Ocular side effects of biological agents in oncology: what should the clinician be aware of?

Abstract

During the last 20 years, biologicals have become increasingly relevant in oncologic therapy. Depending on the medication used, there are different profiles of ocular side effects. Although these can be present in up to 70% of patients, they are generally underreported in the literature. Therefore, the pathophysiological details of their development are often poorly understood. Herein we attempt to identify groups of biologicals to which a specific side effect profile can be assigned. We also tried to capture all relevant side effects and therefore conducted several database investigation including Medline, Cochrane library, and the drugs section of the US Food and Drug Administration (FDA), using the following search strings: “name of biological agent (both generic and commercial names)” AND “eye” OR “ocular”. If we found a side effect that has been associated with a drug, we researched Medline using the following search string: “name of biological agent” (both generic and commercial names) AND “term for the specific side effect”. Due to the wealth of material we report only the drugs that are approved by the FDA.

Ocular Toxicity of Tyrosine Kinase Inhibitors

“…The complex functioning of the eye combines the neural network system with blood vessels, muscles, and skin that can be affected by targeted agents, often with different receptor-specific patterns that do not occur in this form elsewhere in the body (Hager & Seitz, 2014). Table 1 lists common TKIs, as well as their targets, specific cancers, and associated ocular effects.…”

“…Drugs that target these receptors can cause periorbital edema and epiphora in as many as 70% of patients (Fraunfelder, Solomon, Druker, Esmaeli, & Kuyl, 2004). The edema usually occurs from five to eight weeks after initiation of treatment but can occur as early as within 24 hours or as late as after one year, depending on the dose (Hager & Seitz, 2014). Imatinib (Gleevec ® ) may also cause subconjunctival hemorrhages, thought to be related to targeting c-kit–positive mast cells on the conjunctiva (Kheir et al, 2014).…”

New-onset uveitis during CTLA-4 blockade therapy with ipilimumab in metastatic melanoma patient

“…13 Thus, a cross reaction of anti-gp100 T cells with the iris pigment epithelium or a cross reaction because of a reinforced T-cell response were considered potential causes for the development of this type of uveitis. 12 To our knowledge, this is the first report of autoimmune uveitis in patients treated with ipilimumab only. This means that, although the previous use of vaccines that contain gp100 peptides could facilitate its occurrence, autoimmune uveitis may be considered an important adverse event related to the use of anti-CTLA-4 mAb even in the absence of previous therapy with vaccines that contain gp100 peptides.…”

“…Since then, there have been rare reports on the development of bilateral anterior uveitis under ipilimumab therapy; but until now all patients who experienced development of uveitis on ipilimumab were previously subcutaneously treated with vaccines that contain gp100 peptides. 12 Melanocytespecific gp100 is a protein expressed by melanoma cells. Vaccination with gp100 peptides is intended to suppress the development of melanoma.…”

Management and Supportive Care of Patients Undergoing Immunotherapy

“…Besides, from the direct toxicity of immunotherapy agents, the eye can also indirectly be afected via other immune-related adverse endocrinopathies such as hyperthyroidism form autoimmune thyroiditis [30,43]. There have been case reports of Grave's opthalmopathy with symptoms and signs of proptosis associated with swelling of extraocular muscles and xeropthalmia [30,42,44]. Ophthalmological side efects include episcleritis, conjunctivitis, and uveitis [3].…”