Sir,

Clomiphene citrate (CC) is a selective estrogen receptor modulator mostly used for treatment of infertility associated with polycystic ovarian disease.1 Unlike Tamoxifen, which is also a selective estrogen receptor modulator, maculopathy has not been reported in association with CC in previous reports.2, 3, 4

Case report

A 33-year-old woman developed progressive visual impairment and headaches within the last 6 months. Her visual acuity was 20/200 OU. Color vision was normal. Fundus examination showed atrophic changes at the macula (Figure 1). She had no prior history of systemic or familiar retinal disease, and her medical records confirmed that she had 20/20 vision OU 3 years ago.

Figure 1
figure 1

Color fundus appearance of the patient showing oval-shaped macular atrophy in both eyes.

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She denied usage of systemic agents that may induce maculopathy, but reported using CC (100 mg/day, 5 days per cycle). She kept using CC by her own for 3 years without visiting her gynecologist for infertility treatment. Cranial MRI showed no intracranial pathology. Fluorescein angiography (FA) revealed RPE defects with perifoveal macular staining (Figure 2). The headaches subsided within 3 months after cessation of CC; however, visual impairment and macular changes were persistent during a 2-year follow-up.

Figure 2
figure 2

FA shows the central area of retinal pigment epithelial atrophy giving a bull’s eye appearance to the macula in both eyes. There was no leakage from these areas at the later phases.

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Discussion

CC has potential systemic side effects and ≥6 cycles of therapy is not usually recommended for ovulation induction.1 Several dose-related ocular side effects have been defined, such as blurred vision, scotomata, diplopia, photophobia, temporary visual impairment, and retinal vein occlusion.2, 3 Although these adverse ocular effects generally disappear within a few days to weeks following discontinuance of therapy, shimmering after-images (palinopsias) and photophobia have been reported to be symptomatic in three cases for 2–7 years.3

Maculopathy associated with CC was not reported in previous series. Our case was taking CC by her own for an overextended period and developed irreversible visual impairment with maculopathy. Although CC has a similar molecular structure to tamoxifen,4 CC-associated retinopathy differs from tamoxifen retinopathy as there are no blocking crystals in FA, but atrophic maculopathy. Our case indicates that CC may induce irreversible retinal damage and visual deterioration if used for an overextended period.