Topiramate and the retina: an abridged classification

Abstract

Editor:We read with great interest the recent paper by Kumar and colleagues 1 describing two cases of topiramate (TPM)-induced cilio-choroidal effusion syndrome (TiCCES) with retinal complications. In a recent systematic review of 74 available studies, we provided a classification for TPM-induced visual side-effects, 2 and herein would like to draw the kind attention of the reader toward the specific effects of TPM on the retina.As a definition, TiCCES is the spectrum of signs and symptoms ranging from transient 'topiramate-induced myopic shift' to bilateral 'topiramate-induced angleclosure glaucoma'. 2 The two interesting cases presented by the authors 1 necessitate highlighting the notion that TiCCES may accompany retinal complications due to the process of choroidal effusion throughout the posterior segment. As postulated by Guier 3 during the process of TiCCES, choroidal thickening and the resulting decrease in the area of Bruch's membrane/retinal pigment epithelium can cause retinal redundancy and consequent retinal folds or striae. This complication may even occur more severely, for example, the condition we described in our case where topiramate-induced massive bilateral choroidal effusion resulted in elevation of the retina. 4 Hence, the process of topiramate-induced ciliochoroidal effusion per se can be identified as an intermediating component between use of TPM and retinal complications. The nature of TiCCES is supposed to be related to idiosyncratic reactions presented during the first two weeks of drug initiation or dose doubling. 2,[5][6][7] This underlines the important point that TiCCES-related retinal side effects usually occur by transient exposure to low doses of the drug. In the literature, there are four cases that describe TiCCES-related retinal striae within one to 14 days (median of six days) of taking the drug at doses of 25 to 100 mg/day (median 50). 2Of note, this figure is similar to the characteristics of the overall TiCCES cases which we reviewed. Moreover, the spectrum of retinal effects of TPM expands to its possible direct effects on the histopathology and function of retinal cells and in particular, retinal ganglion cells.8 There are some clinical and experimental studies exploring the features and mechanisms of the direct effects of TPM on the retina. 2,7Existing literature lacks a convincing consensus on this subject; 8 however, three cases of TPM-related maculopathy and one with visual field defects provide objective evidence in support of direct adverse effects of TPM on the retina.2 These cases developed such conditions within two to 156 weeks (median 10 weeks) of taking the drug at doses of 125 to 400 mg/day (median 150 mg/day). These effects are not seemingly associated with the idiosyncratic process of TiCCES and occur following repeated exposure to TPM with probably higher doses than reported in TiCCES (median dose in 44 previous TiCCES cases was 50 mg/day).2 As a conclusion, we suggest classifying retinal effects of topiramate into two categories; First, acute complica...