Tyrosine-kinase inhibitors, used to treat a form of leukemia, can induce fluid retention and periorbital edema by decreasing interstitial pressure and increasing transcapillary fluid transport. Conceivably, the mechanism through which edema occurs may extend to the optic nerve tissue, the authors speculate, leading to optic neuritis. Photo: Nate Lighthizer, OD. Click image to enlarge.

While modern targeted cancer therapies have led to a significant improvement in patient outcomes, they can cause rare neuro-ophthalmic complications. A recent study sought to better understand the complications associated with these drugs and their management.

This review included drugs targeting specific molecules involved in the cancer disease process, such as tyrosine kinase inhibitors, immune checkpoint inhibitors, proteasome inhibitors, antibody–drug conjugates and selective inhibitors of nuclear export.

Researchers searched PubMed, EMBASE and Web of Science using the generic names of each drug and keywords of neuro-ophthalmic conditions. They also reviewed the FDA prescribing information for each drug.

Several classes of targeted anti-cancer drugs associated with neuro-ophthalmic adverse effects were identified. For instance, anti-VEGF therapies can lead to posterior reversible encephalopathy syndrome (PRES). This condition, which typically presents with visual loss, can be fatal without prompt interventions.

The study authors also reported that immune checkpoint inhibitors can cause a number of immune-related adverse events, including optic neuritis, ischemic optic neuropathy, PRES and myasthenia gravis. Drugs that inhibit BCR-ABL1, VEGF, ALK and proteasomes have been associated with optic nerve disorders.

While treatments such as corticosteroids can address many of these complications, drug discontinuation is usually required, according to the study authors, who noted that this has important implications for a patient’s cancer treatment and prognosis, which is why multi-disciplinary discussion is critical.

“It is of key importance that ocular symptoms are promptly referred and investigated, and that ophthalmologists are aware of the possibility of neuro-ophthalmic complications in patients with a history of treatment with targeted anti-cancer drugs,” they wrote in their paper on the study. “Furthermore, certain patients may be at higher risk of developing neuro-ophthalmic complications, such as those with a history of neuro-ophthalmic or autoimmune conditions taking immune checkpoint inhibitors, and this should be taken into account by oncologists when discussing treatment selection.”