Case report: Letrozole-induced central serous chorioretinopathy
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Central serous chorioretinopathy is a common chorioretinal disease characterized by a buildup of subretinal fluid at the macula caused by abnormalities of the retinal pigment epithelium pump dysfunction and choroidal circulation.
Fluid leaks from the choroidal circulation through hyperpermeable areas of retinal pigment epithelium (RPE) and accumulates in the subretinal space. Central serous chorioretinopathy (CSCR) predilection is higher in men aged 20 to 50years but may occur in women or individuals at an older age. Aromatase inhibitors (AIs) such as anastrozole, letrozole and exemestane have been increasingly prescribed to postmenopausal breast cancer patients as adjuvant endocrine therapy to truncate the ocular side effects of tamoxifen, which is commonly used in breast cancer treatment.
Source: Arnav Saroya, MS, Dhivya Ashok Kumar, MD, FRCS, FICO, FAICO, and Amar Agarwal, MS, FRCS, FRCOphth
Case summary
A 65-year-old woman diagnosed with breast carcinoma and treated with oral letrozole presented with diminution of vision in both eyes for 2 months. Best corrected visual acuity was 2/60 in the right eye and 6/24 in the left eye. On anterior segment examination, age-related cataract nuclear sclerosis grade 2 was present in both eyes. Fundus evaluation showed fluid accumulation suggestive of central serous retinopathy in the foveal region (Figure 1), and spectral domain OCT of the right eye showed subretinal fluid (SRF) at the macula (Figure 2). Fundus fluorescein angiography demonstrated ink blot leak suggestive of CSCR (Figure 3). Based on the patient’s history and ruling out all other causes, a diagnosis of letrozole-induced CSCR was made. The patient was advised to stop systemic letrozole after consultation with the oncology department. Two months later, an increase in SRF was noted (Figure 4). An intravitreal injection of ranibizumab 0.5 mg/0.05 mL was given in the right eye. One month after that (Figure 5), SRF was not resolved, and the patient was advised to have focal laser in the right eye. One month after focal laser, a reduction in SRF was noted.
Pathogenesis of CSCR
Hyperpermeability, thickening and congestion of the choroid result in impairment of the function of RPE, which forms the outer blood-retina barrier. Loss of integrity in this barrier leads to the accumulation of SRF, mainly affecting the macula and leading to marked central vision loss. Factors such as steroid use, psychosocial stress, hypertension and pregnancy have been implicated in acute CSCR. Drug-induced CSCR is also well established, but treatment with AIs leading to CSCR is limited to only a few case reports.
Letrozole-induced CSCR
Letrozole is an aromatase inhibitor, which acts by inhibiting the action of the enzyme aromatase, which converts androgens into estrogens by a process called aromatization. As breast tissue is stimulated by estrogens, decreasing their production is a way of suppressing recurrence of the breast tumor tissue, which is the role of letrozole. AIs such as letrozole are well known for their ocular side effects, including dryness, cataract, crystalline retinopathy and macular edema. Letrozole is also commonly used in infertility treatment. In recent years, AIs have been increasingly prescribed to postmenopausal breast cancer patients as adjuvant endocrine therapy, sometimes after 2 to 3 years of tamoxifen treatment. Estrogen receptors, namely alpha and beta, are expressed in the RPE, neurosensory retina and choroid. So estrogen, which has a neuroprotective effect in the retina, will be lost by inhibitors of estrogen synthesis such as AIs.
Management of CSCR
There have been various methods of managing noncomplicated CSCR, including controlling blood pressure, reducing stress and stopping steroids. The majority of cases will resolve by observation and symptomatic treatment. However, long-standing cases need intervention. A study by Sivaranjani and colleagues suggested the use of focal laser in patients who did not respond to ranibizumab. A study by Kim and colleagues suggested the use of intravitreal ranibizumab injection for acute CSCR and showed resolution of neurosensory detachment compared with observation alone. There has been a report in which letrozole-bevacizumab combination therapy had a synergistic effect on tumor control.
Conclusion
We report a rare case of letrozole-induced CSCR in a breast cancer postmenopausal woman who did not respond to ranibizumab but responded to focal laser. It may be prudent for oncologists and radiotherapists to have an ophthalmology consultation for their patients on AIs to understand whether this is indeed rare or underreported. Drug-induced CSCR is not an uncommon entity, and many cases resolve spontaneously after drug cessation. However, rarely, intervention may be needed.
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- For more information:
- Amar Agarwal, MS, FRCS, FRCOphth, director of Dr. Agarwal’s Eye Hospital and Eye Research Centre, is the author of several books published by SLACK Books, sister company of Healio publisher Ocular Surgery News, including Phaco Nightmares: Conquering Cataract Catastrophes, Bimanual Phaco: Mastering the Phakonit/MICS Technique, Dry Eye: A Practical Guide to Ocular Surface Disorders and Stem Cell Surgery and Presbyopia: A Surgical Textbook. He can be reached at aehl19c@gmail.com; website: www.dragarwal.com.
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