As more targeted cancer treatments are developed and cancer death rates continue to decline, “many people will be maintained long-term on cancer therapy—and these are patients who could walk into your office with a retinal problem,” said Jasmine H. Francis, MD.
At Retina Subspecialty Day on Saturday, Dr. Francis outlined retinal toxicities related to several newer cancer medications:
Small molecule inhibitors. Dr. Francis covered ALK, BCR-ABL, BRAF, and MAPK inhibitors.
- ALK inhibitors are mainly used to treat lung cancer. “Upward of 70% of patients will describe a photopsia” that presents as a “trail of light,” Dr. Francis said. This primarily occurs in patients who are on crizotinib. “It was thought to be due to an abnormality in the central nervous system but is now thought to be due to disturbed signaling of the retinal ganglion layer,” Dr. Francis said. The condition is mild and self-resolving.
- BCR-ABL inhibitors are primarily used to treat gastrointestinal stromal tumors and chronic myeloid leukemia. “The majority of these patients will develop some degree of orbital edema,” Dr. Francis said. “Many will have subconjunctival hemorrhages; rarely, patients may develop cystoid macular edema (CME).” The mechanism underlying these retinal findings is unknown. Fortunately, “These findings are reversible with drug reduction or cessation, and there are some reports of macular edema resolution with anti-VEGF or steroid injections.”
- BRAF inhibitors are used to treat thyroid cancer but also may be given to patients with melanoma and some leukemias and lymphomas. “Approximately 5% of patients will develop a bilateral anterior nongranulomatous uveitis, sometimes in association with a CME panuveitis,” Dr. Francis said. The underlying mechanism is thought to be related to an inflammatory response against apoptotic tumor cells, she said. Patients typically respond to steroids, with or without cessation of the BRAF inhibitor.
- MAPK inhibitors are primarily used to treat gastrointestinal stromal tumors, urologic and ovarian cancers, and melanoma. The main retinal findings are retinopathy in 15% of patients and, rarely, central retinal vein occlusion (CRVO) in 0.5%. “The mechanism underlying the retinopathy is unknown, and the condition is intermittent, temporary, and reversible, even when patients remain on the drug,” Dr. Francis said. The occurrence of CRVO is thought to be driven by oxidative stress. Visual rehabilitation is possible, and anti-VEGF injections may be given, she added.
Immune checkpoint inhibitors. These include CTLA, PD-1, and PD-L1 inhibitors. The drugs are primarily prescribed to patients with lung cancer and melanoma—although, as Dr. Francis pointed out, “these are increasingly being used for a whole host of different cancers.”
The drugs potentiate the T-lymphocyte response throughout the body, killing cancer cells but also creating inflammation elsewhere. A variety of posterior segment inflammatory conditions have been reported with use of the drugs. Dr. Francis highlighted myriad potential findings, including CME, uveal effusion, retinal vasculitis, and uveitis.
Of note, the findings “may be incomplete, involving just the eyes, or complete, involving neurological and dermatological findings,” she said. “The take-home message here is that immune checkpoint inhibitors can inflame any layer of the eye—literally any layer, which can make for a very hot eye.”
The inflammation typically responds to steroids, although drug cessation may be needed. In some cases, IV immunoglobulins or plasmapheresis is required. —Jean Shaw
Financial disclosures: Dr. Francis: None.