3.3 Retinal injury
The incidence of retinal injury is rare, which appears mainly as macular edema. The primal symptom of macular edema caused by taxane is impaired vision acuity. Kaya et al. [7] reported 202 patients who received taxane-based therapy due to treatment of various cancer, taxane-related cystoid macular edema (CME) was detected only in one patient on paclitaxel. Generally, the proportion of taxane-related maculopathy was 0.5% (1/202) of all patients in the taxane group. However, this particular macular edema, which has the characteristics of not presenting the classic angiographic findings link to other macular edema (eg, diabetic macular edema (DME), macular edema secondary to retinal vein occlusion (RVO-ME) or uveitis) in a straightforward manner. In the macular edema caused by tanxane, optical coherence tomography (OCT) showed increased thickness of macular fovea, and fundus fluorescence angiography (FFA) examination did not reveal any source of leakage. In addition, macular edema will disappear spontaneously after drug withdrawal. The pathological mechanisms for this particular type of macular edema are still unclear of which there have no histopathological studies but only case reports yet. However, there are different speculations about the pathogenesis of taxane-induced macular edema. On the one hand, some scholars believe that such drug-induced macular edema may be caused by cytotoxicity caused by paclitaxel which inhibits intracellular microtubule recombination [22]. On the other hand, others, such as Nomi, consider that the mechanisms could be internal accumulation of intracellular fluid and minimal impairment of the blood retinal barrier (BRB) [8]. Another theory, which would also explain the angiographic findings, would be that the edema was due to an accumulation of fluid in the intracellular space. At the same time, other scholars interpreted the imaging results of no leakage or minimal leakage as Müller cells cytotoxicity. Because Müller cells are responsible for maintaining the nerve sensory osmotic gradient in the retina, and their dysfunction leads to the accumulation of intracellular fluid [1]. Besides, it has also been found that the electroretinogram (EGR) b wave parameters are normal and the Arden ratio is low, suggesting RPE involvement [23].
Meanwhile, through experiments on animals, Kuwata et al [21] found that ocular toxicity of different doses of paclitaxel to newborn SD rats of different ages also showed that retinal dysplasia occurred after intraperitoneal injection of 4 or 8 mg/kg paclitaxel in 0-day-old SD rats. This suggested that the ocular side effects of paclitaxel were related to the duration and concentration of the drug. In our current study, we found in vivo that the same mice were injected with the drug for different time, and the visual electrophysiological examination showed that the time of receiving the drug was longer and the eye damage was more serious. In vitro experiments, we detected the survival ability of RPE cells and Müller cells, and found that the survival ability of cells receiving the same concentration of drug stimulation for a longer time was worse. Those who received higher doses of the drug for the same time had poorer cell survival. (unpublished data).