27.2Orbital, Periorbital, and Orbital Teratogenic Side Effects by Individual Drug

IC, intracarotid

aDrugs are known to cause the indicated side effect unless “(maybe)” appears after the drug name, in which case the drug is considered a possible cause of the side effect

in Tables 27.1 and 27.2. Much of the information on chemotherapy-related side effects was gleaned from the Web site of the National Registry of Drug-Induced Ocular Side Effects [1].

27.2.1 Busulfan

Busulfan (Busulfex, Myleran) is an alkylating agent most often used for treatment of granulocytic leukemia and other blood dyscrasias. Its use has been associated with keratitis sicca, eyelid hyperpigmentation, angioneurotic edema, and loss of eyelashes and eyebrows. Other possible side effects include myasthenia-like paresis of extraocular muscles causing diplopia and ptosis; exfoliative dermatitis; and erythema multiforme [2]. Possible teratogenic effects include microphthalmia [3, 4].

27.2.2 Capecitabine

Capecitabine (Xeloda) is a fluoropyrimidine antimetabolite most often used for treatment of metastatic breast cancer and colorectal cancer. Its use has been associated with chemosis, conjunctival erythema, and nonspecific conjunctivitis [2]. While epiphora can be seen in association with capecitabine, the experience at

The University of Texas M.D. Anderson Cancer Center suggests that there is no anatomic correlate of canalicular or nasolacrimal duct blockage with this symptom (B. Esmaeli, personal communication).

27.2.3 Carmustine

Carmustine (BiCNU, Gliadel) is a nitrosourea most often used to treat central nervous system tumors. Its use has been associated with blepharoconjunctivitis, chemosis, conjunctival hyperemia, and conjunctival hemorrhage. Allergic reactions and skin hyperpigmentation have also been noted [2].

Intracarotid injections of carmustine have been associated with vasodilation, proptosis, pain, and edema of the orbit. Additionally, rectus muscle fibrosis and internal ophthalmoplegia have occurred [2, 5–7].

27.2.4 Cetuximab

Cetuximab (Erbitux) is a monoclonal antibody that binds to epidermal growth factor receptors and has been used to treat metastatic colorectal cancers and cancers of the head and neck. Its use has been associated with squamous blepharitis and conjunctival hyperemia and conjunctivitis [7]. There is also a possible association between cetuximab and exfoliative dermatitis and eyelash trichomegaly. Trichomegaly has been reported to develop after 10 weeks of treatment. It is speculated that trichomegaly is a result of epidermal growth factor receptor inhibition causing increased terminal differentiation of eyelash follicles [8–10]. Eyelashes return to normal 1 month after cessation of cetuximab therapy [10].

27.2.5 Cisplatin

Cisplatin (Platinol, Platinol-AQ) is most commonly used to treat metastatic testicular, ovarian, and bladder carcinomas. Its use has been associated with conjunctivitis, eyelid and conjunctival erythema and edema, urticaria, and loss of eyelashes and eyebrows. Orbital pain has also been reported. There is possible myasthenia-like neuromuscular blockade causing diplopia and ptosis from paresis of extraocular muscles [2].

Intracarotid injections of cisplatin have been associated with ipsilateral orbital pain, periorbital erythema and edema, and cavernous sinus syndrome. Injection into the distal ophthalmic artery was reported to cause massive orbital edema within days of administration. There was accompanying uveal effusion, retinal detachment, ophthalmoplegia, and blindness [11]. Another report described extreme facial/periorbital edema, proptosis, and chemosis, also followed by irreversible