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).