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| ORIGINAL ARTICLE |
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| Year : 1995 | Volume
: 43
| Issue : 1 | Page : 23-26 |
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Ocular toxicity of tamoxifen
G Chandra Sekhar, Rukmini Nagarajan
L.V. Prasad Eye Institute, Hyderabad, India
Correspondence Address:
G Chandra Sekhar
L.V. Prasad Eye Institute, Road No. 2, Banjara Hills, Hyderabad 500 034
India
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 8522365 
Tamoxifen is an antioestrogen drug used widely in the management of oestrogen-dependant metastatic breast carcinoma. A number of ocular complications have been described secondary to tamoxifen therapy. We report two patients, one of whom had superior ophthalmic vein thrombosis and the other who had painful proptosis and acute angle-closure glaucoma with choroidal detachment secondary to tamoxifen therapy, both of which have not been reported earlier. In both patients the signs and symptoms resolved rapidly after the discontinuation of tamoxifen therapy. Awareness of the ocular toxicity of tamoxifen is essential as prompt withdrawal can result in resolution of most of the complications. Keywords: Choroidal detachment - Secondary glaucoma - Superior ophthalmic vein - Thrombosis - Tamoxifen.
How to cite this article:
Sekhar G C, Nagarajan R. Ocular toxicity of tamoxifen. Indian J Ophthalmol 1995;43:23-6 |
Tamoxifen is widely used in the treatment of estrogen- dependent metastatic breast carcinoma[1] and other malignant tumours that express estrogen receptors like ovarian cancer, pancreatic cancer, or malignant melanoma.[2][3][4] Its prophylactic use against breast cancer in high-risk premenopausal women is under investigation. Though tamoxifen is considered the least toxic and the most potent agent in endocrine treatment, various ocular complications have been reported with its usage.[5][6][7][8][9][10]
The various manifestations of ocular toxicity produced with the use of tamoxifen include corneal opacity, bilateral macular oedema, yellow-white dots in the paramacular area, bilateral disc swelling with retinal haemorrhages and reduced visual acuity.[5][6][7][8][9][10]Most of these complications except yellow-white dots in the paramacular area have been reported to be reversible after the cessation of tamoxifen therapy. We report two complications arising with the use of tamoxifen - superior ophthalmic vein thrombosis in one patient, and, painful proptosis and acute angle-closure glaucoma with choroidal detachment in the other, both of which have not been recorded earlier in the literature.
| Case I | |  |
A 73-year-old female presented in January.1990 with proptosis in the right eye associated with redness, swelling of lids and occasional diplopia of 1 month duration. Her past history revealed right mastectomy in February 1988, excision of left intracranial meningioma in August 1988, cataract extraction with posterior chamber intraocular lens implantation in the right eye in August 1988 and, later, in the left eye in February 1989. On specific questioning, the patient denied any history of having subjective bruit. She was on oral tamoxifen 10 mg twice daily for the previous 2 years.
On examination, the best-corrected visual acuity was 6/9, J3 in the right eye and 6/6, Jl in the left. The right eye revealed an axial proptosis of 6 mm (Hertel's reading 21 mm and 15 mm with a bar reading of 109). There was minimal oedema of the lids with marked dilation of episcleral vessels and trace chemosis of conjunctiva [Figure:1A]. The motility was restricted in all directions of gaze. Anterior segment examination was unremarkable but for a posterior chamber pseudophakos in either eye. The intraocular pressure on applanation tonometry was 12 mm Hg in each eye. Fundus evaluation revealed 0.8:1 symmetrical cups with healthy neuroretinal rims bilaterally. There were dilated tortuous veins with single haemorrhage along the superior temporal vessels in the right eye. The CT scan showed marginal enlargement of the extraocular muscles on the right side along with a dilated superior ophthalmic vein [Figure - 2].
In view of this clinical picture, a dural cavernous fistula was suspected and the patient was referred for the opinion of a neuro surgeon. Evaluation by a neuro surgeon, neurologist and oncologist led to the suspicion of thrombosis of the superior ophthalmic vein, secondary to tamoxifen therapy. When oral tamoxifen was discontinued, the ocular signs and symptoms resolved completely within one week [Figure:1B]. A follow-up evaluation one month later and enquiry over phone 3 years later revealed that the patient was well and had no evidence of any ocular problems.
| Case 2 | | |
A 56-year-old female presented in August 1992 with symptoms of severe pain in and around the left eye associated with redness and prominence of the eye of 4 days's duration. She was evaluated by an ophthalmologist elsewhere and was started on timolol maleate 0.5% eye drops twice daily and oral acetazolamide 250 mg twice daily. Her records revealed that an intraocular pressure (IOP) of 28 mm Hg was recorded in the left eye and a proptosis was suspected. Past history revealed a left mastectomy for carcinoma of the breast in 1979, removal of a benign cyst from right breast in 1983 and cholecystectomy in 1987. She had been on oral tamoxifen 10 mg twice daily for the previous 12 years.
On examination, she had a best-corrected visual acuity of 6/7.5, J1 in the right eye and 6/9, J1 in the left. There was a left axial proptosis of 3 mm (Hertel's reading 15 mm and 18 mm with a bar reading of 100). The ocular movements were full. Anterior segment examination revealed mild conjunctival congestion in the left eye, clear corneas bilaterally, normal anterior chamber depth in the right eye and markedly shallow anterior chamber with peripheral iridocorneal touch in the left eye [Figure:3A]. The intraocular 0pressure on applanation tonometry was 15 mm Hg in the right eye and 25 mm Hg in the left eye. Fundus examination revealed blurred margins of the optic disc with hyperaemia on the left side. Echography and CT scan of the left orbit revealed normal orbital structures with a choroidal detachment in the left eye [Figure - 4]. A provisional diagnosis of secondary angle-closure glaucoma with choroidal detachment and proptosis in the left eye was made.
Tamoxifen was considered responsible for these ocular features and hence was discontinued. She was treated with topical betamethasone 0.1% eye drops and topical timolol maleate 0.5% eye drops twice daily, and oral acetazolamide was continued. An evaluation 3 days later revealed the patient to be much better symptomatically, though there was no change in the clinical picture, except for the reduction in IOP to 19 mm Hg in the left eye. Oral acetazolamide and timolol maleate were stopped and cyclopentolate 1% eye drops 3 times a day was advised. With this treatment over the next 10 days, the choroidal detachment settled, the anterior chamber deepened [Figure:3B] and the proptosis regressed completely. Subsequently, the patient had left episcleritis which required topical betamethasone 0.1% thrice daily and oral indomethacin 25mg, three times a day for 8 weeks. Later, she was on 0.1% topical bethamethasone one to two times a day for 3 months. Thereafter, all medications were stopped and she was asymptomatic. There was no proptosis, ocular motility was full, visual acuity was 6/6 in each eye, IOP was 15 mm in each eye and anterior segment and fundus were within normal limits.
| Discussion | | |
Tamoxifen is an antiestrogenic agent that provides effective palliative treatment in advanced breast cancer and can also be used as an adjunct in the treatment of estrogen-dependent breast tumours that express estrogen receptors.[1] Tamoxifen therapy has been considered the treatment of choice in these situations because of the relatively rare toxicity problems associated with its use. However, several sight-threatening complications have been reported with the use of tamoxifen.[5][6][7][8][9][10]
The reported complications with the use of tamoxifen like corneal opacities and macular oedema are usually dose-dependent, occur following long-term administration and are reversible after cessation of tamoxifen therapy.[10] It has been suggested that periodic ocular evaluations be done to detect these complications before visual deterioration occurs.[8],[10]Ashford[9] reported a case of bilateral optic disc swelling, retinal haemorrhages and decreased vision 3 weeks after starting tamoxifen therapy which completely reversed after discontinuing tamoxifen. This highlights the fact that tamoxifen toxicity can occur acutely and at low doses also.
The two complications reported here, due to tamoxifen toxicity, have not been reported in the literature till date. The first patient had all features of superior ophthalmic vein thrombosis. The cause and effect relationship in this case between tamoxifen and superior ophthalmic vein thrombosis was proved by the dramatic resolution of the problem when the drug was discontinued. The duration of tamoxifen therapy in this patient was more than 2 years at a dose of 20 mg daily.
The second case presented with proptosis and secondary angle-closure glaucoma after more than 12 years of treatment with tamoxifen at a dose of 20 mg daily. All efforts to identify an orbital pathology were futile. The combination of conjunctival congestion, choroidal detachment and proptosis could be attributed to venous outflow obstruction from the eye. As the CT scan with and without contrast did not demonstrate a dilated superior ophthalmic vein, the obstruction could possibly be in smaller venules resulting in choroidal effusion as well as proptosis. Choroidal effusion can result in shallow anterior chamber and iridocorneal touch due to forward movement of the lens. The intraocular pressure will depend on the balance between the reduced amount of aqueous secreted by the detached ciliary body on the one hand and reduced aqueous outflow because of the angle closure compounded by the raised episcleral venous pressure - a sequelae of venous outflow obstruction on the other hand. Cessation of tamoxifen therapy resulted in a rapid resolution of signs and symptoms in this patient.
In conclusion, we have presented two hitherto unrecorded ocular complications of tamoxifen therapy, namely superior ophthalmic vein thrombosis in one patient and painful proptosis with choroidal effusion and secondary angle-closure glaucoma in the other. The possibility of the latter event being also secondary to venous obstruction is discussed.
| References | | |
| 1. | Ingle JN. Additive hormonal therapy in women with advanced breast cancer. Cancer 53:766-777, 1984.  |
| 2. | Schwartz PE, Keating G, MacLusky N. Tamoxifen therapy for advanced ovarian cancer. Obstet Gynecol 59:583-588, 1982. |
| 3. | Tonnesen K, Kamp-Jensen M. Antiestrogen therapy in pancreatic carcinoma: A preliminary report. Eur J Surg Concol 12:69-70, 1986. |
| 4. | Meyskens FL Jr, Voakes JB. Tamoxifen in meta-static malignant melanoma. Cancer Treat Rep 64:171-173, 1980. |
| 5. | Kaiser-Kupfer ML, Lippman ME. Tamoxifen retinopathy. Cancer Treat Rep 62:315- 320, 1978. |
| 6. | Mc Keown CA, Swartz M, Blom J, et al. Tamoxifen retinopathy. Br J Ophthalmol 65:177-179, 1981. |
| 7. | Vinding T, Nielsen NV. Retinopathy caused by treatment with tamoxifen in low dose. Acta Ophthalmol 61:45-50, 1983. |
| 8. | Griffiths MF. Tamoxifen retinopathy at low dosage. Am J Ophthalmol 104:185-186, 1987. |
| 9. | Ashford AR, Donev I, Tiwati RP, et al. Reversible ocular toxicity related to tamoxifen therapy. Cancer 61:33-35, 1988. |
| 10. | Pavlidis NA, Petris C, Briassoulis, et al. Clear evidence that long-term, low dose tamoxifen treatment can induce ocular toxicity. Cancer 69:2961-2964, 1992. |
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]
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