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Partial thickness subfoveal hole in a patient treated with tamoxifen: a case report and review of the literature



We describe a patient presenting with a partial thickness subfoveal hole in the right eye after tamoxifen treatment for breast cancer.

Case presentation

A 76-year-old Caucasian female presented with a 1-day history of acute central scotoma and blurry vision in the right eye. The patient had been receiving oral tamoxifen for 5 years as adjuvant treatment for stage I lobular breast cancer. Her past ocular history was significant for complete, uneventful, and bilateral posterior vitreous detachment. Clinical examination and optical coherence tomography revealed a new, partial thickness subfoveal hole sparing the inner retinal layers. Observation was recommended. At the last follow-up examination, 1 year after the initial presentation, the subfoveal hole remained stable and visual acuity remained stable.


Tamoxifen has been associated with a plethora of ophthalmic adverse events, including macular holes, some of which are partial thickness subfoveal holes. Holes with this almost unique morphology are uncommon, and eye care professionals should be aware of this association given the frequency of tamoxifen use, as well as the low success rate of surgical repair with pars plana vitrectomy.

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Tamoxifen is a selective estrogen receptor modulator (SERM) used as adjuvant endocrine therapy for hormone receptor-positive breast cancer [1]. Previously reported ocular side effects include retinal crystals, optic neuritis, macular edema, dry eye, and cataracts [1, 2]. The retinal crystals used to be one of the classic ocular complications of tamoxifen in patients treated with 100 mg daily. Fortunately, these crystals have now become less common thanks to the protocols that recommend treatment with up to 20 mg/day for no more than 5 years [2]. Aside from these side effects, outer macular holes secondary to tamoxifen use have also been reported, and the pertinent literature is summarized in Table 1. Macular holes are an uncommon adverse event that can occur with tamoxifen, a commonly used drug.

Table 1 Summary of tamoxifen-related macular hole case reports in the current literature

Case presentation

A 76-year-old Caucasian female presented with a 1-day history of acute central scotoma and blurry vision in the right eye. She denied trauma, strenuous physical activity, or Valsalva-like maneuvers around the symptom onset. Her ocular history was notable for remote, previously documented, bilateral posterior vitreous detachment (PVD) without vitreomacular traction. The past medical history was significant for stage I lobular breast cancer, diagnosed and surgically resected. Following lumpectomy and postoperative radiation, the patient was on adjuvant oral tamoxifen (20 mg daily, total dose 36.5 g) for 5 years. The patient was no longer taking tamoxifen at the time of presentation.

On examination, her best-corrected visual acuity was 20/40 OD and 20/25 OS. The anterior segment examination demonstrated bilateral 1+ nuclear sclerotic cataracts. On fundus examination, the right eye demonstrated a PVD, a pink optic nerve with cup/disc ratio of 0.3, normal vessels, and abnormal foveal reflex in the right eye. Infrared imaging and optical coherence tomography (OCT) of her right eye (Fig. 1) showed a partial thickness subfoveal hole with total disruption of the ellipsoid zone. The examination and OCT of the left eye was essentially normal. The patient was followed closely and the subfoveal cyst remained unchanged on OCT. At the latest follow-up visit, 1 year after the initial presentation, the best-corrected visual acuity in the right eye was 20/30 and there were no anatomic changes on OCT imaging (Fig. 2). OCT of the left eye at latest follow-up was essentially normal (Fig. 3).

Fig. 1
figure 1

Near infrared image (A) of the right eye showing a hyporeflective round lesion in the fovea. Optical coherence tomography of the same eye (B) demonstrating a partial thickness, outer retinal hole with ellipsoid zone loss. Note that the inner retinal layers are preserved. The patient had a history of posterior vitreous detachment with no signs of vitreomacular traction in the vitreomacular interface

Fig. 2
figure 2

Near infrared image (A) of the right eye at latest follow-up visit. Optical coherence tomography (B) showed no anatomic changes since the initial presentation

Fig. 3
figure 3

Near infrared image (A) of the left eye at latest follow-up visit. Optical coherence tomography (B) of the left eye was essentially normal

Discussion and conclusions

Previous case reports suggest an association between tamoxifen use and macular hole development. Cronin et al. [3] found that the risk for macular hole development was significantly higher in women treated with tamoxifen compared with the control group of the same age (4.12% versus 0.82%, p = 0.0001). Although most tamoxifen-related macular holes have the typical foveal configuration on OCT, some of them do not. Gualino et al. [4] first published two cases of tamoxifen-retinopathy associated with outer foveal cysts and photoreceptor disruption, while the inner retinal layers were spared. One year later, Martine et al. [5] reported a similar case and described the findings as “large, foveolar pseudo-cyst.” Since then, other authors have shared similar findings that, in some cases, were bilateral [6]. It has previously been hypothesized that this, almost unique, configuration is secondary to a neurodegenerative process of the Müller cells [6].

A variety of surgical approaches for management of tamoxifen-related macular holes has been previously described. Bernstein and DellaCroce published a case of bilateral sequential macular holes in a 65-year-old female treated with tamoxifen [7]. The right macular hole only closed after the second pars plana vitrectomy (PPV) with C3F8, while the left eye’s hole remained open after a single PPV with gas. Torrell-Belzach et al. also found that PPV with inner limiting membrane (ILM) peeling and SF6 gas tamponade was unsuccessful [8]. One possible explanation is that the pathophysiology of these holes does not include the typical centrifugal traction on the surface of the retina that usually resolves upon removal of the ILM of the macula followed by gas tamponade [8].

The ocular side effects of tamoxifen have been known to ophthalmologists and optometrists alike for decades [912]. Nevertheless, the guidelines regarding appropriate screening and management of ocular toxicity due to tamoxifen are not as clear as seen in other medications. In a case of clinically significant ocular toxicity, the management can be challenging. For that reason, the patient’s expectations should be carefully adjusted after a lengthy conversation about the risks, benefits, and alternatives of each option [1]. In this case, the macular hole did not progress after discontinuation of the causative agent; as such, early surgical intervention was not needed.

Availability of data and materials

All data generated or analyzed during this study are included in this article.



Inner limiting membrane


Optical coherence tomography


Pars plana vitrectomy


Posterior vitreous detachment


Selective estrogen receptor modulator


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Authors and Affiliations



DM treated the subject and supervised the whole work. AS drafted the manuscript and constructed the table. GS and DM revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Dimosthenis Mantopoulos.

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This study adhered to the tenets of the Declaration of Helsinki and adhered with HIPAA. Retrospective review of patient data for this case report did not require IRB approval according to local guidelines.

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Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

DM reports consulting fees from Alimera Sciences. AS and GS declare no competing interests.

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Sohn, A., Sanchez, G. & Mantopoulos, D. Partial thickness subfoveal hole in a patient treated with tamoxifen: a case report and review of the literature. J Med Case Reports 16, 471 (2022).

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