The Evaluation of Ocular Toxicity of Chemotherapy
The Evaluation of Ocular Toxicity of Chemotherapy
The Evaluation of Ocular Toxicity of Chemotherapy
Seyed Mojtaba Sohrevardi PhD1, Morteza Zangeneh Soroush PhD2, Hamid Owliaey MD*3,
Elnaz Sheikhpour PhD4
1. Department of Pharmacotherapy, Facullty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2. Department of Biomedical Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran
3. Department of Forensic Medicine & Clinical Toxicology, Yazd Branch, Islamic Azad University, Yazd, Iran
4. Hematology and Oncology Research center, Shahid Sadoughi hospital, Shahid Sadoughi University of Medical Sciences,
Yazd, Iran
*Corresponding author: Dr. Hamid Owliaey, Department of Forensic Medicine & Clinical Toxicology, Yazd Branch,
Islamic Azad University, Yazd, Iran. Email: [email protected], ORCID ID: 0000-0001-5642-9584
Abstract
Cancer continues to pose a substantial global health burden and remains one of the leading causes of mortality
worldwide. Encouragingly, survival rates have consistently improved, largely due to advancements in diagnosis
and treatment. The development of anticancer drugs, including cytotoxic chemotherapy, hormonal agents, and
targeted therapies, has significantly enhanced the efficacy of cancer treatments.
Chemotherapy-induced ocular toxicity encompasses a wide range of disorders, influenced by the eye's unique
anatomical and physiological characteristics. The mechanisms of these drugs can lead to systemic and ocular
side effects, including cytotoxicity, inflammation, and neurotoxicity. While ocular side effects from targeted
therapies are less common, they can be severe, disabling, and potentially irreversible. In some cases, immediate
discontinuation of the drug may be necessary to prevent vision-threatening complications.
Understanding these ocular side effects is crucial for early recognition and intervention by ophthalmologists and
oncologists to prevent blindness. Additionally, anticipating treatment-related toxicities enables pharmacists to
develop strategies that minimize or mitigate these side effects.
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This review focuses on the ocular toxicity associated with the most significant anticancer chemotherapeutic
agents.
Keywords: Chemotherapy, Cyclophosphamide, Ocular, Tamoxifen, Toxicity
Introduction
Cancer is a class of disorders defined by Tumors can be removed surgically,
the body's aberrant and uncontrollably whereas radiotherapy uses ionizing
dividing cells. These cancerous cells have radiation to shrink tumors and kill cancer
the capacity to spread to different tissues cells. Anticancer medications either
or organs from their original location (1- increase the cytotoxicity of cancer cells or
4). An estimated 38.4% of people are block specific pathways necessary for
expected to receive a cancer diagnosis at cancer progression. These medications are
some point in their lives, according to the integral to cancer therapy, either as
US National Cancer Institute (5). Patients standalone treatments or in combination.
and their families bear severe financial and However, cytotoxic anticancer drugs target
psychological costs as a result (6). Despite rapidly dividing cancer cells, and they can
these obstacles, improvements in diagnosis also damage healthy cells, particularly in
[ DOI: 10.18502/ijpho.v14i4.16603 ]
and treatment have led to a noteworthy the vascular, neurological, immune, and
20% increase in survival rates over the muscular systems. Additionally, the
past three decades (5- 7). Cancer treatment delicate balance of the ocular surface is
commonly involves a combination of vulnerable to chemotoxicity, leading to
approaches, including tumor-removal inflammatory, neurological, and cytotoxic
surgery, hormonal agents, anticancer effects (7).
medications, and radiation therapy.
Sohrevardi et al
Although some studies have reviewed the patients have noted occurrences of visual
ocular surface side effects, understanding disturbances and conjunctivitis as side
the underlying mechanisms remains effects (8).
limited. In addition, due to high prevalence Busulfan
of cancer in our country (3), it is Busulfan, an alkylating agent with
necessary to review such a study, myeloablative properties, inhibits DNA
therefore, this study aims to investigate replication by inducing DNA crosslinking,
ocular toxicity of chemotherapy drugs. leading to cell apoptosis. It is employed as
Anticancer drug a preparative regimen before
Cancer therapies can be broadly divided hematopoietic stem cell transplantation
into three categories: (1) hormonal agents; due to its cytotoxic effects on host
(2) conventional cytotoxic chemotherapy, hematopoietic stem and progenitor cells.
which causes cell death and reduces tumor Busulfan infusion has been linked to dry
burden by interfering with DNA synthesis eyes (keratoconjunctivitis sicca) in patients
and cellular division; and (3) the more undergoing treatment for chronic myeloid
recent molecularly targeted therapies, leukemia and other myeloproliferative
which are more precisely designed to disorders (9, 10).
target specific cellular functions in cancer 5-Fluorouracil (5-FU)
cells rather than normal cells. Molecularly 5-Fluorouracil, also known as 5-FU, is a
targeted therapies have become integral in chemotherapy drug used to treat various
systemic treatments across various cancer cancers. It is FDA-approved for gastric
types, operating through mechanisms adenocarcinoma, pancreatic
distinct from traditional cytotoxic adenocarcinoma, breast adenocarcinoma,
chemotherapy by targeting cellular and colorectal adenocarcinoma. 5-FU
signaling and angiogenesis pathways functions by inflicting damage to DNA,
crucial for tumor growth (7). In this article, especially the p53 gene, which is essential
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we aim to explain the ocular side effects of for controlling the course of the cell cycle
the most important chemotherapy drugs. and the response to DNA damage. More
Cyclophosphamide than 50% of colorectal cancers, the p53
Cyclophosphamide is used alone or in gene is overexpressed. Ocular side effects
combination with other anticancer drugs to associated with 5-FU include blurred
treat leukemias, malignant lymphomas, vision, swelling around the eyes, eye pain,
and various solid tumors, including breast sensitivity to light, excessive tearing,
cancer, testicular cancer, small cell lung conjunctivitis, eyelid inflammation,
carcinoma, neuroblastoma, and Ewing's corneal inflammation, scar formation on
sarcoma. Patients receiving the eyelid, eyelid adhesion, and rarely
cyclophosphamide, particularly those with narrowing of the tear ducts. A study
breast cancer, may experience ocular reported that half of the patients using 5-
symptoms such as dry eyes FU developed defects in the outer layer of
(keratoconjunctivitis sicca), inflammation the cornea, which resolved after several
of the eyelids and conjunctiva weeks (8, 10). In a separate study, the
(blepharoconjunctivitis), and reversible estimated prevalence rates of ocular
excessive tearing (8, 9). surface lesions associated with systemic 5-
[ DOI: 10.18502/ijpho.v14i4.16603 ]
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provided that the original author and source are credited.
The Evaluation of Ocular Toxicity of Chemotherapy Drugs
findings typically resolve gradually with have reported painful keratitis with fine
treatment cessation. Additionally, one case opacities in the corneal epithelium shortly
study documented the development of after starting treatment, which typically
vitiligo in a patient during the eighth week resolves within a week after stopping the
of interferon alpha-2a therapy for active medication. Moreover, two leukemia
chronic hepatitis C (13). Interferon is patients in remission experienced
known to cause retinopathy. This significant bilateral vision loss following
condition typically presents with retinal combined chemotherapy, CNS irradiation
hemorrhages and cotton wool spots in the prophylaxis, and intrathecal cytarabine
posterior fundus, although it generally administration (14).
preserves visual function. However, there Methotrexate
is a risk of macular edema, which can lead Methotrexate (MTX) is an anticancer
to decreased visual acuity in some cases. medication used to treat various malignant
Patients with cancer who are diseases. It functions as a therapeutic
asymptomatic may also develop ischemic agent for treating both cancers and
retinopathy produced by interferon. Many autoimmune conditions, acting through
times, these alterations in the retina are chemotherapy and immunosuppression
[ DOI: 10.18502/ijpho.v14i4.16603 ]
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution
provided that the original author and source are credited.
Sohrevardi et al
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution
provided that the original author and source are credited.
The Evaluation of Ocular Toxicity of Chemotherapy Drugs
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution
provided that the original author and source are credited.
Sohrevardi et al
related to intravenous doxorubicin are anomalies were observed three weeks after
infrequent, with only a small percentage of the start of therapy and went away entirely
patients experiencing symptoms like when the tamoxifen (8) was stopped.
increased tearing and conjunctivitis (8). Furthermore, there are notable adverse
Mitotane effects of tamoxifen on the optic nerve,
Mitotane is the sole approved medication retina (retinopathy), and lens (cataracts)
for managing advanced adrenocortical (9).
carcinoma and for postoperative adjuvant Plant alkaloids
therapy. Its primary action involves Vinca alkaloids, such as vincristine,
destroying the adrenal cortex, which vinblastine, vindesine, and vinorelbine are
disrupts steroid hormone production, widely used in oncology as antineoplastic
although the precise molecular mechanism drugs, either alone or in combination with
remains uncertain. Nonetheless, certain polychemotherapy. These agents exert
confounding factors in in vitro their cell cycle-dependent action by
experiments might diminish the inhibiting tubulin polymerization into
applicability of specific studies (45). microtubules. Ocular toxicity associated
Ocular adverse effects are rare but can with these plant alkaloids includes cranial
include impaired vision, diplopia, lens nerve palsies, optic neuropathy and
opacities, toxic retinopathy with atrophy, cortical blindness, and night
papilledema, and retinal hemorrhage. blindness. A recent study demonstrated
Systemic side effects are common in optic neuropathy in three patients after a
patients receiving mitotane (14). cumulative 48 mg dose of vincristine,
Tamoxifen presenting with poor visual acuity and
For the majority of instances of metastatic optic disc pallor. One case of bilateral
breast cancer, tamoxifen, an estrogen optic atrophy resulted in blindness.
antagonist, is seen to be the best course of Additionally, night blindness was observed
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This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution
provided that the original author and source are credited.
The Evaluation of Ocular Toxicity of Chemotherapy Drugs
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution
provided that the original author and source are credited.
Sohrevardi et al
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution
provided that the original author and source are credited.
The Evaluation of Ocular Toxicity of Chemotherapy Drugs
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This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution
provided that the original author and source are credited.
Sohrevardi et al
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution
provided that the original author and source are credited.