathie ist mit einer Herabsetzung des elektro-okulographisch gemessenen Ruhepotentials (standing potential) verbunden. Sie ist möglicherweise auch verantwortlich für die Sehkraftverminderung, die in einer gewissen Zahl von Fällen festgestellt wurde, und ebenso für den abnorm hohen Prozentsatz von Protanopen, der in der Gruppe der Patienten mit Farbsinnstörungen entdeckt wurde.

Es war unmöglich bestimmter Phenothiazinderivate eine stärkere retinotoxische Wirkung zuzuschreiben als andere.

Regelmäβige augenheilkundige Untersuchung von Patienten, die längere Zeit oder/und höhere Dosen Phenothiazinpräparaten einnehmen ist nach der Meinung des Verfassers notwendig.

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Boet, D.J. Toxic effects of phenothiazines on the eye. Doc Ophthalmol 28, 1–69 (1970). https://doi.org/10.1007/BF00153873

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Keywords

  • Retina
  • Visual Acuity
  • Chlorpromazine
  • Phenothiazine
  • Dark Adaptation