Ocular manifestations of Cancer drugs
Antibody drug conjugates (ADC)
Antibody drug conjugates (ADCs) are innovative cancer therapies that combine the specificity of monoclonal antibodies with the cytotoxic potency of chemotherapeutic drugs, targeting cancer cells more precisely. However, the use of ADCs may be associated with ocular side effects, ranging from mild symptoms such as blurred vision to more severe complications like retinal toxicity, highlighting the need for careful monitoring and management in clinical practice.
Mechanism of action:
ADC binds to receptor on target cell
ADC is internalized into endosome
Toxin is cleaved from the chemical linker
Toxin is released
Cell death
Possible theories on how this class of drugs affects ocular health:
Inappropriate binding of the antibody to an off-target side leads to the drug going where its not supposed to and killing the cell
Unstable linker
Highly toxic payload (most likely theory)
Ocular Side Effects
Example of MECs
MECS (micro cyst-like epithelial changes)
ADC enters corneal cell —> cell apoptosis —> MEC visualized in cornea
Begins peripheral and moves central as the corneal cell goes through its life cycle
Refractive Error Fluctuations
Largest shift is myopic in nature (up to -4.75D) = steepening of K’s up to 3.9D
Mean change in VA of 2 snellen lines
Peripheral MECs = hyperopic shifts
Paracentral/ central MECs= myopic shifts
Patient education
Consider educating the patient on the following:
ADCs affect the cornea and may cause blurred vision or dry eye
Your need for glasses may change, often week to week
The use of ADCs may affect your ability to read fine print or drive
Once treatment is complete, paused, or with dose reduction: changes are reversible
Treatment
Keratopathy
Preservative free artificial tears
Restates / xiidra to treat concomitant dry eye disease
Treat concomitant blepharitis
Pred Forte use is debated
Refractive error
At home trial lenses
OTC readers
Contact lenses should be avoided
Monitoring
Eye care practitioners should grade events such as keratitis on a scale from 1-4.
Findings should be reported to oncologist, especially for black box warnings
Some drugs like ELAHERE require an ocular assessment form to be filled out on the following occasions: baseline exam, every other cycle for first 8 cycles, and as clinically indicated
Immunotherapy Checkpoint Inhibitors
Immunotherapy checkpoint inhibitors are a class of drugs designed to enhance the body's immune system to fight cancer. While they have shown remarkable success in treating various malignancies, some individuals may experience ocular side effects as a result of immune system activation. These side effects can include inflammation of the eyes, dry eyes, and, in rare cases, more severe conditions such as uveitis or immune-related adverse events affecting the optic nerve, underscoring the importance of close monitoring and early intervention in patients undergoing checkpoint inhibitor therapy.
Ocular Side Effects
Inflammation of the eye
Rare, only in ~1% of patients
Can occur in all layers of the eye
Ex: eyelid inflammation, EOMs, ocular surface, uveal tract, retinitis, CME, retrobulbar, etc
Patient Education
Patients should be encouraged to return to office for evaluation if any of the following symptoms occur:
Blurred vision
Redness
Photosensitivity
Once treatment is complete, paused, or with dose reduction: changes can be reversible depending on part of eye involved.
Treatment
Oral or topical steroids depending on location of inflammation
MAP K Inhibitors
MAP kinase (MAPK) inhibitors are medications that target the MAP kinase pathway, commonly used in cancer treatment. When used systemically, they may have ocular side effects, including dry eyes, blurry vision, and, in some cases, more severe complications like retinopathy or uveitis. Monitoring and addressing these ocular side effects are essential aspects of managing patients undergoing MAP kinase inhibitor therapy.
Ocular Side Effects
MEKi
15% of patients can get fluid behind the retina → blurred vision
Fluid revolves on its own but sometimes dose-holds are required
<0.3% of patients may develop bleeding behind the eye which can cause more drastic changes to vision
BRAFi
5% of patients may develop inflammation of the eye, which can be treated with a steroid drop
May develop squamoproliferative eyelid lesions
Treatment
MEKAR
Observation / dose hold as deemed by drug company
Retinal vein occlusion
Antivegf intravitreal injection
Topical drops to control IOP
Uveitis
Steroid drops
Squamoproliferative lesions
Surgical excision
For further insights into this subject, click on this link to access Dr. Julia Canestraro, O.D.'s course titled "New Cancer Drugs and Why Optometrists Should Pay Attention." By participating, you can also earn one hour of free continuing education (CE).
