Markedly increased ocular side effect causing severe vision deterioration after chemotherapy using new or investigational epidermal or fibroblast growth factor receptor inhibitors

Table 5 Known ocular side effects of prior chemotherapy agents before EGFR and FGFR inhibitor therapy

Prior chemotherpy agents before study drugs	Mechanism [24,25,26,27,28,29,30,31,32]	Known ocular side effects
Afatinib	EGFR-inhibitor	Anterior uveitis [32]
Capecitabine	Antimetabolite/pyrimidine analog	dry eye, lacrimation [24],
Cisplatin	Alkylating agent/platinum	Blurred vision, retinotoxicity (retinal ischaemia and neovascularization), optic neuropathy [33]
Doxorubicin	anthracyline drug	conjunctivitis (m/c), periorbital edema, lacrimation, blepharospasm, keratitis, and decreased visual acuity [34]
Everolimus	mTOR inhibitor	posterior reversible encephalopathy syndrome,bilateral optic neuropathy [35]
Geftinib	EGFR-inhibitor	Dry eye, corneal ulcer [36, 37]
Gemcitabine	antimetabolite agent	uveal effusion and outer retinal disruption or Purtscher-like retinopathy with combination of docetaxel [25, 38]
Irinotecan	topoisomerase I inhibitor	None [39], none in combination regimen with 5-fluorouracil, oxaliplatin and bevacizumab [40]
Oxaliplatin	platinum	dry eye, lacrimation, conjunctivitis, damage of the retinal pigment epithelium and the optic nerve, visual field defect [30, 41]
Paclitaxel	Antimicrotubule agent	epiphora, eye pain, conjunctivitis, blepharitis, blurred vision [24, 42]
Pemetrexed	Antimetabolite /antifolate	AION [1], eyelid edema [24, 43]
Ramucirumab	monoclonal Ab of VEGFR-2	none [28]
Sorafenib	anti-VEGF agent	blurred vision, periocular edema, retinal detachment, ptosis, optic neuropathy, macular edema [27, 44]
Temozolomide	alkylating/methylating agent	blurred vision with concurrent radiation therapy [45].

AION Anterior ischemic optic neuropathy, VEGF Vascular endothelial growth factor, Ab Antibody, VEGFR Vascular endothelial growth factor receptor, mTOR mammalian target of rapamycin

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