Page 65 - Read Online

Milluzzo et al. Metab Target Organ Damage 2024;4:5 https://dx.doi.org/10.20517/mtod.2023.43 Page 7 of 14

The combined treatment with alkylating agents and taxanes is common in various solid malignancies. Some
reports described the different degrees of retinal toxicity due to the contemporary use of carboplatin and
paclitaxel. Matsuyama and colleagues described the case of a 59-year-old man with good diabetes control
(glycated haemoglobin 5.8%) and treated with both paclitaxel and carboplatin for a non-small cell lung
cancer, who experienced severe visual loss due to a large number of bilateral soft exudates, retinal ischaemia,
and haemorrhages. This retinal injury was resistant to laser photocoagulation and disappeared after
stopping cancer treatment . The case of paclitaxel and carboplatin retinal damage was described in a non-
[28]
diabetic 70-year-old female affected by cervical cancer: bilateral mild decreased vision appeared four weeks
after initiating chemotherapy, including 4 cycles of paclitaxel (175 mg/m ) and carboplatin. Retinal
2
examination showed an early ischemic retinopathy and cotton wool spots. Both symptoms and retinopathy
[29]
signs disappeared after drugs cessation .
Several mechanisms, not fully clarified, have been proposed to explain how alkylating agents induce retinal
ischemia. In particular, thrombosis could be related to the platelet activation mediated by phospholipase A2
increased activity .
[29]
Paclitaxel was reported to determine symptomatic cystoid macular oedema in a 49-year-old woman with
ovarian cancer, probably due to its detrimental effect on the blood-retinal barrier: oedema appeared after
more than one year since paclitaxel treatment (cumulative dose of 1,680 mg) and regressed with drug’s
[30]
discontinuation . Chelala and colleagues found an increased central macular thickness, without significant
macular oedema nor reduced visual loss, in 25 subjects affected by different solid cancers treated with
[31]
various protocols (4EC-4T, 3FEC/3T, or 4TC) including paclitaxel or docetaxel .
Few reports described retinal damage in paediatric subjects treated with alkylating agents in combination
[32]
with topoisomerase inhibitors, in particular etoposide [Table 1]. Hilliard and colleagues reported two
cases of new-onset blurry vision after 4 months after cisplatin (40 mg/m /day) and etoposide (100 mg/m /
2
2
day) initiation. Fundus examination showed a bilateral mild diffuse optic nerve pallor and retinal granular
pigmentation . The authors explained the ocular toxicity by the reduced renal clearance of platinum
[32]
and increased plasma level.
Kwan and colleagues described the case of cisplatin-related retinal toxicity in a 31-year-old male after ten
2
weeks of treatment (20 mg/m /day, cumulative dose 528 mg) for testicular cancer : fundus oculi and
[33]
fluorescein angiographic examinations revealed some cotton wool spots and scattered intraretinal
haemorrhages near the macula at both eyes and retinal neovascularization at the left eye. Visual acuity did
not improve after laser photocoagulation and the cessation of the chemotherapy .
[33]
The multidrug chemotherapy regimens usually used for cancer treatment make it difficult to explore the
exact role of each drug on the onset of retinal adverse events. In this regard, an interesting report described
the case of a 58-year-old diabetic man suffering from bladder cancer who developed, after 4 months of
treatment with gemcitabine - antimetabolites molecule - and alkylating agents, microaneurysms, capillary
leakage, cotton wool spots, haemorrhages, thickening of the macula, and mild retinal oedema in both
eyes . The treatment discontinuation led to an improvement in the retinal injury. However, the cancer
[34]
relapsed, gemcitabine was reintroduced in monotherapy, and retinopathy appeared again after a month.
The clinical improvement observed after gemcitabine withdrawal and the retinopathy relapse after the
second exposure to the drug seem to indicate the causal role of gemcitabine in the onset of retinopathy .
[34]