Abstract
We report a case of a patient with treated breast cancer whose dilated fundus examination showed crystalline deposits in the central region of the macula. She was taking tamoxifen for secondary prevention. Optical coherence tomography revealed individual refractile deposits associated with intraretinal cysts in both eyes. Tamoxifen-related retinopathy was suspected. A decision to discontinue treatment with tamoxifen was considered but had to be taken in conjunction with the oncologist.
Background
Crystalline retinal deposits are known to occur in a number of systemic conditions, as well as in association with ingestion of certain drugs. Tamoxifen is a non-steroidal antioestrogen agent that is widely used to reduce the risk of developing recurrent breast cancer in high-risk patients.1 2 Tamoxifen-related crystalline retinopathy is a well-recognised entity.3 We describe a patient with features of tamoxifen-related retinopathy in whom the decision to discontinue treatment had to be considered and balanced with risk of recurrent disease.
Case presentation
A 52-year-old woman was referred to our ophthalmology department in 2014 after a review by her optometrist. Her best corrected visual acuity was 6/9 in both eyes. In 2008, she had been diagnosed with right-sided breast cancer. She underwent a wide local excision, postoperative radiotherapy to the affected breast and chemotherapy. Her tumour was a 21 mm, grade 2, invasive lobular carcinoma with extensive surrounding lobular carcinoma in situ. The tumour was oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative. Sentinel node biopsy was negative.
At the time of presentation, the patient was taking 20 mg of tamoxifen daily. This was ongoing for 5 years. A dilated examination of her fundi revealed fine, cream-coloured, refractile deposits around the fovea in both eyes (figure 1A). High-resolution, spatial domain optical coherence tomography (SD-OCT) imaging was undertaken. Intraretinal cysts and refractile deposits were seen in both maculae (figure 1B). The refractile deposits on OCT were presumed to be tamoxifen crystals whereas the cystic changes were deemed a consequence of structural damage to the inner retina. There were no other abnormalities noted on ophthalmic examination other than the retinal changes described. The patient was subjectively asymptomatic.
Figure 1.
(A) Colour fundus photograph of right eye showing multiple, small, yellow, refractile deposits on the macula, (B) optical coherence tomography of the right eye showing intraretinal cysts and deposits in the inner retina.
In view of the likelihood of progressive retinopathy, it was felt that a decision either to stop or continue treatment with tamoxifen would have to involve her oncologist and be balanced with the risk of tumour recurrence. An opinion was therefore sought and further review planned.
Outcome and follow-up
For the patient described in this case, treatment was discontinued with the patient's informed consent, by her oncologist, on the grounds of a significant disease-free period. After 6 months, there was no significant change in the retina of both eyes and vision was stable.
Discussion
Ocular toxicity secondary to high-dose (240–320 mg/day) tamoxifen was first described in 1978 by Kaiser-Kupfer and Lippman.4 It was later found that even smaller doses (20–40 mg/day) of tamoxifen can cause ocular side effects, although the changes may be less extensive.5 6 Tamoxifen ocular toxicity can result in reduced vision through keratopathy, cataract, crystalline retinal deposits associated with macular oedema and optic neuritis.4–8 The incidence of tamoxifen-related ocular toxicity among patients taking low-dose tamoxifen (20 mg/day) has been reported as ranging from 6.3%6 to 12%8 in two prospective studies.
Total cumulative dose of tamoxifen and duration of treatment are believed to be the main factors associated with increased incidence of ocular toxicity.8 However, there is much variation in the literature regarding ‘safe’ cumulative doses and ‘maximum’ duration of treatment.5 9 It has been suggested that screening for tamoxifen-related ocular toxicity is not required in patients who are on a low dose or who have been on treatment for a short duration of time.9 10 A total cumulative dose of less than 23.7 g has been reported as being safe by one study.9 Our patient had received a significant cumulative dose of tamoxifen—amounting to 40 g over a period of 5.5 years.
Discontinuation of tamoxifen may not cause regression of retinal deposits.5 6 However, other changes, such as keratopathy and macular oedema, have been reported as being reversible.5 6 8
Clinicians should be aware of tamoxifen-related ocular toxicity and should perhaps discuss the risk when starting treatment. Patients should also be advised to seek prompt ophthalmic review if there are any ocular or visual concerns. A multidisciplinary approach is needed to appropriately manage affected patients.
Learning points.
Ocular toxicity secondary to tamoxifen can present with reduced vision through keratopathy, cataract, crystalline retinal deposits associated with macular oedema and optic neuritis.
Even small dose (20–40 mg/day) tamoxifen can cause ocular side effects.
The incidence of ocular toxicity rises with increasing total cumulative dose of tamoxifen and duration of treatment.
Patients should be warned about the risks of tamoxifen-related ocular toxicity on initiation.
Patients on tamoxifen should be promptly referred to the ophthalmological team should there be any ocular symptoms.
Footnotes
Contributors: TB collected data and drafted the article. ZIC identified and managed the case and revised the paper. He is the guarantor.
Competing interests: None declared.
Patient consent: Obtained.
Provenance and peer review: Not commissioned; externally peer reviewed.
References
- 1.Fisher B, Costantino JP, Wickerham DL et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998;90:1371–88. 10.1093/jnci/90.18.1371 [DOI] [PubMed] [Google Scholar]
- 2.Fisher B, Costantino JP, Wickerham DL et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 2005;97:1652–62. 10.1093/jnci/dji372 [DOI] [PubMed] [Google Scholar]
- 3.Nadim F, Walid H, Adib J. The differential diagnosis of crystals in the retina. Int Ophthalmol 2001;24:113–21. 10.1023/A:1021189215498 [DOI] [PubMed] [Google Scholar]
- 4.Kaiser-Kupfer MI, Lippman ME. Tamoxifen retinopathy. Cancer Treat Rep 1978;62:315–20. [PubMed] [Google Scholar]
- 5.Nayfield SG, Gorin MB. Tamoxifen-associated eye disease: a review. J Clin Oncol 1996;14:1018–26. [DOI] [PubMed] [Google Scholar]
- 6.Pavlidis NA, Petris C, Braissoulis E et al. Clear evidence that long-term, low dose tamoxifen treatment can induce ocular toxicity. A prospective study of 63 patients. Cancer 1992;69:2961–4. 10.1002/1097-0142(19920615)69:12<2961::AID-CNCR2820691215>3.0.CO;2-W [DOI] [PubMed] [Google Scholar]
- 7.Gianni L, Panzini I, Li S et al. Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer: results from International Breast Cancer Study Group trials. Cancer 2006;106:505–13. 10.1002/cncr.21651 [DOI] [PubMed] [Google Scholar]
- 8.Noureddin BN, Seoud M, Bashshur Z et al. Ocular toxicity in low-dose tamoxifen: a prospective study. Eye (Lond) 1999;13(Pt 6):729–33. 10.1038/eye.1999.217 [DOI] [PubMed] [Google Scholar]
- 9.Tang R, Shields J, Schiffman J et al. Retinal changes associated with tamoxifen treatment for breast cancer. Eye (Lond) 1997;11(Pt 3):295–7. 10.1038/eye.1997.64 [DOI] [PubMed] [Google Scholar]
- 10.Heier JS, Dragoo RA, Enzenauer RW et al. Screening for ocular toxicity in asymptomatic patients treated with tamoxifen. Am J Ophthalmol 1994;117:772–5. 10.1016/S0002-9394(14)70321-6 [DOI] [PubMed] [Google Scholar]