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Milluzzo et al. Metab Target Organ Damage 2024;4:5 https://dx.doi.org/10.20517/mtod.2023.43 Page 3 of 14

RETINAL EFFECTS OF THE DIFFERENT ANTICANCER DRUG CLASSES
Anti-oestrogen
Antioestrogen is used in the management of breast cancer. Ocular side effects of hormone therapy are less
frequent than other organ toxicity, although their incidence is probably underestimated .
[19]

In particular, tamoxifen is an oral selective oestrogen receptor modulator used in the treatment of hormone
receptor-positive breast cancer. Tamoxifen binds competitively to the cytoplasmic oestrogen receptors,
[19]
entering the nucleus and inhibiting DNA synthesis, and its use is related to retinal thromboembolism .
Tamoxifen penetrates the choriocapillary barrier and induces glycosaminoglycan deposition in the
[18]
plexiform layers of the retina nerve fiber, determining axonal injury .

A retrospective analysis of “The International Breast Cancer Study” evaluated, in a large number of subjects,
the ocular toxicity related to adjuvant hormonal treatment (tamoxifen or toramifen) for breast cancer
[20]
[Table 1]. The authors reported the occurrence of retinal adverse events during hormone therapy in about
1% of the cohort, although other cohorts observed a 6% incidence . The main retinal alterations include
[21]
refractile yellowish deposits in the area surrounding macula, nerve, and plexiform layers. In the case of
extensive deposits, macular oedema and visual acuity reduction occurred. These features regressed after
tamoxifen withdrawal, although retinal deposits were permanent. The cumulative dosage of tamoxifen and
duration of treatment could predict the risk for retinal damage, with the deposits occurring as the
cumulative dosage approaches 100 g .
[19]

Few data are available on the risk for onset or progression of retinopathy in diabetic subjects treated with
tamoxifen [Table 1]. Moussa and colleagues observed the onset of superficial retinal haemorrhages,
exudates and macular oedema, in a 52-year-old woman who presented with blurry vision, a history of well-
controlled T2D, and breast cancer previously treated with tamoxifen .
[22]

Similar retinal alterations were reported by Bommireddy and colleagues in a 52-year-old, non-diabetic
woman who, at the time of visual impairment, was taking for about 5 years, 20 mg/day of tamoxifen to treat
a grade 2, invasive lobular breast cancer . Although the incidence of ocular toxicity during hormonal
[23]
therapy is low, subjects treated with tamoxifen should be alerted of this possible side effect to promptly
ruling out an ophthalmic evaluation in case of visual injury .
[20]

Androgen deprivation therapy
Anti-androgen drugs represent the standard of care for the treatment of prostate cancer both in adjuvant
[24]
therapy and for the treatment of recurrence or biochemical failure .
Gonadotropin-releasing hormone agonists, as well as steroidal (cyproterone acetate) and nonsteroidal anti-
androgens (flutamide, bicalutamide, and nilutamide), have a detrimental effect on body weight, fat
composition, and insulin sensitivity, determining in diabetic subjects a worsening of glucose control [4,25,26] .
The risk for DR is tightly related to the level of glucose control and insulin resistance; nevertheless, very
limited evidence is available on the influence of anti-androgen on retinal health. In a large retrospective
cohort observing 5,336 men newly diagnosed with localised prostate cancer and affected by pre-existing
T2D, no significant increased risk for DR was reported in the group treated with androgen deprivation
therapy. These men were treated with gonadotropin hormone-releasing hormone (GnRH) analogues
(leuprolide, goserelin, or triporelin) or GnRH antagonists (abarelix or degarelix), with or without an oral
anti-androgen (flutamide, bicalutamide, or nilutamide) . Recently, we retrospectively evaluated the retinal
[24]
short-term effects of cancer drugs in 168 patients with different cancer types (mean age 55.7 years) and