- Email: [email protected]
The optical imaging and clinical features of tamoxifen associated macular hole: A case report and review of the literatures
Accepted Manuscript Title: The Optical Imaging and Clinical Features of Tamoxifen Associated Macular Hole: A Case Report and Review of the Literatures Author: Yuedong Hu PhD Liu Ningning Yanyan Chen PhD PII: DOI: Reference:
S1572-1000(16)30213-7 http://dx.doi.org/doi:10.1016/j.pdpdt.2016.10.004 PDPDT 840
To appear in:
Photodiagnosis and Photodynamic Therapy
Received date: Revised date: Accepted date:
13-1-2016 27-9-2016 12-10-2016
Please cite this article as: Hu Yuedong, Ningning Liu, Chen Yanyan.The Optical Imaging and Clinical Features of Tamoxifen Associated Macular Hole: A Case Report and Review of the Literatures.Photodiagnosis and Photodynamic Therapy http://dx.doi.org/10.1016/j.pdpdt.2016.10.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The Optical Imaging and Clinical Features of Tamoxifen Associated Macular Hole: A Case Report and Review of the Literatures Yuedong Hu PhD1, 2, Liu Ningning1, 2, Yanyan Chen PhD3, 4
1.
Department of Ophthalmology, the First Affiliated Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang City, Liaoning Province, 110001, the People’s Republic of China
2.
Diabetic Eye Center of Liaoning province. No. 155 Nanjing Bei Street, Heping District, Shenyang City, Liaoning Province, 110001, the People’s Republic of China
3.
Department of Geriatrics, The First Affiliated Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang City, Liaoning Province, 110001, the People’s Republic of China
4.
The Key Laboratory of Endocrine diseases in Liaoning Province, The First Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang City, Shenyang, PR China, 110001.
Corresponding author: Yanyan Chen Phone: (+86)24-83283765 Fax: (+86) 24-83283294 E-mail: [email protected]
Disclosure Statement: The author have nothing to disclose.
Highlights
Macular hole is a rare complication of low-dosage-tamoxifen treatment as adjuvant treatment for breast carcinoma.
We described the typical optical imaging and clinical features of tamoxifen associated macular hole.
Tamoxifen is widely used in clinic, the pathological and treatment of tamoxifen associated macular hole should be further investigated.
Abstract We report a case of tamoxifen associated macular hole with typical optical imaging and clinical features. A 53-year-old woman came to our department for gradual decrees of vision acuity in both eyes for 3 months after 30 months low-dosage-tamoxifen treatment as adjuvant treatment for invasive ductal breast carcinoma. Her best corrected visual acuity (BCVA) was 0.4 in the right eye and 0.12 in the left eye. Dilated fundus examination showed macular multiple, fine, crystalline deposits and small white points in retina of both eyes. Blue light fundus autofluorescence showed fovea local hyper-fluorescence. Fluorescein angiography showed fovea local hyper-fluorescence in early stage and stain in late stage. Optical coherence tomography were performed. There were many point hyper-reflections in posterior retina in both eyes with fovea local posterior vitreous body detachment. Inner fovea mismatching, intact outer limiting membrane, bluer interdigitation zone, ruptured Ellipsoid zone and granular change of outer segments of photoreceptors were found in right eye. Blured interdigitation zone and granular change of outer segments of photoreceptors were also found in left eye with macular hole. Multifocal electroretinogram revealed reduced response in paracentral and pericentral area in both the eyes. And we reviewed the diagnosis and treatment of the disease.
Key words: tamoxifen; macular hole; blue light fundus autofluorescence; fluorescein angiography; optical coherence tomography; multifocal electroretinogram
Introduction Tamoxifen is an oral nonsteroidal selective estrogen receptor modulator, which is used for the adjuvant treatment of patients with hormone receptor positive breast cancer. 1 Tamoxifen has proven to be well-tolerated relatively free of serious side-effects, but some ocular complications such as retinopathy, keratopathy, cataract, and optic neuritis are reported.2, 3 Retinopathy is the most frequently reported ocular toxicity of tamoxifen. Crystalline deposition in the inner layer of retina, cystoid macular edema, branch retinal vein occlusion (BRVO)4 and macular holes (MH) associated with tamoxifen have been reported.5-11 Herein, we report a case of MH or its precursor secondary to tamoxifen therapy in a Chinese woman.
Case A 53-year-old premenopausal Chinese woman, diagnose as estrogen receptor (ER) (+) breast invasive ductal carcinoma in left side and accepted a radical mastectomy 3 years ago. After finished four cycles of post-operative chemotherapy (5-Fluorouracil 500mg/m2, doxorubicin 50mg/m2, and cyclophosphamide 500mg/m2), She was given tamoxifen 20mg daily as adjuvant treatment for 30 months. She came to our department for gradual decrees of vision acuity in both eyes for 3 months. On ophthalmological examination, her best corrected visual acuity (BCVA) was 0.4 in the right eye and 0.12 in the left eye. Papillary evaluation, intraocular pressure and anterior segment were normal. Dilated fundus examination showed macular multiple, fine, crystalline deposits and small white points in retina of both eyes [Figure1a,c]. Blue light fundus autofluorescence (BLFAF) showed fovea local hyper-fluorescence [Figure1b,d]. Fluorescein angiography (FA) showed fovea local hyper-fluorescence in early stage and stain in late stage [Figure1e,f,g,h]. Optical coherence tomography (OCT) (Spectralis OCT; Heidelberg Engineering; Heidelberg; Germany) radial scan and transverse
scan
were
performed
[Figure1g,j].
There
were
many
point
hyper-reflections in posterior retina in both eyes with fovea local posterior vitreous
body detachment. Inner fovea mismatching, intact outer limiting membrane, bluer interdigitation zone, ruptured Ellipsoid zone and granular change of outer segments of photoreceptors were found in right eye. Blured interdigitation zone and granular change of outer segments of photoreceptors were also found in left eye with macular hole. Multifocal electroretinogram (mf-ERG) (ROLAND system) revealed reduced response in paracentral and pericentral area in both the eyes [Figure1h,k]. With tamoxifen history for nearly 3 years, crystalline maculopathy secondary to tamoxifen therapy was diagnosed. Tamoxifen therapy was discontinued and been followed up for 3 months. In the last follow-up, visual acuity was not improved and OCT revealed no changes noted in the right and enlarged macular hole in the left eye.
Discussion The structure of tamoxifen is similar to other cationic amphiphilic drugs, such as chlorpromazine, thioridazine, chloroquine,and amiodarone hydrochloride, which are known to produce retinopathy and keratopathy. Crystalline retinopathy and cystoid macular edema (CME) are the typical tamoxifen ocular side-effects in high-dose tamoxifen treated patients with daily dosage excessing 120 mg daily6. Clinically significant ocular toxicity was seldom reported since the daily standard dose of tamoxifen was reduced to 20 mg. The ocular side-effects such as keratopathy12, cataract13, impaired visual acuity, ocular irritation and optical neuritis14，have been reported several clinical trials.2,3,2,
13-15
Other retinal alterations such as peripheral
crystalline retinopathy6 and branch retinal vein occlusion4 are rarely reported in cases reports. In recent years, several cases similar with our case of tamoxifen associated maculopathy were demonstrated in literatures. They have similar characteristics but named differently such as “crystalline deposition associated with mild macular edema”16, “foveolar cystoid space”17，“crystalline maculopathy” 8, 18, 11
“macular hole” 10,
, “tamoxifen maculopathy” 5 and “pseudocystic foveal cavitation” 7.They are conmen
in fundus manifestations as perifoveal multiple, fine, crystalline deposits. FA showed fovea local hyper-fluorescence in early stage and stain without leakage in late stage. Mf-ERG show reduced responses in pericentral and paracentral areas without
specificity8 . The OCT features vary from draping of the internal limiting membrane over a small cavitary space in the central fovea
5,7
, foveal cystic changes with outer
retinal defect10 to macular hole10 with a few hyper-relective dot-like echoes were seen intraretinally at the fovea, which might be different stages of macular hole. Cronin, B. G et al. retrospective analyzed the medical and surgical histories of 300 consecutive cases of macular hole surgery by a single surgeon between 1999 and 2003. The study demonstrates a strong link between tamoxifen use and macular holes.11 ER is expressed in the retina.19 E2 could attenuate the release of cytokines and reactive oxygen species microglial cells.20 ER agonists can protect retinal pigmental epithelium (RPE) against cytotoxic effects of oxysterols derived by enzymatic reactions. Increased oxysterols levels can decrease ER.21 Tamoxifen might act as an antagonist of glutamate transporters in RPE cells which led to an increase in glutamate and inducing axonal degeneration of Müller cell.22 Müller cell impairment may lead to retinal neuron injury and formation of intraretinal foveolar cyst.17, 23 Eisner, A. et al. proved with OCT that the foveas of women using anastrozole appeared to be subjected to more tractional force than the foveas of women not using any hormonal medication.24 This traction is oriented perpendicularly to the retinal surface which appear to initiate the hole. Tamoxifen should be discontinued or not is still a question. Prolonged tamoxifen durations (5 vs 2 years) conferred further survival benefits in breast cancer patients. 25 Moreover, if discontinued, how great the survival rate will be affected and how much the MH could be recovered? Chung, S. E. reported several cases of tamoxifen associated MH achieved visual improvement through surgery.
Tamoxifen is widely
used in clinic, the pathological and treatment of tamoxifen associated MH should be further investigated.
References: 1.
Hind D, Wyld L, Reed MW. Surgery, with or without tamoxifen, vs tamoxifen alone for
older women with operable breast cancer: cochrane review. British journal of cancer 2007;
96(7): 1025-9. 2.
Pemmaraju N, Munsell MF, Hortobagyi GN, Giordano SH. Retrospective review of male
breast cancer patients: analysis of tamoxifen-related side-effects. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 2012; 23(6): 1471-4. 3.
Dulley P. Ocular adverse reactions to tamoxifen--a review. Ophthalmic & physiological
optics : the journal of the British College of Ophthalmic Opticians (Optometrists) 1999; 19 Suppl 1: S2-9. 4.
Onder HI, Kilic AC, Kose SA, et al. Branch retinal vein occlusion associated with
tamoxifen use. Seminars in ophthalmology 2013; 28(2): 88-90. 5.
Akshay Gopinathan Nair, Debmalya Das, Anshul Goyal, Gandhi RA. The Eyes Have It!
Tamoxifen
Maculopathy
Revisited:
A
Case
Report.
JOURNAL
OF
OCULAR
PHARMACOLOGY AND THERAPEUTICS 2012; 28(6): 3. 6.
Bourla DH, Sarraf D, Schwartz SD. Peripheral retinopathy and maculopathy in high-dose
tamoxifen therapy. American journal of ophthalmology 2007; 144(1): 126-8. 7.
Doshi RR, Fortun JA, Kim BT, Dubovy SR, Rosenfeld PJ. Pseudocystic foveal cavitation
in tamoxifen retinopathy. American journal of ophthalmology 2014; 157(6): 1291-8 e3. 8.
Srikantia N, Mukesh S, Krishnaswamy M. Crystalline maculopathy: a rare complication of
tamoxifen therapy. Journal of cancer research and therapeutics 2010; 6(3): 313-5. 9.
J.R. EVANS, S.D. SCHWARTZ, J.D.A McHUGH, et al. Systemic risk factors for idiopathic
macular holes a case-control study. Eye 1998; 12: 4. 10. Chung SE, Kim SW, Chung HW, Kang SW. Estrogen antagonist and development of macular hole. Korean journal of ophthalmology : KJO 2010; 24(5): 306-9. 11. Cronin BG, Lekich CK, Bourke RD. Tamoxifen therapy conveys increased risk of developing a macular hole. International ophthalmology 2005; 26(3): 101-5. 12. Tarafdar S, Lim LT, Collins CE, Ramaesh K. Tamoxifen keratopathy as seen with in-vivo confocal microscopy. Seminars in ophthalmology 2012; 27(1-2): 27-8. 13. Paganini-Hill. A, Clark. LJ. Eye problems in breast cancer patiens treated with tamoxifen. Breast cancer research and treatment 2000; 60: 5. 14. Gianni L, Panzini I, Li S, et al. Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer: results from International Breast Cancer Study Group trials. Cancer 2006; 106(3): 505-13. 15. Noureddin. Bn, Seoud. M, Bashshur. Z, Salem. Z, Shamseddin. A, Khalil. A. Ocular toxicity in low -dose tamoxifen: a prospective study. Eye 1999; 13: 4. 16. David Sarraf MER, MD; Amani A. Fawzi, MD; Elliott Sohn, MD; Irene Barbazetto, MD;, David N. Zacks M, PhD; Robert A. Mittra, MD; JamesM. Klancnik Jr, MD; Sarah Mrejen, MD;, Naomi R. Goldberg M, PhD; Robert Beardsley, MD; John A. Sorenson, MD; K. Bailey Freund,MD. Paracentral acute middle maculopathy A New Variant of Acute Macular Neuroretinopathy Associated With Retinal Capillary Ischemia. JAMA Ophthalmol 2013; 131(10): 13. 17. Gualino V, Cohen SY, Delyfer MN, Sahel JA, Gaudric A. Optical coherence tomography findings in tamoxifen retinopathy. American journal of ophthalmology 2005; 140(4): 757-8. 18. Ritter C, Renner AB, Wachtlin J, Bechrakis NE, Krause L. [Tamoxifen retinopathy: a case series of clinical and functional data]. Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft 2008; 105(6): 544-9.
19. Ogueta SB, Schwartz SD, Yamashita CK, Farber DB. Estrogen receptor in the human eye: influence of gender and age on gene expression. Investigative ophthalmology & visual science 1999; 40(9): 1906-11. 20. Habib P, Beyer C. Regulation of brain microglia by female gonadal steroids. The Journal of steroid biochemistry and molecular biology 2015; 146: 3-14. 21. Dasari B, Prasanthi JR, Meiers C, Singh BB, Ghribi O. Differential effects of the estrogen receptor agonist estradiol on toxicity induced by enzymatically-derived or autoxidation-derived oxysterols in human ARPE-19 cells. Current eye research 2013; 38(11): 1159-71. 22. Kaiser-Kupfer MI, Kupfer C, Rodrigues MM. Tamoxifen retinopathy. A clinicopathologic report. Ophthalmology 1981; 88(1): 89-93. 23. Dyer MA, Cepko CL. Control of Muller glial cell proliferation and activation following retinal injury. Nature neuroscience 2000; 3(9): 873-80. 24. Eisner A, Thielman EJ, Falardeau J, Vetto JT. Vitreo-retinal traction and anastrozole use. Breast cancer research and treatment 2009; 117(1): 9-16. 25. Randomized trial of two versus five years of adjuvant tamoxifen for postmenopausal early stage breast cancer. Swedish Breast Cancer Cooperative Group. Journal of the National Cancer Institute 1996; 88(21): 1543-9.
Fig.1 Clinical features of tamoxifen associated macular hole. a,c: Fundus examination showed dark macular with multiple, fine, crystalline deposits in both eyes. b,d: Blue light fundus autofluorescence showed fovea local hyper-fluorescence e,f,g,h: Fluorescein angiography showed fovea local hyper-fluorescence in early stage and stain in late stage g,j: Optical coherence tomography. There were many point hyper-reflections in posterior retina in both eyes with fovea local posterior vitreous body detachment. Inner fovea mismatching, intact outer limiting membrane, bluer interdigitation zone, ruptured Ellipsoid zone and granular change of outer segments of photoreceptors were found in right eye. Blured interdigitation zone and granular change of outer segments of photoreceptors were also found in left eye with macular hole. h,k: Multifocal electroretinogram (mf-ERG) (ROLAND system) revealed reduced response in paracentral and pericentral area in both the eyes.
S1572-1000(16)30213-7 http://dx.doi.org/doi:10.1016/j.pdpdt.2016.10.004 PDPDT 840
To appear in:
Photodiagnosis and Photodynamic Therapy
Received date: Revised date: Accepted date:
13-1-2016 27-9-2016 12-10-2016
Please cite this article as: Hu Yuedong, Ningning Liu, Chen Yanyan.The Optical Imaging and Clinical Features of Tamoxifen Associated Macular Hole: A Case Report and Review of the Literatures.Photodiagnosis and Photodynamic Therapy http://dx.doi.org/10.1016/j.pdpdt.2016.10.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The Optical Imaging and Clinical Features of Tamoxifen Associated Macular Hole: A Case Report and Review of the Literatures Yuedong Hu PhD1, 2, Liu Ningning1, 2, Yanyan Chen PhD3, 4
1.
Department of Ophthalmology, the First Affiliated Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang City, Liaoning Province, 110001, the People’s Republic of China
2.
Diabetic Eye Center of Liaoning province. No. 155 Nanjing Bei Street, Heping District, Shenyang City, Liaoning Province, 110001, the People’s Republic of China
3.
Department of Geriatrics, The First Affiliated Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang City, Liaoning Province, 110001, the People’s Republic of China
4.
The Key Laboratory of Endocrine diseases in Liaoning Province, The First Hospital of China Medical University, No. 155 Nanjing Bei Street, Heping District, Shenyang City, Shenyang, PR China, 110001.
Corresponding author: Yanyan Chen Phone: (+86)24-83283765 Fax: (+86) 24-83283294 E-mail: [email protected]
Disclosure Statement: The author have nothing to disclose.
Highlights
Macular hole is a rare complication of low-dosage-tamoxifen treatment as adjuvant treatment for breast carcinoma.
We described the typical optical imaging and clinical features of tamoxifen associated macular hole.
Tamoxifen is widely used in clinic, the pathological and treatment of tamoxifen associated macular hole should be further investigated.
Abstract We report a case of tamoxifen associated macular hole with typical optical imaging and clinical features. A 53-year-old woman came to our department for gradual decrees of vision acuity in both eyes for 3 months after 30 months low-dosage-tamoxifen treatment as adjuvant treatment for invasive ductal breast carcinoma. Her best corrected visual acuity (BCVA) was 0.4 in the right eye and 0.12 in the left eye. Dilated fundus examination showed macular multiple, fine, crystalline deposits and small white points in retina of both eyes. Blue light fundus autofluorescence showed fovea local hyper-fluorescence. Fluorescein angiography showed fovea local hyper-fluorescence in early stage and stain in late stage. Optical coherence tomography were performed. There were many point hyper-reflections in posterior retina in both eyes with fovea local posterior vitreous body detachment. Inner fovea mismatching, intact outer limiting membrane, bluer interdigitation zone, ruptured Ellipsoid zone and granular change of outer segments of photoreceptors were found in right eye. Blured interdigitation zone and granular change of outer segments of photoreceptors were also found in left eye with macular hole. Multifocal electroretinogram revealed reduced response in paracentral and pericentral area in both the eyes. And we reviewed the diagnosis and treatment of the disease.
Key words: tamoxifen; macular hole; blue light fundus autofluorescence; fluorescein angiography; optical coherence tomography; multifocal electroretinogram
Introduction Tamoxifen is an oral nonsteroidal selective estrogen receptor modulator, which is used for the adjuvant treatment of patients with hormone receptor positive breast cancer. 1 Tamoxifen has proven to be well-tolerated relatively free of serious side-effects, but some ocular complications such as retinopathy, keratopathy, cataract, and optic neuritis are reported.2, 3 Retinopathy is the most frequently reported ocular toxicity of tamoxifen. Crystalline deposition in the inner layer of retina, cystoid macular edema, branch retinal vein occlusion (BRVO)4 and macular holes (MH) associated with tamoxifen have been reported.5-11 Herein, we report a case of MH or its precursor secondary to tamoxifen therapy in a Chinese woman.
Case A 53-year-old premenopausal Chinese woman, diagnose as estrogen receptor (ER) (+) breast invasive ductal carcinoma in left side and accepted a radical mastectomy 3 years ago. After finished four cycles of post-operative chemotherapy (5-Fluorouracil 500mg/m2, doxorubicin 50mg/m2, and cyclophosphamide 500mg/m2), She was given tamoxifen 20mg daily as adjuvant treatment for 30 months. She came to our department for gradual decrees of vision acuity in both eyes for 3 months. On ophthalmological examination, her best corrected visual acuity (BCVA) was 0.4 in the right eye and 0.12 in the left eye. Papillary evaluation, intraocular pressure and anterior segment were normal. Dilated fundus examination showed macular multiple, fine, crystalline deposits and small white points in retina of both eyes [Figure1a,c]. Blue light fundus autofluorescence (BLFAF) showed fovea local hyper-fluorescence [Figure1b,d]. Fluorescein angiography (FA) showed fovea local hyper-fluorescence in early stage and stain in late stage [Figure1e,f,g,h]. Optical coherence tomography (OCT) (Spectralis OCT; Heidelberg Engineering; Heidelberg; Germany) radial scan and transverse
scan
were
performed
[Figure1g,j].
There
were
many
point
hyper-reflections in posterior retina in both eyes with fovea local posterior vitreous
body detachment. Inner fovea mismatching, intact outer limiting membrane, bluer interdigitation zone, ruptured Ellipsoid zone and granular change of outer segments of photoreceptors were found in right eye. Blured interdigitation zone and granular change of outer segments of photoreceptors were also found in left eye with macular hole. Multifocal electroretinogram (mf-ERG) (ROLAND system) revealed reduced response in paracentral and pericentral area in both the eyes [Figure1h,k]. With tamoxifen history for nearly 3 years, crystalline maculopathy secondary to tamoxifen therapy was diagnosed. Tamoxifen therapy was discontinued and been followed up for 3 months. In the last follow-up, visual acuity was not improved and OCT revealed no changes noted in the right and enlarged macular hole in the left eye.
Discussion The structure of tamoxifen is similar to other cationic amphiphilic drugs, such as chlorpromazine, thioridazine, chloroquine,and amiodarone hydrochloride, which are known to produce retinopathy and keratopathy. Crystalline retinopathy and cystoid macular edema (CME) are the typical tamoxifen ocular side-effects in high-dose tamoxifen treated patients with daily dosage excessing 120 mg daily6. Clinically significant ocular toxicity was seldom reported since the daily standard dose of tamoxifen was reduced to 20 mg. The ocular side-effects such as keratopathy12, cataract13, impaired visual acuity, ocular irritation and optical neuritis14，have been reported several clinical trials.2,3,2,
13-15
Other retinal alterations such as peripheral
crystalline retinopathy6 and branch retinal vein occlusion4 are rarely reported in cases reports. In recent years, several cases similar with our case of tamoxifen associated maculopathy were demonstrated in literatures. They have similar characteristics but named differently such as “crystalline deposition associated with mild macular edema”16, “foveolar cystoid space”17，“crystalline maculopathy” 8, 18, 11
“macular hole” 10,
, “tamoxifen maculopathy” 5 and “pseudocystic foveal cavitation” 7.They are conmen
in fundus manifestations as perifoveal multiple, fine, crystalline deposits. FA showed fovea local hyper-fluorescence in early stage and stain without leakage in late stage. Mf-ERG show reduced responses in pericentral and paracentral areas without
specificity8 . The OCT features vary from draping of the internal limiting membrane over a small cavitary space in the central fovea
5,7
, foveal cystic changes with outer
retinal defect10 to macular hole10 with a few hyper-relective dot-like echoes were seen intraretinally at the fovea, which might be different stages of macular hole. Cronin, B. G et al. retrospective analyzed the medical and surgical histories of 300 consecutive cases of macular hole surgery by a single surgeon between 1999 and 2003. The study demonstrates a strong link between tamoxifen use and macular holes.11 ER is expressed in the retina.19 E2 could attenuate the release of cytokines and reactive oxygen species microglial cells.20 ER agonists can protect retinal pigmental epithelium (RPE) against cytotoxic effects of oxysterols derived by enzymatic reactions. Increased oxysterols levels can decrease ER.21 Tamoxifen might act as an antagonist of glutamate transporters in RPE cells which led to an increase in glutamate and inducing axonal degeneration of Müller cell.22 Müller cell impairment may lead to retinal neuron injury and formation of intraretinal foveolar cyst.17, 23 Eisner, A. et al. proved with OCT that the foveas of women using anastrozole appeared to be subjected to more tractional force than the foveas of women not using any hormonal medication.24 This traction is oriented perpendicularly to the retinal surface which appear to initiate the hole. Tamoxifen should be discontinued or not is still a question. Prolonged tamoxifen durations (5 vs 2 years) conferred further survival benefits in breast cancer patients. 25 Moreover, if discontinued, how great the survival rate will be affected and how much the MH could be recovered? Chung, S. E. reported several cases of tamoxifen associated MH achieved visual improvement through surgery.
Tamoxifen is widely
used in clinic, the pathological and treatment of tamoxifen associated MH should be further investigated.
References: 1.
Hind D, Wyld L, Reed MW. Surgery, with or without tamoxifen, vs tamoxifen alone for
older women with operable breast cancer: cochrane review. British journal of cancer 2007;
96(7): 1025-9. 2.
Pemmaraju N, Munsell MF, Hortobagyi GN, Giordano SH. Retrospective review of male
breast cancer patients: analysis of tamoxifen-related side-effects. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 2012; 23(6): 1471-4. 3.
Dulley P. Ocular adverse reactions to tamoxifen--a review. Ophthalmic & physiological
optics : the journal of the British College of Ophthalmic Opticians (Optometrists) 1999; 19 Suppl 1: S2-9. 4.
Onder HI, Kilic AC, Kose SA, et al. Branch retinal vein occlusion associated with
tamoxifen use. Seminars in ophthalmology 2013; 28(2): 88-90. 5.
Akshay Gopinathan Nair, Debmalya Das, Anshul Goyal, Gandhi RA. The Eyes Have It!
Tamoxifen
Maculopathy
Revisited:
A
Case
Report.
JOURNAL
OF
OCULAR
PHARMACOLOGY AND THERAPEUTICS 2012; 28(6): 3. 6.
Bourla DH, Sarraf D, Schwartz SD. Peripheral retinopathy and maculopathy in high-dose
tamoxifen therapy. American journal of ophthalmology 2007; 144(1): 126-8. 7.
Doshi RR, Fortun JA, Kim BT, Dubovy SR, Rosenfeld PJ. Pseudocystic foveal cavitation
in tamoxifen retinopathy. American journal of ophthalmology 2014; 157(6): 1291-8 e3. 8.
Srikantia N, Mukesh S, Krishnaswamy M. Crystalline maculopathy: a rare complication of
tamoxifen therapy. Journal of cancer research and therapeutics 2010; 6(3): 313-5. 9.
J.R. EVANS, S.D. SCHWARTZ, J.D.A McHUGH, et al. Systemic risk factors for idiopathic
macular holes a case-control study. Eye 1998; 12: 4. 10. Chung SE, Kim SW, Chung HW, Kang SW. Estrogen antagonist and development of macular hole. Korean journal of ophthalmology : KJO 2010; 24(5): 306-9. 11. Cronin BG, Lekich CK, Bourke RD. Tamoxifen therapy conveys increased risk of developing a macular hole. International ophthalmology 2005; 26(3): 101-5. 12. Tarafdar S, Lim LT, Collins CE, Ramaesh K. Tamoxifen keratopathy as seen with in-vivo confocal microscopy. Seminars in ophthalmology 2012; 27(1-2): 27-8. 13. Paganini-Hill. A, Clark. LJ. Eye problems in breast cancer patiens treated with tamoxifen. Breast cancer research and treatment 2000; 60: 5. 14. Gianni L, Panzini I, Li S, et al. Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer: results from International Breast Cancer Study Group trials. Cancer 2006; 106(3): 505-13. 15. Noureddin. Bn, Seoud. M, Bashshur. Z, Salem. Z, Shamseddin. A, Khalil. A. Ocular toxicity in low -dose tamoxifen: a prospective study. Eye 1999; 13: 4. 16. David Sarraf MER, MD; Amani A. Fawzi, MD; Elliott Sohn, MD; Irene Barbazetto, MD;, David N. Zacks M, PhD; Robert A. Mittra, MD; JamesM. Klancnik Jr, MD; Sarah Mrejen, MD;, Naomi R. Goldberg M, PhD; Robert Beardsley, MD; John A. Sorenson, MD; K. Bailey Freund,MD. Paracentral acute middle maculopathy A New Variant of Acute Macular Neuroretinopathy Associated With Retinal Capillary Ischemia. JAMA Ophthalmol 2013; 131(10): 13. 17. Gualino V, Cohen SY, Delyfer MN, Sahel JA, Gaudric A. Optical coherence tomography findings in tamoxifen retinopathy. American journal of ophthalmology 2005; 140(4): 757-8. 18. Ritter C, Renner AB, Wachtlin J, Bechrakis NE, Krause L. [Tamoxifen retinopathy: a case series of clinical and functional data]. Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft 2008; 105(6): 544-9.
19. Ogueta SB, Schwartz SD, Yamashita CK, Farber DB. Estrogen receptor in the human eye: influence of gender and age on gene expression. Investigative ophthalmology & visual science 1999; 40(9): 1906-11. 20. Habib P, Beyer C. Regulation of brain microglia by female gonadal steroids. The Journal of steroid biochemistry and molecular biology 2015; 146: 3-14. 21. Dasari B, Prasanthi JR, Meiers C, Singh BB, Ghribi O. Differential effects of the estrogen receptor agonist estradiol on toxicity induced by enzymatically-derived or autoxidation-derived oxysterols in human ARPE-19 cells. Current eye research 2013; 38(11): 1159-71. 22. Kaiser-Kupfer MI, Kupfer C, Rodrigues MM. Tamoxifen retinopathy. A clinicopathologic report. Ophthalmology 1981; 88(1): 89-93. 23. Dyer MA, Cepko CL. Control of Muller glial cell proliferation and activation following retinal injury. Nature neuroscience 2000; 3(9): 873-80. 24. Eisner A, Thielman EJ, Falardeau J, Vetto JT. Vitreo-retinal traction and anastrozole use. Breast cancer research and treatment 2009; 117(1): 9-16. 25. Randomized trial of two versus five years of adjuvant tamoxifen for postmenopausal early stage breast cancer. Swedish Breast Cancer Cooperative Group. Journal of the National Cancer Institute 1996; 88(21): 1543-9.
Fig.1 Clinical features of tamoxifen associated macular hole. a,c: Fundus examination showed dark macular with multiple, fine, crystalline deposits in both eyes. b,d: Blue light fundus autofluorescence showed fovea local hyper-fluorescence e,f,g,h: Fluorescein angiography showed fovea local hyper-fluorescence in early stage and stain in late stage g,j: Optical coherence tomography. There were many point hyper-reflections in posterior retina in both eyes with fovea local posterior vitreous body detachment. Inner fovea mismatching, intact outer limiting membrane, bluer interdigitation zone, ruptured Ellipsoid zone and granular change of outer segments of photoreceptors were found in right eye. Blured interdigitation zone and granular change of outer segments of photoreceptors were also found in left eye with macular hole. h,k: Multifocal electroretinogram (mf-ERG) (ROLAND system) revealed reduced response in paracentral and pericentral area in both the eyes.