SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN TAMOXIFEN RETINOPATHY—A CASE REPORT Sandhya Narayanan Nair, MS, Giridhar Anantharaman, MS, Mahesh Gopalakrishnan, FRCS, Jyothiprakash Vyas, MS
Purpose: To report spectral domain optical coherence tomography findings in a case of typical tamoxifen retinopathy. Methods: In this observational case report, a patient with tamoxifen retinopathy was imaged with spectral domain optical coherence tomography and fundus auto fluorescence. Results: Spectral domain optical coherence tomography showed numerous hyperreflective spots within the retina, mainly in the inner retinal layers in both the eyes. The external limiting membrane, the Inner Segment-Outer Segment junction, and the photoreceptors were not discernable at the fovea in the right eye. In the left eye, there was foveal atrophy with total loss of photoreceptors. The autofluorescent images showed macular hypofluorescence with foveal hyperfluorescence. Conclusion: Spectral domain optical coherence tomography demonstrated abnormalities in the outer retinal layers in tamoxifen retinopathy. There were also characteristic alterations in the autofluorescence pattern at the macula in tamoxifen retinopathy. RETINAL CASES & BRIEF REPORTS 7:128–130, 2013
SD-OCT showed numerous hyperreflective deposits at the macula mainly within the inner retinal layers (up to the outer plexiform layer). There was a large hyperreflective spike at the center of the fovea projecting into the vitreous. There was also foveal thinning in the right eye (macular thickness was 175 mm). The external limiting membrane, Inner Segment-Outer Segment junction, and the photoreceptors were not discernable at the fovea in the scan. There was mild macular edema nasal to the fovea in the right eye (Figure 2). In the left eye also there were many hyperreflective deposits at the macula in the inner retinal layers. Large deposits at the fovea slightly projecting into the vitreous were found. There was foveal atrophy in the left eye with total loss of photoreceptors (macular thickness was 170 mm in the left eye). Few cystoid spaces at the macula nasal to the fovea in the left eye were also found (Figure 3). Autofluorescent pictures of both eyes showed generalized reduction of autofluorescence at macula with increased autofluorescence at the fovea. The decreased fluorescence at the macula may be due to the absorption of fluorescent energy by the deposits and the increased fluorescence at the fovea may be because of the unmasking of retinal pigment epithelium lipofuschin secondary to foveal thinning. The foveolar spike in the right eye was hypofluorescent (Figure 4).
From the Giridhar Eye Institute, Kadavanthra, India. Case Report A 43-year-old woman presented with progressive worsening of vision in both eyes. In 2003, she was diagnosed with locally invasive pelvic fibromatosis. She underwent wide excision surgery twice, first in February 2003 and then in November of the same year. Postoperatively, she was given 20 mg per day of tamoxifen. However, the tumor recurred 5 months later, and it was deemed inoperable. She was given 23 cycles of radiotherapy and her tamoxifen dosage was increased to 200 mg per day. She received a cumulative dose of 500 g of tamoxifen, which was quite high. In February 2011, she presented to us with a 3-month history of progressive dimness of vision in both eyes. On examination, her Snellen visual acuity was 6/18 N8 in both eyes, and she had normal anterior segment and intraocular pressure. Dilated fundus examination showed numerous refractile crystals at the macula in both the eyes almost symmetrically (Figure 1). Spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence were performed in both eyes using Spectralis (Heidelberg Engineering, Heidelberg, Germany). In the right eye,
Discussion
The authors have no financial or conflicts of interest to disclose. Reprint requests: Sandhya Narayanan Nair, MS, Ponneth Temple Road, Kadavanthra, Cochin 682020, India; e-mail: [email protected]
Tamoxifen is an anti-estrogen drug used most commonly in the management of hormone receptor–positive 128
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129
Fig. 1. Colour fundus photographs with tamoxifen retinopathy showing refractile deposits at macula.
breast cancer. However, in our case, this was given for a recurrent locally invasive pelvic fibromatosis. Ocular complications are rare and occur in 0.6% of patients and include cataract, vortex keratopathy, optic neuritis, and retinopathy.1 In the literature, patients with tamoxifen retinopathy had a cumulative dose ranging from 6 to 81 g. However, more recent reports demonstrate maculopathies occurring at much lower cumulative doses (4.2–9.6 g).2 Up to 12% of patients taking 20 mg per day of tamoxifen develop retinal toxicity.3 The huge foveal deposit seen in this case is most probably because of the high cumulative dose of tamoxifen. There are also reports of tamoxifen retinopathy in male patients who were given tamoxifen for inoperable hepatocellular carcinoma.4 The pathogenesis
Fig. 2. Spectral domain optical coherence tomography of the right eye showing inner retinal deposits, foveal thinning, and the spike-like deposit at the fovea. The Inner Segment-Outer Segment junction could not be seen clearly.
Fig. 3. Spectral domain optical coherence tomography of the left eye showing cystoid spaces.
is thought to be increased accumulation of glutamate that leads to axonal degeneration (observed histopathologically). The crystals seen on fundus examination correspond to the degenerative products.5 Extensive deposits may result in macular edema and impaired visual acuity. Visual acuity may improve with the withdrawal of tamoxifen along with resolution of macular edema, but retinal deposits often do not regress.6 Gualino et al5 reported OCT findings in two cases of tamoxifen retinopathy, which showed foveal cystoid space, with interruption of the photoreceptor layer without increase in macular thickness that indicated atrophy of the retinal tissue in the fovea. Bourla et al7 showed macular cystoid spaces associated with fluorescein leakage in one patient and fluorescein leakage without cystoid space in another patient. Both patients
Fig. 4. Autofluorescent images of right and left eyes with tamoxifen retinopathy showing macular hypofluorescence and foveal hyperfluorescence. The foveal spike in the right eye was hypofluorescent.
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showed hyperreflective deposits in the inner retinal layers at the macula and periphery.7 Chung et al2 observed intraretinal cysts and focal disruptions of the photoreceptor transition lines on three-dimensional OCT of patients with tamoxifen maculopathy. However, the transition line disruption and the exact location and extent of cysts were not visible using time domain OCT in their study. Our case showed numerous hyperreflective deposits at the macula within the inner retinal layers mainly in the nerve fiber layer and plexiform layers that supported the Kupfer et al suggestion of formation of crystalline deposits as a result of axonal degeneration.8 In our case, the external limiting membrane, the Inner Segment-Outer Segment junction, and the photoreceptor layer were not discernable at the fovea in the SDOCT. As pointed out by Chung et al,2 these outer retinal details might have been missed by the time domain OCT. In the left eye, in addition to many hyperreflective deposits at the macula, there was loss of photoreceptors probably because of the toxic effects of the degenerative deposits. Our case also had few cystoid spaces at the macula as reported by others. The occurrence of large retinal spike-like deposit at the fovea projecting into the vitreous seen in our case was not described earlier. This may be because of the higher cumulative dose of tamoxifen. There is a report of foveal hyperfluorescence in tamoxifen retinopathy by Kim and colleagues. Our patient had macular and foveolar hypofluorescence in addition to foveal hyperfluorescence. To the best of our knowledge, this is the first report of macular and foveolar hypofluorescence in a case of tamoxifen retinopathy. With the available
literature, it is recommended that the SD-OCT and autofluorescence screening should be done in patients on tamoxifen with no specific visual complaints or in patients with visual complaints but with no specific abnormalities upon routine eye testing. The clear delineation of intraretinal layers by SD-OCT will surely improve our understanding of the pathogenesis of tamoxifen retinopathy. Key words: fundus autofluorescence, optical coherence tomography, tamoxifen retinopathy. References 1. Srikantia N, Mukesh S, Krishnaswamy M. Crystalline maculopathy: a rare complication of tamoxifen therapy. J Can Res Ther 2010;6:313–315. 2. Chung H, Kim D, Ahn SH, et al. Early detection of tamoxifen-induced maculopathy in patients with low cumulative doses of tamoxifen. Ophthalmic Surg Lasers Imaging 2010;41:e1–e5. 3. Drenser K, Sarraf D, Jain A, et al. Crystalline retinopathies. Surv Ophthalmol 2006;51:535–549. 4. Yanyali AC, Freund KB, et al. Tamoxifen retinopathy in a male patient. Am J Ophthalmol 2001;131:386–387. 5. Gualino V, Cohen SY, et al. Optical coherence tomography findings in tamoxifen retinopathy. Am J Ophthalmol 2005;140:757–758. 6. Gianni L, Panzini I, Li S, et al. Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer. Cancer 2006;106:505–513. 7. Bourla DH, Sarraf D, et al. Peripheral retinopathy and maculopathy in high-dose tamoxifen therapy. Am J Ophthalmol 2007;144:126–128. 8. Kaiser-Kupfer M.I., Kupfer C, Rodrigues M.M. Tamoxifen Retinopathy-A clinicopathologic report. Ophthalmology 1981; 88:89–93.
Purpose: To report spectral domain optical coherence tomography findings in a case of typical tamoxifen retinopathy. Methods: In this observational case report, a patient with tamoxifen retinopathy was imaged with spectral domain optical coherence tomography and fundus auto fluorescence. Results: Spectral domain optical coherence tomography showed numerous hyperreflective spots within the retina, mainly in the inner retinal layers in both the eyes. The external limiting membrane, the Inner Segment-Outer Segment junction, and the photoreceptors were not discernable at the fovea in the right eye. In the left eye, there was foveal atrophy with total loss of photoreceptors. The autofluorescent images showed macular hypofluorescence with foveal hyperfluorescence. Conclusion: Spectral domain optical coherence tomography demonstrated abnormalities in the outer retinal layers in tamoxifen retinopathy. There were also characteristic alterations in the autofluorescence pattern at the macula in tamoxifen retinopathy. RETINAL CASES & BRIEF REPORTS 7:128–130, 2013
SD-OCT showed numerous hyperreflective deposits at the macula mainly within the inner retinal layers (up to the outer plexiform layer). There was a large hyperreflective spike at the center of the fovea projecting into the vitreous. There was also foveal thinning in the right eye (macular thickness was 175 mm). The external limiting membrane, Inner Segment-Outer Segment junction, and the photoreceptors were not discernable at the fovea in the scan. There was mild macular edema nasal to the fovea in the right eye (Figure 2). In the left eye also there were many hyperreflective deposits at the macula in the inner retinal layers. Large deposits at the fovea slightly projecting into the vitreous were found. There was foveal atrophy in the left eye with total loss of photoreceptors (macular thickness was 170 mm in the left eye). Few cystoid spaces at the macula nasal to the fovea in the left eye were also found (Figure 3). Autofluorescent pictures of both eyes showed generalized reduction of autofluorescence at macula with increased autofluorescence at the fovea. The decreased fluorescence at the macula may be due to the absorption of fluorescent energy by the deposits and the increased fluorescence at the fovea may be because of the unmasking of retinal pigment epithelium lipofuschin secondary to foveal thinning. The foveolar spike in the right eye was hypofluorescent (Figure 4).
From the Giridhar Eye Institute, Kadavanthra, India. Case Report A 43-year-old woman presented with progressive worsening of vision in both eyes. In 2003, she was diagnosed with locally invasive pelvic fibromatosis. She underwent wide excision surgery twice, first in February 2003 and then in November of the same year. Postoperatively, she was given 20 mg per day of tamoxifen. However, the tumor recurred 5 months later, and it was deemed inoperable. She was given 23 cycles of radiotherapy and her tamoxifen dosage was increased to 200 mg per day. She received a cumulative dose of 500 g of tamoxifen, which was quite high. In February 2011, she presented to us with a 3-month history of progressive dimness of vision in both eyes. On examination, her Snellen visual acuity was 6/18 N8 in both eyes, and she had normal anterior segment and intraocular pressure. Dilated fundus examination showed numerous refractile crystals at the macula in both the eyes almost symmetrically (Figure 1). Spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence were performed in both eyes using Spectralis (Heidelberg Engineering, Heidelberg, Germany). In the right eye,
Discussion
The authors have no financial or conflicts of interest to disclose. Reprint requests: Sandhya Narayanan Nair, MS, Ponneth Temple Road, Kadavanthra, Cochin 682020, India; e-mail: [email protected]
Tamoxifen is an anti-estrogen drug used most commonly in the management of hormone receptor–positive 128
SD-OCT IN TAMOXIFEN RETINOPATHY
129
Fig. 1. Colour fundus photographs with tamoxifen retinopathy showing refractile deposits at macula.
breast cancer. However, in our case, this was given for a recurrent locally invasive pelvic fibromatosis. Ocular complications are rare and occur in 0.6% of patients and include cataract, vortex keratopathy, optic neuritis, and retinopathy.1 In the literature, patients with tamoxifen retinopathy had a cumulative dose ranging from 6 to 81 g. However, more recent reports demonstrate maculopathies occurring at much lower cumulative doses (4.2–9.6 g).2 Up to 12% of patients taking 20 mg per day of tamoxifen develop retinal toxicity.3 The huge foveal deposit seen in this case is most probably because of the high cumulative dose of tamoxifen. There are also reports of tamoxifen retinopathy in male patients who were given tamoxifen for inoperable hepatocellular carcinoma.4 The pathogenesis
Fig. 2. Spectral domain optical coherence tomography of the right eye showing inner retinal deposits, foveal thinning, and the spike-like deposit at the fovea. The Inner Segment-Outer Segment junction could not be seen clearly.
Fig. 3. Spectral domain optical coherence tomography of the left eye showing cystoid spaces.
is thought to be increased accumulation of glutamate that leads to axonal degeneration (observed histopathologically). The crystals seen on fundus examination correspond to the degenerative products.5 Extensive deposits may result in macular edema and impaired visual acuity. Visual acuity may improve with the withdrawal of tamoxifen along with resolution of macular edema, but retinal deposits often do not regress.6 Gualino et al5 reported OCT findings in two cases of tamoxifen retinopathy, which showed foveal cystoid space, with interruption of the photoreceptor layer without increase in macular thickness that indicated atrophy of the retinal tissue in the fovea. Bourla et al7 showed macular cystoid spaces associated with fluorescein leakage in one patient and fluorescein leakage without cystoid space in another patient. Both patients
Fig. 4. Autofluorescent images of right and left eyes with tamoxifen retinopathy showing macular hypofluorescence and foveal hyperfluorescence. The foveal spike in the right eye was hypofluorescent.
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showed hyperreflective deposits in the inner retinal layers at the macula and periphery.7 Chung et al2 observed intraretinal cysts and focal disruptions of the photoreceptor transition lines on three-dimensional OCT of patients with tamoxifen maculopathy. However, the transition line disruption and the exact location and extent of cysts were not visible using time domain OCT in their study. Our case showed numerous hyperreflective deposits at the macula within the inner retinal layers mainly in the nerve fiber layer and plexiform layers that supported the Kupfer et al suggestion of formation of crystalline deposits as a result of axonal degeneration.8 In our case, the external limiting membrane, the Inner Segment-Outer Segment junction, and the photoreceptor layer were not discernable at the fovea in the SDOCT. As pointed out by Chung et al,2 these outer retinal details might have been missed by the time domain OCT. In the left eye, in addition to many hyperreflective deposits at the macula, there was loss of photoreceptors probably because of the toxic effects of the degenerative deposits. Our case also had few cystoid spaces at the macula as reported by others. The occurrence of large retinal spike-like deposit at the fovea projecting into the vitreous seen in our case was not described earlier. This may be because of the higher cumulative dose of tamoxifen. There is a report of foveal hyperfluorescence in tamoxifen retinopathy by Kim and colleagues. Our patient had macular and foveolar hypofluorescence in addition to foveal hyperfluorescence. To the best of our knowledge, this is the first report of macular and foveolar hypofluorescence in a case of tamoxifen retinopathy. With the available
literature, it is recommended that the SD-OCT and autofluorescence screening should be done in patients on tamoxifen with no specific visual complaints or in patients with visual complaints but with no specific abnormalities upon routine eye testing. The clear delineation of intraretinal layers by SD-OCT will surely improve our understanding of the pathogenesis of tamoxifen retinopathy. Key words: fundus autofluorescence, optical coherence tomography, tamoxifen retinopathy. References 1. Srikantia N, Mukesh S, Krishnaswamy M. Crystalline maculopathy: a rare complication of tamoxifen therapy. J Can Res Ther 2010;6:313–315. 2. Chung H, Kim D, Ahn SH, et al. Early detection of tamoxifen-induced maculopathy in patients with low cumulative doses of tamoxifen. Ophthalmic Surg Lasers Imaging 2010;41:e1–e5. 3. Drenser K, Sarraf D, Jain A, et al. Crystalline retinopathies. Surv Ophthalmol 2006;51:535–549. 4. Yanyali AC, Freund KB, et al. Tamoxifen retinopathy in a male patient. Am J Ophthalmol 2001;131:386–387. 5. Gualino V, Cohen SY, et al. Optical coherence tomography findings in tamoxifen retinopathy. Am J Ophthalmol 2005;140:757–758. 6. Gianni L, Panzini I, Li S, et al. Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer. Cancer 2006;106:505–513. 7. Bourla DH, Sarraf D, et al. Peripheral retinopathy and maculopathy in high-dose tamoxifen therapy. Am J Ophthalmol 2007;144:126–128. 8. Kaiser-Kupfer M.I., Kupfer C, Rodrigues M.M. Tamoxifen Retinopathy-A clinicopathologic report. Ophthalmology 1981; 88:89–93.
