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27 Orbital and Periorbital Side Effects of Chemotherapy

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Fig. 27.1 Periorbital erythematous rash on lower eyelid skin and cheek in a patient with breast cancer treated with docetaxel. Photo courtesy of Dr. Bita Esmaeli

Fig. 27.2 Trichomegaly associated with erlotinib in a patient with glioblastoma multiforme. The eyelashes had to be trimmed every

3 months to keep the patient comfortable and prevent visual obstruction. Photo courtesy of Dr. Bita Esmaeli

been associated with epiphora and trichomegaly of the eyelashes and eyebrows with coarse, brittle, irregular eyelash growth (Fig. 27.2). Secondary corneal ulcerations due to eyelash–corneal contact have also been reported [13, 14].

27.2.11 Etoposide

Etoposide (Vepesid) is used to treat multiple systemic malignancies and also irreversibly inhibits Cytomegalovirus replication. Its intracarotid administration has caused orbital inflammation and proptosis [2, 15].

334

J.D. Ng

27.2.12 Fluorouracil

Fluorouracil (Carac, Efudex, Fluoroplex) is a fluorinated pyrimidine used for treatment of colon, rectal, breast, stomach, and pancreatic cancer. It is also used topically for treatment of actinic keratoses and for glaucoma surgery. Its systemic use has been associated with cicatricial ectropion, blepharoconjunctivitis, conjunctival erythema and edema, ankyloblepharon, dermatitis, keratinized eyelid margins, and loss of eyelashes and eyebrows. It may also induce blepharospasm [24, 16].

Subconjunctival injection of fluorouracil has caused periorbital edema. Local injection into the eyelid also causes cicatricial ectropion and may cause loss of eyelashes [2, 5, 17].

27.2.13 Imatinib Mesylate

Imatinib mesylate (Gleevec) selectively inhibits bcr-abl and platelet-derived growth factor receptor tyrosine kinase and is used as targeted therapy for myelogenous leukemia and gastrointestinal stromal tumors [2]. Its use has been associated with edema of the orbit, eyelids, and conjunctiva. Periorbital edema associated with imatinib rarely requires surgical intervention [18]. Most cases can be managed conservatively with occasional judicious use of diuretics. Imatinib may also cause chemosis, eyelid hypopigmentation, blepharoconjunctivitis, Stevens–Johnson syndrome, and toxic epidermal necrolysis [2, 1821]. Epiphora has also been reported in association with imatinib, but with no associated anatomic narrowing of the canaliculi or nasolacrimal ducts [22, 23].

27.2.14 Interferons

Interferons (Actimmune, Alferon N, Avonex, Betaseron, Infergen, Intron A, PEGASYS, PEG-Intron, Rebif, Roferon-A) are used to treat chronic viral infections, chronic blood dyscrasias, and multiple sclerosis. Their use has been associated with orbital pain, subconjunctival hemorrhage, trichomegaly [24], and possibly Graves ophthalmopathy [25]. Ocular myasthenia-like findings have also been mentioned in a patient treated with 12 weeks of low-dose interferon alpha 2b therapy. There was no resolution of the myasthenia years after cessation of treatment [2, 26].

27.2.15 Interleukin-2, Interleukin-3, and Interleukin-6

Interleukin-2 (Proleukin), interleukin-3, and interleukin-6 are used for treatment of metastatic renal cell carcinoma and melanoma. Administration of these interleukins has been associated with eyelid pruritus, macular erythema, desquamative rash, angioneurotic edema, urticaria, and transient subcutaneous lymphoma [2, 27].

27 Orbital and Periorbital Side Effects of Chemotherapy

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27.2.16 6-Mercaptopurine

6-Mercaptopurine (Purinethol) is a purine analog used to treat acute and chronic leukemia. Its use has been associated with eyelid hyperpigmentation and icterus. It may also be associated with microphthalmia as a teratogenic effect [2, 28].

27.2.17 Methotrexate

Methotrexate is a folic acid antagonist used in treating neoplasms, rheumatoid arthritis, psoriasis, and uveitis. Its use has been associated with eyelid erythema, blepharoconjunctivitis, seborrheic blepharitis depigmentation of the eyelids, eyelid hyperpigmentation, urticaria, and loss of eyelashes and eyebrows [2, 5]. Orbital edema has also been reported. Periorbital edema, blepharitis, and conjunctival hyperemia occur in up to 25% of patients receiving methotrexate [1, 2]. Findings may be related to change in metabolism of the meibomian glands [25, 23].

27.2.18 Mitomycin C

Mitomycin C (Mutamycin, Mitozytrex) is mostly used topically for treatment of conjunctival intraepithelial neoplasia or primary acquired melanosis with atypia. It can cause allergic reactions and blepharitis. Symblepharon formation is also a common finding with prolonged use [2]. Punctal and canalicular stenosis have also been reported in association with topical mitomycin C [2].

27.2.19 Mitoxantrone Dihydrochloride

Mitoxantrone (Novantrone) is used to treat acute leukemias and breast and ovarian cancer. Its use has been associated with eyelid edema, conjunctivitis, and, interestingly, blue-green pigmentation of the eyelid [2, 29, 30].

27.2.20 Plicamycin

Plicamycin (Mithracin) is used to treat testicular cancer. Its use may be associated with periorbital pallor [2, 4, 5].

27.2.21 Thiotepa

Thiotepa is used to treat breast and ovarian carcinomas, lymphomas, Hodgkin disease, and some sarcomas. Topical use of thiotepa has been associated with