Volume 207 - Issue 7
Clozapine-induced maculopathy
Authors: Heather G Mack and RC Andrew Symons
Med J Aust 2017; 207 (7): 316. || doi: 10.5694/mja17.00384
Published online: 2 October 2017
Published online: 2 October 2017
To the Editor:
We thank Tong and colleagues1 for their report on a patient with schizophrenia and clozapine-induced maculopathy, and for highlighting this under-recognised condition.
Both typical2 and atypical3 antipsychotic drugs have been reported to cause widespread retinopathy; more recently, there have been reports of rare cases of retinal damage localised to the macula (maculopathy) due to both typical4 and atypical1,5 antipsychotics. The classical hypothesis for widespread pigmentary retinopathy is that drugs are absorbed by melanin in the retinal pigment epithelium (RPE) and act as photosensitisers to damage the RPE. This results in loss of RPE support functions of overlying photoreceptors, which secondarily degenerate. An alternative hypothesis,2 supported by histological and animal studies, is that the problem begins in photoreceptors, with drug-induced blockade of retinal dopamine receptors followed by photoreceptor and subsequent RPE cell loss. Neuroleptic retinal drug toxicity typically involves pigment disruption in the RPE, but the dopamine hypothesis allows for broader combinations of RPE and/or photoreceptor damage. The reasons for the development of maculopathy in some patients, rather than a widespread retinopathy, are not known. This phenomenon is seen in other ocular drug toxicities, particularly hydroxychloroquine. Most drug-induced retinal toxicities are bilateral and symmetrical; asymmetrical cases have rarely been reported. The patient reported by Tong and colleagues is atypical with apparently unilateral macular changes.1
Significant differential diagnoses for unilateral macular pigment and photoreceptor changes include age-related and secondary to retinal conditions, such as central serous chorioretinopathy, inflammatory retinopathies and trauma. Maculopathy limited to the outer neuroretina may occur with the use of other drugs (eg, poppers maculopathy).6 Also, schizophrenia is known to cause illness-related retinal changes in the neuroretina but not in the RPE.7
We agree that patients taking psychotropic medications benefit from a multidisciplinary approach when ocular symptoms and signs develop.
Competing interests
No relevant disclosures.
References
- Tong JY, Pai A, Heydon P, Young SH. Clozapine-induced maculopathy. Med J Aust 2017; 206: 246.
- Richa S, Yazbek JC. Ocular adverse effects of common psychotropic agents: a review. CNS Drugs 2010; 24: 501-526.
- Faure C, Audo I, Zeitz C, Letessier JB, Robert MP. Aripiprazole-induced chorioretinopathy: multimodal imaging and electrophysiological features. Doc Ophthalmol 2015; 131: 35-41.
- Lee MS, Fern AI. Fluphenazine and its toxic maculopathy. Ophthalmic Res 2004; 36: 237-239.
- Borovik AM, Bosch MM, Watson SL. Ocular pigmentation associated with clozapine. Med J Aust 2009; 190: 210-211.
- Clemens CR, Alten F, Loos D, et al. Poppers maculopathy or retinopathy? Eye 2015; 29: 148-149.
- Ascaso FJ, Rodriguez-Jimenez R, Cabezón L, et al. Retinal nerve fiber layer and macular thickness in patients with schizophrenia: Influence of recent illness episodes. Psychiatry Res 2015; 229: 230-236.