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Page 6 of 14 Milluzzo et al. Metab Target Organ Damage 2024;4:5 https://dx.doi.org/10.20517/mtod.2023.43

Sorafenib Registry multicentre - 15% No Retinal haemorrhages Retinal signs disappeared after drug cessation [46]
international study Retinal detacòò
Sunitinib
4ùhments
Macular oedema
FGFR inhib
Infigratinib Multicentre, open-label, 17% Not indicated Chorioretinopathy - [47]
single-arm, phase 2 study Subretinal fluid
Serious retinal detachment.
AZD4547 Open-label, single-arm 50% Not indicated Subretinal fluid Subretinal fluid did not require any dose [48]
phase 2 study interruptions or reductions, and disappeared
after the last dose.
ICIs
Ipilimumab Case report of a 70-yo Cutaneous melanoma - No Serious retinal detachments After 6 weeks of ipilimumab withdrawal and [51]
woman Subretinal fluid glucocorticoid therapy, the retinal sign
(USA) disappeared.
Nivolumab Case report of a 64-yo NSCLC - No Narrowing of the retinal vessels Resolution after nivolumab discontinuation [52]
woman Retinal thinning and glucocorticoid treatment
(USA) Vitreous detachment
HER2 inhib
Trastuzumab Case report of a 50-yo Breast - No Retinal hard exudates Resolution after trastuzumab discontinuation [54]
woman Retinal haemorrhages
(France) Macular oedema
RAE: retinal adverse events; yo: years old; Alkyl: alkylating; NPDR: non-proliferant diabetic retinopathy; Topo: topoisomerase; Inhib: inhibitors; PDR: proliferant diabetic retinopathy; 5-FU: 5 fluorouracil; NSCLC: non-
small cells lung cancer; MAPK: mitogen-activated protein kinase; GIST: gastro-intestinal stromal tumour; VEGF: vascular endothelial growth factor; FGFR2: fibroblast growth factor receptor 2; ICIs: immune check
point inhibitors; HER2: human epidermal growth factor receptor 2.

previously diagnosed T2D (mean diabetes duration 9.3 years) [10,15] . In the subgroups of subjects (6% of the study cohort) treated for prostate cancer with anti-
androgens, we did not observe an increased risk for short-term adverse retinal outcomes [10,15] . Further prospective, larger studies are necessary to better
investigate these findings.

Classical cytolytic chemotherapy
Alkylating agents, anti-microtubule agents, antimetabolites, and topoisomerase inhibitors are currently used for the treatment of many cancers and could be
[27]
associated with various degrees of hyperglycaemia in patients previously not affected by diabetes . A toxic effect of these drugs on retinal tissue has been
occasionally observed in subjects with and without diabetes mellitus [Table 1]. In a real-world retrospective study including cancer patients also affected by
T2D for an average of 9 years, the use of alkylating agents and topoisomerase inhibitors was related to a seven- and nine-fold increase, respectively, of short-
term retinal worsening . This risk was more pronounced in obese subjects.
[15]