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 Table of Contents  
Year : 2022  |  Volume : 2  |  Issue : 2  |  Page : 463-464

Tamoxifen maculopathy – A case with early optical coherence tomography changes

Pushpagiri Eye Institute, Department of Vitreo-Retinal Services, Secunderabad, Telangana, India

Date of Submission08-Sep-2021
Date of Acceptance18-Oct-2021
Date of Web Publication13-Apr-2022

Correspondence Address:
P Sai Kiranmayee
302, Vasavi Bhuvana Apartment, Srinagar Colony, Hyderabad - 500 073, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_2350_21

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Tamoxifen is an antiestrogen agent used as adjuvant therapy in breast carcinoma. Crystalline maculopathy due to tamoxifen toxicity, though rare, causes irreversible changes in the retina. High-resolution imaging like spectral-domain optical coherence tomography (SD-OCT) can detect early degenerating changes like crystalline deposits and cavitation in the retina. Early detection helps in the prevention of visual loss by prompt consideration in discontinuing or replacing the drug. Periodic screening with SD-OCT is essential as structural changes in the retina are noted even in asymptomatic patients receiving low-dose tamoxifen.

Keywords: Crystalline maculopathy, optical coherence tomography, tamoxifen toxicity

How to cite this article:
Kiranmayee P S, Kalluru V, Govindahari V. Tamoxifen maculopathy – A case with early optical coherence tomography changes. Indian J Ophthalmol Case Rep 2022;2:463-4

How to cite this URL:
Kiranmayee P S, Kalluru V, Govindahari V. Tamoxifen maculopathy – A case with early optical coherence tomography changes. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 May 18];2:463-4. Available from: https://www.ijoreports.in/text.asp?2022/2/2/463/342947

Tamoxifen is an antiestrogen agent used as adjuvant therapy in breast carcinoma after surgical resection. The first cases of tamoxifen retinopathy were described by Kaiser-Kupferin in 1978.[1] The early reports involved patients who had received high doses, but with current low-dose therapy (20–40 mg/day), retinal lesions are rare.

  Case Report Top

A 32-year-old woman was referred by an oncologist for ophthalmology evaluation as she was complaining of blurring of vision in both her eyes for 2 months. She underwent left radical mastectomy for breast carcinoma along with adjuvant chemotherapy and radiotherapy followed by hormonal therapy. She was on tamoxifen 20 mg daily for 3.5 years and the cumulative dose was 25.5 g. On examination, Snellen's best-corrected visual acuity (BCVA) was 6/9 and 6/6 in the right and left eyes, respectively. The color vision measured using the Ishihara chart was normal in both eyes. The intraocular pressure was 14 mmHg in both eyes. The anterior segment and pupillary reflex were normal. The fundus examination revealed fine, yellow-white refractile deposits in the parafoveal area [Figure 1]a and [Figure 1]b. The optic disk and peripheral retina were normal. The spectral-domain optical coherence tomography (SD-OCT) imaging demonstrated hyperreflective deposits in the ganglion cell layer in both eyes along with hyporeflective spaces in the outer nuclear layer [Figure 1]c and [Figure 1]d. Ellipsoid zone (EZ) disruption was noted in the right eye which accounted for the BCVA [Figure 1]c. The fundus fluorescein angiography did not demonstrate any leakage akin to idiopathic parafoveal telangiectasia. As the retinal changes were in favor of tamoxifen toxicity, it was discontinued, and letrozole, a nonsteroidal aromatase inhibitor, was started in consultation with the oncologist. The patient was reviewed 1 year after the discontinuation of tamoxifen. The changes in the SD-OCT remained the same with neither progression nor regression.
Figure 1: (a) and (b) Shows fundus photos of the right and left eyes with fine yellow-white refractile deposits in the parafoveal area (black arrow). (c) and (d) Shows SD-OCT of both eyes with hyperreflective deposits in the ganglion cell layer along with hyporeflective spaces in the outer nuclear layer (arrow). Ellipsoid zone (EZ) disruption was noted in the right eye (arrow-head)

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  Discussion Top

Crystalline retinal deposits have been observed in systemic and ocular conditions such as oxalosis, cystinosis, hyperornithinaemia, Sjogren-Larsson syndrome, calcified macular drusen, and idiopathic parafoveal telangiectasia.[2] Drugs such as tamoxifen also lead to crystalline retinopathy along with the development of vortex keratopathy, cataract, optic neuritis, and pseudo-cystoid spaces.[1],[3],[4] The pseudo-cystoid cavitary lesions can be differentiated from cystoid macular edema by the absence of leakage on fundus fluorescein angiography and a normal to reduced thickness on SD-OCT. The amphiphilic nature of tamoxifen leads to oxidative cell damage by binding to polar lipids similar to other drugs such as chloroquine, amiodarone, and thioridazine which are structurally similar.[5]

The neural retina and pigment epithelium have estrogen receptors like breast tissue.[6] Tamoxifen inhibits glutamate-aspartate transporters present in pigment epithelial cells and Muller cells resulting in glutamate excess, which causes formation of cavitary spaces due to Muller cell dysfunction and neural apoptosis.[7] The crystalline refractile deposits in tamoxifen retinopathy occur due to axonal degeneration of the nerve fiber layer in the parafoveal area. A similar pathological cascade has been implicated in idiopathic parafoveal telangiectasia.[8] The acute form of tamoxifen retinopathy which presents with retinal edema and optic disk swelling is reversible,[9] unlike the irreversible crystalline maculopathy. Crystal formation represents one of the early manifestations of Muller cell damage while cavitation occurs at a later stage representing degeneration of Muller cell architecture. Isolated crystal formation in the absence of other structural changes on SD-OCT may not warrant a change in medication but the presence of cavitary changes prompts a consult with the treating oncologist to consider discontinuation of tamoxifen.[4]

High-resolution imaging such as SD-OCT help in detecting early and subtle retinal changes such as crystals and cavitation due to tamoxifen toxicity in the absence of any symptoms.[10] These are important signs for us to consider to prevent further irreversible damage. It is imperative to note the persistence of OCT changes despite the cessation of tamoxifen denoting irreversibility of the outer retinal degeneration. While the initial descriptions reported toxicity at a high dose (240–320 mg/day) of tamoxifen,[1] our patient demonstrated early changes at a much lower dose of 20 mg/day (cumulative dose 25.5 g) highlighting the need for retinal imaging on a periodical basis. The visual acuity in our patient was stable and there was no deterioration due to early detection and discontinuation of tamoxifen.

  Conclusion Top

Tamoxifen retinopathy, though rare, causes irreversible neuro-retinal degeneration, and hence, warrants periodic fundus examination. SD-OCT is useful in detecting early retinal changes and guides management protocols with regard to drug continuation. Understanding subtle changes on SD-OCT and subsequent liaison with the treating oncologist results in early diagnosis and prevention of progressive vision loss.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Kaiser-Kupfer MI, Lippman ME. Tamoxifen retinopathy. Cancer Treat Rep 1978;62:315-20.  Back to cited text no. 1
Nadim F, Walid H, Adib J. The differential diagnosis of crystals in the retina. Int Ophthalmol 2001;24:113-21.  Back to cited text no. 2
Salomao SR, Watanabe SE, Berezovsky A, Motono M. Multifocal electroretinography, color discrimination and ocular toxicity in tamoxifen use. Curr Eye Res 2007;32:345-52.  Back to cited text no. 3
Doshi RR, Fortun JA, Kim BT, Dubovy SR, Rosenfeld PJ. Pseudocystic foveal cavitation in tamoxifen retinopathy. Am J Ophthalmol 2014;157:1291-8.  Back to cited text no. 4
Toler SM. Oxidative stress plays an important role in the pathogenesis of drug-induced retinopathy. Exp Biol Med (Maywood) 2004;229:607-15.  Back to cited text no. 5
Eisner A, Luoh SW. Breast cancer medications and vision: Effects of treatments for early-stage disease. Curr Eye Res 2011;36:867-85.  Back to cited text no. 6
Bringmann A, Pannicke T, Grosche J, Francke M, Wiedemann P, Skatchkov SN, et al. Muller cells in the healthy and diseased retina. Prog Retina Eye Res 2006;25:397-424.  Back to cited text no. 7
Kaiser-Kupfer MI, Kupfer C, Rodrigues MM. Tamoxifen retinopathy. A clinicopathologic report. Ophthalmology 1981;88:89-93.  Back to cited text no. 8
Li J, Tripathi RC, Tripathi BJ. Drug -induced ocular disorders. Drug Saf 2008;31:127-41.  Back to cited text no. 9
Chung H, Kim D, Ahn SH, Kim JG, Lee JY, Lim JY, et al. Early detection of tamoxifen-induced maculopathy in patients with low cumulative doses of tamoxifen. Ophthalmic Surg Lasers Imaging 2010:1-5. doi: 10.3928/15428877-20100215-06.  Back to cited text no. 10


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