Table 2.

Types and management of ocular surface adverse effects caused by novel anticancer drugs.

Agent	Malignancy	Ocular Surface Adverse Effects	Management
Immune checkpoint inhibitors
Ipilimumab Avelumab Durvalumab Nivolumab Pembrolizumab Atezolizumab Cemiplimab	Hodgkin lymphoma Colorectal cancer Gastric cancer Urothelial carcinoma Non-small-cell lung cancer Hepatocellular carcinoma Head and neck cancers	Dry eye Blepharitis Conjunctivitis Ulcerative keratitis Cicatrizing conjunctivitis Corneal transplant rejection Corneal perforation	Topical cyclosporine, artificial tears, punctal occlusion Eyelid scrubs, warm compressions, systemic antibiotics for severe cases Resolve quickly on its own. Careful slit lamp examination to exclude infectious and allergic etiologies Bandage contact lenses, corneal glue, topical autologous serum and optimizing the ocular surface with artificial tears and punctal occlusion. Depending on the severity and the patient’s response to ocular therapy, stopping anticancer therapy should be considered, as well as surgery (penetrating keratoplasty)
Epidermal Growth Factor Receptor Inhibitors
Gefitinib Erlotinib Afatinib Osimertinib Dacomitinib Necitumumab Cetuximab Panitumumab	Non-small-cell lung cancer Pancreatic cancer Colorectal cancer Head and neck cancers	Conjunctivitis Dry eye Superficial punctate keratopathy Corneal ulcer Keratitis Keratouveitis Corneal edema Vortex keratopathy Eyelid rash Trichomegaly	Resolve quickly on its own. Careful slit lamp examination to exclude infectious and allergic etiologies Manage according to the Tear Film Ocular Surface Dry Eye Workshop II guidelines Ocular lubricant, topical antibiotic, bandage contact lens, considering discontinuing treatment or reducing dosage Eyelid hygiene
Fibroblast Growth Factor Receptor Inhibitors
Erdafitinib	Urothelial cancer	Keratitis Corneal thinning	Ocular lubricant and topical autologous serum, considering discontinuing treatment or reducing dosage
Human Epidermal Growth Factor 2 Inhibitors
Trastuzumab Pertuzumab	Breast cancer	Conjunctivitis Infectious crystalline keratopathy Corneal ulcer Increased lacrimation	Resolve quickly on its own. Careful slit lamp examination to exclude infectious and allergic etiologies. Autologous serum and topical antibiotics, in addition to drug discontinuation.
Mitogen-activated protein kinase inhibitors
Trametinib Cobinetimib Binimetinib	Melanoma Colorectal cancer Non-small cell lung cancer	Dry eye	Manage according to the Tear Film Ocular Surface Dry Eye Workshop II guidelines
BRAF Inhibitors
Vemurafenib Dabrafenib Encorafenib	Melanoma Non-small cell lung cancer Thyroid cancer Colorectal cancer	Dry eye Conjunctivitis Blepharitis	Manage according to the Tear Film Ocular Surface Dry Eye Workshop II guidelines Resolve quickly on its own. Careful slit lamp examination to exclude infectious and allergic etiologies Eyelid scrubs, warm compressions, systemic antibiotics for severe cases
Selective Estrogen Receptor Modulator
Tamoxifen Raloxifene Toremifene	Breast cancer	Keratopathy Dry eye	Only observation. Temporary drug suspension or discontinuation could be considered in symptomatic cases Manage according to the Tear Film Ocular Surface Dry Eye Workshop II guidelines
Aromatase inhibitors
Anastrozole Letrozole Exemestane	Breast cancer	Blepharitis Meibomian gland dysfunction Dry eye Superficial punctate keratitis Conjunctival injection	Eyelid scrubs, warm compressions, systemic antibiotics for severe cases Manage according to the Tear Film Ocular Surface Dry Eye Workshop II guidelines Only observation
Breakpoint cluster region–Abelson oncogene inhibitors
Imatinib Nilotinib	Chronic myeloid leukemia	Conjunctivitis Keratoconjunctivitis Dry eye	Resolve quickly on its own or with the use of topical therapy. Careful slit lamp examination to exclude infectious and allergic etiologies Manage according to the Tear Film Ocular Surface Dry Eye Workshop II guidelines
Fms-like tyrosine kinase 3 inhibitors
Gilteritinib	Acute myeloid leukemia	Dry eye	Manage according to the Tear Film Ocular Surface Dry Eye Workshop II guidelines
Bruton’s tyrosine kinase inhibitors
Ibrutinib	B-cell malignancies	Dry eye	Manage according to the Tear Film Ocular Surface Dry Eye Workshop II guidelines
Anaplastic lymphoma kinase inhibitors
Crizotinib	Non-small cell lung cancer	Conjunctival chemosis	Drug discontinuation
Vascular endothelial growth factor receptor inhibitors
Pazopanib Vandetanib	Renal cancer Sarcoma Non-small cell lung cancer Thyroid cancer	Dry eye Keratitis Vortex keratopathy	Manage according to the Tear Film Ocular Surface Dry Eye Workshop II guidelines Drug discontinuation
Proteasome inhibitors
Bortezomib Carfilzomib Ixazomib	Multiple myeloma	Chalazia Blepharitis Conjunctivitis Dry eye	Eyelid scrubs, warm compressions, systemic antibiotics for severe cases Resolve quickly on its own. Careful slit lamp examination to exclude infectious and allergic etiologies Manage according to the Tear Film Ocular Surface Dry Eye Workshop II guidelines
Antibody–Drug Conjugates
Trastuzumab deruxtecan Belantamab mafodotin Trastuzumab emtansine Enfortumab vedotin Mirvetuximab soravtansine	Breast cancer Multiple myeloma Breast cancer Urothelial cancer Ovarian cancer	Dry eye Dry eye Keratopathy Dry eye Dry eye Keratopathy	Manage according to the Tear Film Ocular Surface Dry Eye Workshop II guidelines Avoiding contact lenses, applying cold compressions for symptomatic alleviation, and using preservative-free artificial tears at least four times a day Hyaluronic acid, autologous serum, or observation are all possible, without changing anticancer therapy and dosage Artificial tears and topical corticosteroids if necessary Using lubricating eye drops every day and occasionally using corticosteroid eye drops. In addition, patients should also have an eye examination at baseline, every other cycle for the first eight cycles of treatment, and dose modifications should also be considered if clinically indicated