Madhu Nagar, Dr Dimitrios K Tsouris and Sabitha Bandi describe an unusual manifestation of ocular adverse response to tamoxifen
It is well recognised that chemo-therapy and radiotherapy for cancer may be associated with vascular complications, though it is not clear whether these complications are as a result of drugs, malignancy itself or some other unrelated factor.
We report here on an atypical case of retinopathy associated with tamoxifen therapy for breast carcinoma.
CASE REPORT
A 34-year-old female, diagnosed with right breast carcinoma in October 1999, was started on tamoxifen (20mg daily) after wide local excision. In April 2001, due to recurrence, she underwent a right radical mastectomy and radiotherapy.
She was referred by her optometrist in June 2003 because of abnormal retinal findings during routine ophthalmic examination. By then she had received a total dose of 26g of tamoxifen over a 44-month period.
OPHTHALMIC EXAMINATION
Uncorrected visual acuities were 6/5 in both eyes. Anterior segment biomicroscopy of both eyes was unremarkable. Applanation tonometry showed intraocular pressures of 18 mmHg and 16 mmHg for the right and left eye respectively. Colour vision was normal, but the Amsler chart revealed an area of central distortion inferiorly for the right eye.
Dilated fundoscopy revealed bilateral healthy optic discs and maculae. The only abnormal finding was a parafoveal cotton-wool spot with neighbouring superficial, retinal hemorrhage in the right posterior pole. These findings disappeared after cessation of tamoxifen. Blood tests were as in Table 1.
Detected values | Normal values | |
Haematocrit | 0.380 | |
Platelet | 200x109/L | |
Hb | 12.9 g/dl | |
Cardiolipin abs (IgG) | 1.5 GPLU/ml | 0-10 GPLU/ml |
Cardiolipin abs (IgM) | 2.6 MPLU/ml | 0-9 MPLU/ml |
Prothrombin time | 10.8 sec | 9.5-12.5 sec |
Activated partial tromboplastin time | 26.9 sec | 22-32 sec |
APTTSP | 33.2 sec | 25-36 sec |
Activated protein C resistance | 2.5 ratio | 2-2.8 |
Antithrombin III | 0.8 U/ml | 0.73-1.33 U/ml |
DRVVT | 1.00 ratio | 0.8-1.2 |
Protein C chromogenic | 1.00 U/ml | 0.71-1.63 U/ml |
Prothrombin gene mutation | Not detected | |
Protein S free antigen | 0.9 U/ml | 0.6-1.28 U/ml |
Fibrinogen | 2.1 g/l | 1.5-4.5 g/l |
Cryoprotein screen | Not detected | |
Rheumatoid factor | 4.8 lU/ml | 0-20 lU/ml |
Antinuclear ab | Negative | |
Anti mitochrondial ab | Negative | |
Anti smooth muscle ab | Negative | |
Gastric parietal cell ab | Negative | |
C3 | 0.90 g/l | 0.60-1.27 g/l |
C4 | 0.22 g/l | 0.15-0.45 g/l |
ANCA screen | Negative |
Table 1. Investigations
DISCUSSION
Tamoxifen is an antioestrogen drug used widely in the management of oestrogen-dependent metastatic breast carcinoma. It is generally well-tolerated, apart from certain well-documented side effects like thromboembolic disease and endometrial carcinoma. Ocular adverse effects reported include keratopathy, optic neuritis, macular oedema and superficial white refractile deposits that appeared to be in the inner layers of the retina.1
What is interesting in our case is the presence of ocular microvasculopathy in the form of a cotton-wool spot and retinal haemorrhage. Thromboembolism and vascular toxicity have been reported with increasing frequency after chemotherapy and hormone therapy.2 It has also been reported that pre-menopausal patients who received chemotherapy and tamoxifen had significantly more venous complications (2.8 per cent vs 0.8 per cent, P=0 .03) and arterial thrombi (1.6 per cent vs 0.0 per cent, P= 0.004) than patients who received chemotherapy alone.3
The data seem to support the hypothesis that tamoxifen may be responsible for vascular pathology, which in our patient is visible in the retina. All investigations were within normal limits and there was no obvious pathology or cause for thromboembolism or microvasculopathy. Hence, we conclude that the observed ischaemic changes (cotton-wool spot and haemorrhage in the parafoveal region of the right eye) represent a rare and unusual manifestation of tamoxifen retinopathy. Awareness of the ocular toxicity of tamoxifen is essential as prompt withdrawal can result in resolution of most of the complications.
Figure 1. Colour fundus photography (right eye): note atypical parafoveal cotton wool spot and superficial retinal haemorrhages | Figure 2. Fundus fluorescein angiogram of right eye (late phase): hyperfluorescent, juxtafoveal lesion due to leakage and choroidal masking due to retinal haemorrhage |
References
1 Kaiser-Kupfer MI, Lippman ME. Tamoxifen retinopathy. Cancer Treat Rep, 1978; 62:315-20.
2 Donald C. Doll, John W. Yarbro. Vascular toxicity associated with chemotherapy and hormonotherapy. Oncology, 1994, 6:345-350.
3 Thomas Saphner, Douglas C. Tormey, Robert Gray. Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. Journal of Clinical Oncology, 1991; 9: 286-94.
- Ophthalmologists Madhu Nagar, Dr Dimitrios K Tsouris, and Sabitha Bandi are based at the Clayton Eye Centre, Wakefield