Orbit
Chemotherapy related Orbital injury:
This section gives a more detailed outline of the effects of chemotherapy on the orbit.
- Cyclophosphamide, ifosfamide and methotrexate alter the normal tear film physiology by:
- Causing inflammation of the lacrimal glands
- Being excreted directly into tears
- This can lead to dry eye symptoms and inflammation around the eyelids and anterior segment of the eye21
- Dry eyes can also develop in patients treated with busulfan and nitrosourea (alkyl sulfonate agents)22
- 5-FU23 and docetaxel24 can cause stenosis of the punctum and tear drainage system
- 5-FU patients can also develop excessive lacrimation with cicatricial eyelid malpositioning3
- IV doxorubicin is also sometimes associated with excessive lacrimation3
- Ptosis can occur with long term corticosteroid use25
- Chemotherapy can cause:
1. Chemical conjunctivitis:
- Main reported symptom is conjunctivitis occurring with the initiation of therapy and resolves usually two weeks of treatment cessation3
- Chemotherapeutic agents associated with this side effect include:
- Cyclophosphamide
- Ifosfamide
- Nitrosoureas
- Cytosine arabinoside
- Doxorubicin
- Methotrexate
- Deoxycoformycin
- Mitomycin3
2. Infective conjunctivitis (bacterial or viral)
- Long term use of corticosteroids can cause immunosuppressive effects which facilitate opportunistic eye infections26
- Infective conjunctivitis is sometimes seen after use of:
- Methotrexate
- Carmustine
- Epirubicin
Chemotherapy damage to the cornea can be broadly divided into:
- Keratitis is a common symptom following treatment with chemotherapeutic agents such as:
- Chlorambucil
- Cyclophosphamide
- Methotrexate
- Nitrosoureas
- 5-FU
- Deoxycoformycin21
- Cytosine arabinoside can cause punctate corneal opacities and keratitis (acutely after therapy) and generally resolves within four weeks after completion of therapy3
- Isotretinoin and tretinoin particularly affect the tear film and can cause severe dry eye.
| Clinical tip: Use of fluorescein drops can reveal punctate epithelial staining suggestive of dry eye syndrome |
2. Corneal Hypothesia:
- Vincristine and Vinblastine can cause corneal hypoesthesia27. Prolonged hypothesia predisposes the cornea to ulceration and secondary infection.
| Clinical tip: Use of a rolled corner of tissue to lightly touch the cornea of the patient from a lateral side of each eye can be used to reveal if corneal sensation is compromised. |
3. Corneal Infections:
Corticosteroids can cause immunosuppression leading to keratitis and corneal ulcers, in particular herpetic keratitis3 classically causing a dendritic ulcer (branch-like pattern) with fluorescein staining.
- Prednisone therapy is associated with cataract formation1
- Systemic, inhaled, topical and skin steroid formulations3 can all cause this side effect.
- Tamoxifen21, mitomycin C3 and busulfan28 have all also been associated with cataract formation.
- Certain groups such as diabetics, the elderly and those exposed to radiation therapy to the orbit are more predisposed to cataract formation.
| Clinical Tip: Assessment of the red reflex with a direct ophthalmoscope is the most sensitive way of appreciating a cataract. Steroid induced cataracts are often located posteriorly in the lens (so called posterior subcapsular) and can be seen a central irregularity in the red reflex. |
UVEA (IRIS, CILIARY BODY and CHOROID)
- Glaucoma can develop due to an increase in intraocular pressure secondary to corticosteroid use. Generally therapy for at least two weeks is needed for the increase in pressure to occur3 and this is uncommon.
- Factors associated with an increased risk of damage from corticosteroid drugs are:
- Older age
- Family History of glaucoma
- Increased duration and dose of treatment29
| Clinical Tip: Patients on long term high dose steroids should have their intraocular pressure (IOP) measured at their optometrist and referred to a specialist if appropriate. |
- Studies have not reported any scleral complications when systemic chemotherapeutic agents are given3
- However, mitomycin C given as a topical adjunct treatment for ocular surface tumors, may lead to:
- Scleral ulceration
- Scleritis
- Scleral calcification21
OPTIC NERVE and RETINA
Nitrosoureas:
- The following complications have been reported after systemic therapy with nitrosoureas:
- Retinal hemorrhages
- Cotton wool spots
- Optic disc edema30
- Intracarotid infusion of nitrosoureas have been implicated in optic neuritis and atrophy31
Other drugs:
- Intra-carotid infusion of cisplatin can lead to visual loss from severe retinal and/or optic nerve ischemia, pigmentary retinopathy or exudative retinal detachment32
- Intrathecal methotrexate has been reported to cause optic nerve atrophy, optic neuropathy, retinal pigment changes and retinal edema33
- Corticosteroids can result in the development of pseudotumor cerebri and associated nerve swelling as well as retinal infections due to immunosuppression3
- Vincristine and Vinblastine may lead to visual loss and double vision secondary to optic neuropathy, optic atrophy and cranial nerve palsies27
- 5-FU can also result in cranial nerve palsies21
- Optic nerve damage can result from fludarabine, cyclosporine, paclitaxel, nitrogen mustards and intrathecal cytosine arabinoside3
ORBITAL BONE and soft tissues
- Intra-carotid cisplatin with intravenous etoposide may produce visual loss secondary to orbital inflammation and optic nerve ischemia34
- 5-FU and methotrexate therapy can lead to clinically significant periorbital edema3
- Corticosteroids can also cause mild protrusion of the globe (exophthalmos)35
- Cyclosporine can cause paralysis of eye muscles36 while vincristine can do so through cranial nerve palsy27
