Ocular (Eye) Adverse Effects of Cancer Treatments: Important Information and Recommendations

The range of cancer treatments continues to expand. Where surgery, radiotherapy and chemotherapy were once the main approaches, today's options include targeted drugs, immunotherapies, hormonal treatments, interventional oncology techniques such as freezing and thermal ablation, gene therapy and dual-action drugs . Although newer treatments aim to target cancer cells without harming healthy cells, adverse effects can occur, including ocular, or eye-related, problems.

Eye-Related Adverse Effects of Cancer Treatment

Chemotherapy and Conventional Cancer Drugs:

• Bortezomib: Meibomian Gland Dysfunction: Bortezomib can cause meibomian gland dysfunction. These oil glands in the eyelids provide an oily layer over the tear film, preventing evaporation. When they do not function properly, dry eyes and discomfort can result.
• Taxanes and Fluoropyrimidines: Excessive Tearing: These anticancer drug groups can cause excessive tearing due to increased tear production or impaired drainage.
• Methotrexate and Anthracyclines: Dry Eye and Conjunctivitis: These medicines can cause dry eye and conjunctivitis. Dry eye results from insufficient tears or poor tear quality, while conjunctivitis is inflammation of the membrane covering the white of the eye and the inner eyelid.
• Cytarabine: Visual Impairment of up to 85%: Cytarabine can cause visual impairment of up to 85%, arising from its effects on the nervous system.
• Interferon-Alfa 2b: Uveitis and Retinal Capillary Occlusion: Interferon-alfa 2b can cause uveitis and retinal capillary occlusion. Uveitis is inflammation inside the eye, while retinal capillary occlusion blocks the small vessels supplying the retina. Patients receiving interferon-alfa 2b should be informed, and ocular symptoms should be monitored closely.
• Cisplatin: Ischemic Retinopathy: Cisplatin can cause ischemic retinopathy, which develops when the retina receives insufficient blood flow.

Immune Checkpoint Inhibitors:

The newest and most widely used class of immunotherapies, immune checkpoint inhibitors, activates the immune system against tumors. However, these agents may cause uveitis and white dot syndrome. They include PD-1 (programmed cell death protein 1) inhibitors, PD-L1 (programmed death ligand 1) inhibitors and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) inhibitors.

Despite their anticancer effectiveness, checkpoint inhibitors can cause ocular adverse effects. Two important examples are:

1. Uveitis: Checkpoint inhibitors may cause inflammation of the uvea, the middle layer of the eye, potentially leading to severe vision loss. Immune activation can trigger inflammation and damage inside the eye. Symptoms include eye pain, redness, light sensitivity and blurred vision.
2. White Dot Syndrome: Checkpoint inhibitors may damage retinal photoreceptors, the cells sensing light, and cause white dot syndrome. White lesions in the retina can reduce visual acuity. This is generally a less common ocular adverse effect and may improve after the drug is stopped.

Management depends on symptom severity and the type of ocular adverse effect. The general aim is to relieve inflammation and symptoms. Options may include:

• Topical Steroids: Mild-to-moderate uveitis may be treated with steroid eye drops such as prednisolone acetate to reduce inflammation and discomfort. Dose and frequency depend on the patient's condition and medical advice.
• Oral and IV Steroids: Severe uveitis or other ocular inflammation may require oral steroids such as prednisone. Dose depends on weight and severity and is generally tapered as prescribed. A typical starting oral prednisone dose may be 40-60 mg/day, followed by a gradual reduction under medical guidance. Intravenous corticosteroids such as IV methylprednisolone may be given at 250 mg to 1000 mg daily. Doses can be adjusted to response, and treatment is usually short-term.
• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): In some cases, topical or oral NSAIDs such as ibuprofen may effectively reduce inflammation.
• Immunosuppressive Drugs: Severe uveitis that does not respond to steroids may require methotrexate, azathioprine or cyclosporine. These medicines suppress immunity to reduce inflammation and improve eye health.
• Biological Agents: Severe uveitis unresponsive to steroids and immunosuppressants may be treated with biological agents such as infliximab or adalimumab. They reduce inflammation by targeting immune cells or inflammation-triggering molecules.
• Stopping Immune Checkpoint Inhibitors: Your oncologist may stop immunotherapy if ocular adverse effects are severe or unresponsive to treatment.

MEK Inhibitors:

MEK inhibitors target proteins to stop cancer cell growth and proliferation. These proteins are important in cancers such as melanoma and some lung cancers. Examples include trametinib, cobimetinib and binimetinib. These drugs may cause serous retinal detachment during the first weeks of treatment, with fluid accumulating in the eyes. This is generally mild and temporary.

Radiotherapy:

Radiotherapy for tumors in or around the eye can damage different ocular structures. It often causes dry eye and, with prolonged treatment, may cause radiation retinopathy involving inflammation, bleeding and edema.

Tyrosine Kinase Inhibitors:

These drugs inhibit cancer cell growth and proliferation by targeting the enzyme tyrosine kinase. Examples include imatinib, sunitinib and dasatinib. They may cause periorbital swelling and edema. Anti-EGFR agents used in some lung and colorectal cancers can also cause ocular adverse effects. Erlotinib and gefitinib are common examples. These effects are thought to occur because EGFR is also present in eye tissues and important for normal function. They may include dry eye, conjunctivitis, eyelash abnormalities, corneal thinning, erosion and, rarely, perforation, potentially causing pain, light sensitivity and vision loss.

BRAF Inhibitors:

BRAF inhibitors target the growth-promoting BRAF gene found in cancers such as melanoma and some lung cancers. Examples include vemurafenib and dabrafenib. Often used when other options have failed, they may cause ocular inflammation, dry eye and other adverse effects.

CDK4/6 Inhibitors:

CDK4/6 inhibitors suppress cancer cell growth and proliferation by targeting cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). They are used particularly for hormone receptor-positive, HER2-negative breast cancer. Ocular adverse effects of CDK4/6 inhibitors are not fully understood, but by affecting normal cellular CDK4 and CDK6 function, they may cause dry eye and other ocular problems that are generally mild and temporary.

These adverse effects result from cancer drugs or treatment methods harming healthy cells. Physicians should therefore monitor eye health closely and take appropriate precautions. Patients should report any ocular problems during treatment so that suitable management can be provided.

A Review of Cancer Treatments' Ocular Adverse Effects

A study published in Scientific Reports on January 12, 2021 examined ocular changes and adverse effects in people receiving certain biological cancer treatments. It reviewed 22 patients referred to ocular oncology for eye complaints between 2012 and 2017. They had various cancers and treatments and were divided into four groups by drug class:

1. Group: Molecularly targeted therapies: BRAF inhibitors (vemurafenib) + MEK inhibitors (trametinib, pimasertib)
2. Group: Immune checkpoint inhibitors: cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab) and programmed death ligand-1 (PD-L1, durvalumab)
3. Group: Therapeutic antibodies/immune system molecule: anti-epidermal growth factor receptor (EGFR inhibitor) + anaplastic lymphoma kinase (ALK, alectinib)
4. Group: Other: Bacillus Calmette-Guerin, ibrutinib, ixazomib, pemetrexed

The study offers a comparative analysis of ocular adverse effects associated with immunotherapy, particularly biological treatments.

Ocular adverse effects occurred in 18 of 22 patients (81.8%), including uveitis, dry eye and central serous retinopathy. One patient developed central retinal artery occlusion (CRAO), and another developed branch retinal vein occlusion (BRVO).

Treatments used for the different drugs and ocular adverse effects in this study included:

• Inflammatory Uveitis: This was the most common adverse effect (40.9%). Topical or systemic corticosteroids were given to 13 patients without stopping biological treatment. All showed improvement in inflammation, symptoms and vision.
• Dry Eye Syndrome: Patients with dry eye received preservative-free artificial tears and topical cyclosporine (1%), with improvement in symptoms.
• Central Serous Retinopathy (CSR)-Like Reaction: No patients required treatment for CSR-like reactions. Subretinal fluid was absorbed in all cases, and the condition resolved without intervention.
• Retinal Artery Occlusion (CRAO) and Retinal Vein Occlusion (BRVO): Both patients developed serious ocular adverse effects after biological therapy. Although CRAO and BRVO are rare, their severe visual consequences require increased awareness and urgent assessment when ocular symptoms arise during or after biological treatment.

Overall, 81.8% of patients had ocular adverse effects, including uveitis, dry eye syndrome, central serous retinopathy and retinal artery or vein occlusion. The study shows that biological treatments can cause ocular problems, including serious pathology. Regular ophthalmological assessment before, during and after therapy is therefore important, with urgent referral for patients reporting eye complaints. This approach may improve early detection and eye health. Collaboration between ophthalmologists and oncologists can play a vital role in cancer care.