At A Glance
- The most common ocular side effects of anticancer medications are related to dry eye and conjunctivitis.
- Cessation of treatment often leads to resolution of side effects, but any decision of this nature must be discussed with the patient’s oncologist.
- Being aware of the ocular side effects of anticancer treatments is an important part of the optometrist’s role in comanaging patients with cancer.
Many of us have patients who are being treated for cancer and may be experiencing or at risk for ocular side effects of their treatment. It is important for optometrists to be aware of the risk of side effects related to cancer treatment so that we can monitor, help manage, and provide comfort to patients in a difficult time.
This article reviews the ocular side effects of treatments commonly used for patients with cancer. Understanding these effects can help us to better anticipate what our patients may experience and how best to handle these complications.
RADIATION AND INTERFERON
Radiation is an area-targeted treatment, so, unless the area treated is near the eye, it is unlikely there will be ocular effects. Patients who are treated with radiation in or near the eye may experience pigmentation changes, peeling of the skin, blisters, and skin photosensitivity, among other things. Those who are being treated with both chemotherapy and radiation at the same time may note an increase in severity of the side effects associated with a particular chemotherapy drug.
Interferon is a natural substance made by our white blood cells that helps our body’s immune system fight infection and disease. Interferon can also be made in a laboratory, and can be used to help control the growth of cancer or to kill cancer cells. Because interferons are cytokines, they are considered a type of immunomodulatory agent. These medications can be delivered intravenously, intramuscularly, or via the urethra.
CHEMOTHERAPY AND BIOLOGICS
Chemotherapy agents are delivered either intravenously or orally in pill form, and they may or may not be used in conjunction with radiation. Which drug, how often, and how many treatments are required depends on the type and location of the cancer and its staging (Table 1). Many times chemotherapy drugs (Table 2) are not used alone, but rather multiple drugs are used at the same time and are coupled with steroids.
Biologic drugs, or biologics, are compounds produced from living organisms or containing components of living organisms. There are many biologic drugs currently in use by oncologists to disrupt the growth and survival of cancer cells.1 In theory, biologic therapies have fewer side effects (Table 3) than cytotoxic drugs, which are less specific in the cells that they target.
Any of these medications can have side effects, including ocular side effects, as outlined in the sections below. When these occur, cessation of treatment may be an option to relieve the unwanted effects, but the risks and benefits of this decision must be weighed and discussed with the patient’s oncologist.
ANTERIOR SEGMENT AND ADNEXAL SIDE EFFECTS
The most common ocular side effects of anticancer medications are related to dry eye and conjunctivitis. Patients frequently report symptoms including epiphora, blurred vision, foreign body sensation, blepharitis, eye pain, photophobia, and redness.
Treating these patients is the same as treating any other patient with dry eye disease or blepharitis. While examining the patient, determine the underlying cause (eg, meibomian gland dysfunction related to evaporative dry eye or poor tear production). Based on this, choose appropriate care, including topical lubricants, lid hygiene, warm compresses, nutraceuticals, in-office lid treatments, and topical medications such as ocular steroids, cyclosporine, or lifitegrast ophthalmic solution 5% (Xiidra, Novartis).
Epiphora, in a few cases, has been shown to be caused by permanent lacrimal gland stenosis in patients receiving a chemotherapy regimen of cyclophosphamide, methrotrexate, and 5-fluorouracil.2,3 These patients may require corrective surgery after treatment.
Periorbital cutaneous changes such as hyperpigmentation can occur with chemotherapy, and the likelihood of this increases with higher dosages. There is nothing available to treat these changes, but they sometimes resolve after cessation of treatment. Periorbital edema can also occur with chemotherapy and with use of biologics such as methotrexate, 5-fluorouracil, erlotinib, pazopanib, and imatinib.2 Patients may respond well to cold compresses and in some cases topical or oral steroids.
Trichiasis and ectropion, which can lead to corneal irritation and in worst cases cornea ulcers, have been noted as side effects of 5-fluorouracil, gefitinib, erlotinib, cetuximab, and panitumumab. Heavy lubrication, along with lash epilation, will help to control the corneal irritation. In some cases, oculoplastic surgery may be needed to reverse long-term ectropion. If a patient develops an ulcer or abrasion from these sequelae, treat appropriately and address the underlying problem to avoid recurrence.
Posterior subcapsular cataracts have been known to form with the use of large doses of busulfan.2,4 Depending on the level of the visual effect, these patients may need cataract surgery.
Patients who have had a full or partial corneal transplant should be monitored closely when undergoing interferon treatment. Acute rejection has been reported with the use of alpha-2 interferon.3
POSTERIOR SEGMENT SIDE EFFECTS
Posterior segment side effects of anticancer medications can cause decreased vision. Some changes can be permanent and others temporary. Cisplatin and topoisomerase inhibitor type II have been found to cause central retinal artery occlusions, and retinal vein occlusions have been seen with vandetanib (Caprelsa, Genzyme).2,3,5-7 These changes should be comanaged with a retina specialist.
Visual field defects can vary depending on the medication. The chemotherapy drug cisplatin can cause central scotoma or homonymous hemianopsia.2 General visual field defects have been seen with use of paclitaxel (Abraxane, Celgene) and oxaliplatin (Eloxatin, Sanofi-Aventis). The effects of oxaliplatin were found to be temporary in most cases and resolved within 3 weeks of medication cessation.8 In more extreme cases, transient cortical blindness has been reported in relation to the use of some chemotherapy drugs and biologic agents.2,3,9 Discussion with patients regarding adaptation to visual changes and prognosis for improvement is important. Temporary prisms and other low vision devices may be helpful in improving these patients’ quality of life.
Retinopathy can occur with mitotane (Lysodren, HRA Pharma), tamoxifen (Soltamox, Fortovia Therapeutics), and interferon treatment.1 Patients are typically treated with tamoxifen for 5 years and should be seen annually for appropriate testing and dilation to monitor for toxicity. Approximately 3% of patients on tamoxifen treatment may develop macular crystals or drusen, along with pigmentary changes.3 Tamoxifen is an estrogen receptor modulator, and it has been reported to cause bilateral optic neuritis leading to optic atrophy and vision loss in high doses.3 All of these findings will typically resolve with cessation of medication, but it is important to monitor patients closely to identify any toxicity as early as possible.
NEURO-OPHTHALMIC SIDE EFFECTS
Neurotoxic side effects of chemotherapy such as optic neuropathies are well documented. These can manifest as papilledema, retinal edema, and optic neuritis. There have been cases of unilateral and bilateral retrobulbar neuritis, linked often to patients receiving high doses or high cumulative doses of chemotherapy.2,5-7 Patients receiving chemotherapy via intracarotid injection have presented with more severe ocular and orbital toxicity including ipsilateral retrobulbar neuritis.3
Administration of carboplatin via sub-Tenon injection has been associated with ocular motility restriction, resulting in diplopia.2 This should resolve over time with no lasting effects.
Neurotoxic side effects can also be associated with the use of interferon treatment. Unilateral and bilateral anterior ischemic optic neuropathy has been shown to occur with use of interferons.1 In the long term, this can lead to optic nerve atrophy and permanent vision loss.
KNOWLEDGE AND COMPASSION: A WINNING COMBINATION
Even in the era of COVID-19 when we may not be able to physically hold our patients’ hands, it is important for us to reach out and show compassion and help as much we can. Being aware of the ocular side effects of anticancer treatments and alleviating patients’ discomfort when possible are important parts of our role in comanaging patients with cancer.
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- 2. Singh P, Singh A. Ocular adverse effects of anti-cancer chemotherapy. Journal of Cancer Therapeutics and Research. 2012;1:5.
- 3. Omoti AE, Omoti CE. Ocular toxicity of systemic anticancer chemotherapy. Pharm Pract (Granada). 2006;4(2):55-59.
- 4. Mendez CAM, Aronow ME, Amescua G, Singh AD. Tumor-associated cataract. In: Singh AD, Damato BE, eds. Clinical Ophthalmic Oncology. 3rd ed. Cham, Switzerland; Springer; 2019:173-183.
- 5. Ostrow S, Hahn D, Wiernik PH, Richards RD. Ophthalmologic toxicity after cis-dichlorodiammineplatinum (II) therapy. Cancer Treat Rep. 1978;62:1591-1594.
- 6. Caraceni A, Martini C, Spatti G, Thomas A, Onofrj M. Recovering optic neuritis during systemic cisplatin and carboplatin chemotherapy. Acta Neurol Scand. 1997;96(4):260-261.
- 7. Cohen RJ, Cuneo RA, Cruciger MP, Jackman AE. Transient left homonymous hemianopsia and encephalopathy following treatment of testicular carcinoma with cisplatinum, vinblastine, and bleomycin. J Clin Oncol. 1983;1(6):392-393.
- 8. Noor A, Desai A, Singh M. Reversible ocular toxicity of oxaliplatin: a case report. Cureus. 2019;11(5):e4582.
- 9. Byrd RL, Rohrbaugh TM, Raney RB, Norris DG. Transient cortical blindness secondary to vincristine therapy in childhood malignancies. Cancer. 1981;47:37-40.