Pseudocystic Foveal Cavitation in Tamoxifen Retinopathy




Purpose


To present 3 cases of tamoxifen-induced foveal cavitation and review previous prospective and cross-sectional studies.


Design


Observational case series.


Methods


Retrospective analysis of patients presenting to a single institution with evidence of tamoxifen-induced maculopathy.


Results


Three patients presented with pseudocystic foveal cavitation similar in appearance to macular telangiectasia type 2 on spectral-domain optical coherence tomography (SD OCT) imaging.


Conclusions


Tamoxifen maculopathy is characterized by cavitation in the central macula with or without typical cystoid macular edema. Pathogenesis involves toxicity to retinal Müller cells. It can occur with low daily and cumulative doses of the drug, and in the absence of subjective visual complaints or crystalline retinopathy. Prospective research with SD OCT imaging will be required to gain a more accurate estimate of the incidence of tamoxifen retinopathy.


Tamoxifen is an oral anti-estrogen used for the treatment of metastatic breast cancer, as adjuvant endocrine therapy for breast cancer, for prevention of invasive breast cancer in patients with treated ductal carcinoma in situ, and for primary prevention of breast cancer in high-risk women. It has also been used in the treatment of other malignancies, notably malignant central nervous system gliomas; for ovulation induction in women with infertility; and as treatment for precocious puberty in patients with McCune-Albright syndrome. Systemic side effects include an increased risk of thromboembolic events and endometrial cancer. Ocular toxicity includes keratopathy, cataract, and optic neuritis, but has most commonly been described as a crystalline retinopathy with or without cystoid macular edema (CME). More recent studies using spectral-domain optical coherence tomography (SD OCT) imaging have documented the presence of cavitary spaces or pseudocysts in the central macula without typical CME.


Currently, a 5-year course of tamoxifen for adjuvant endocrine therapy of hormone receptor–positive breast cancer is the standard of care. A recent meta-analysis demonstrated significant additional reductions in the risks of death and relapse in patients treated with an extended course of tamoxifen beyond 5 years. The prolonged use of tamoxifen therapy in oncologic care may necessitate renewed surveillance by ophthalmologists for tamoxifen toxicity.


We present 3 cases of tamoxifen-induced cavitary spaces imaged with SD OCT and review previous prospective and cross-sectional studies estimating the incidence and prevalence of tamoxifen retinopathy.


Methods


This is an observational case series of 3 patients presenting to the Bascom Palmer Eye Institute. The University of Miami Institutional Review Board waived the need for approval based on the limited number of patients involved and the observational nature of the study. The study adhered to the tenets of the Declaration of Helsinki and was in accordance with HIPAA regulations and all federal and state laws.




Results


Case 1


A 63-year-old Haitian woman presented for a second opinion on macular edema. She had not noticed any problem with her vision until 1.5 years prior to presentation, when on routine examination her optometrist could not correct her vision with glasses and sent her to a retina specialist. She was diagnosed with bilateral macular edema and given a single injection of bevacizumab in the right eye. By history, a fluorescein angiogram (FA) was not obtained. She experienced no change in vision from the injection and never returned to her doctor for follow-up. She had no prior ocular history and did not seek additional care until presenting to our clinic.


Her medical history included hypertension, hypercholesterolemia, and stage 1 breast cancer treated with a left mastectomy 14 years prior. Current medications were amlodipine, valsartan, allopurinol, and atorvastatin. She had been placed on tamoxifen 20 mg daily for a total of 5 years following the mastectomy (cumulative dose, 36.5 g). Upon further questioning, she reported some difficulty reading but could not say when the symptom had developed.


Examination revealed a best-corrected visual acuity (BCVA) of 20/60 in the right eye and 20/50 in the left eye. Pupils and confrontation visual fields were normal. Slit-lamp examination demonstrated mild nuclear and cortical sclerotic cataracts in both eyes. On funduscopy, the foveal light reflex was irregular in both eyes, and yellow spots were present in both posterior poles, most prominently temporal to the fovea ( Figure 1 ). Autofluorescence (AF) imaging showed punctate hyperautofluorescent foci corresponding to the yellow spots seen clinically, as well as absence of the normal foveal hypoautofluorescence. On SD OCT, cavitary spaces with disruption of the outer retinal bands were present in both eyes, left greater than right. Point-to-point correlation between the AF and SD OCT images did not demonstrate an obvious SD OCT correlate for the hyperautofluorescent foci ( Figure 2 ). FA revealed mild hyperfluorescence in the central macula with no leakage.




Figure 1


Case 1: Pseudocystic foveal cavitation in tamoxifen retinopathy. (Top left) Color fundus photograph of the right eye demonstrates yellow spots in the posterior pole, (Top middle) corresponding to punctate hyperautofluorescent foci on autofluorescence imaging. There is an absence of normal hypoautofluorescence in the fovea. (Top right) Spectral-domain optical coherence tomography imaging demonstrates foveal cavitary spaces. (Bottom) Similar findings are present in the left eye, with more pronounced cavitation.



Figure 2


Case 1: Point-to-point correlation of punctate hyperautofluorescent foci with optical coherence tomography (OCT) scans (cropped to the area of interest) in tamoxifen retinopathy. (Top left) Fundus autofluorescence image with the spectral-domain (SD) OCT B-scan depicted as a horizontal line corresponding to the lesion. (Top right) SD OCT B-scan showing no obvious lesion analogue visible on SD OCT. (Bottom) Similar findings in the left eye.


Case 2


A 50-year-old woman presented with distortion in the left eye for 1 year. She had no prior ocular history. Past medical history was significant for breast cancer treated with lumpectomy and radiation 3 years prior to presentation, after which she was placed on tamoxifen 20 mg daily for 2.5 years (cumulative dose, 18.25 g). Her oncologist discontinued the medication after the patient developed visual symptoms and an ophthalmologist documented crystalline retinopathy.


Examination revealed a BCVA of 20/25 in the right eye and 20/30 in the left eye. Mild nuclear sclerotic cataracts were present in both eyes. Funduscopy demonstrated altered pigmentation of the fovea in both eyes, with fine crystals in the right eye ( Figures 3 and 4 ). AF imaging showed reduction of the normal foveal hypoautofluorescence in both eyes, left greater than right. Blue light reflectance (BLR) imaging revealed punctate bright lesions in the right fovea, corresponding to the crystals seen clinically. On SD OCT, thinning of the inner retina with draping of the internal limiting membrane was present in the right eye, and near-full-thickness cavitation was present in the left eye. FA revealed mild hyperfluorescence without leakage in the left eye greater than the right eye.




Figure 3


Case 2: Multimodal imaging of pseudocystic foveal cavitation in tamoxifen retinopathy, right eye. (Top left) Color fundus photograph of the right eye demonstrates fine juxtafoveal crystals and 2 additional yellow spots in the superotemporal and inferotemporal macula. (Top right) Autofluorescence shows an absence of normal foveal hypoautofluorescence, with punctate hyperautofluorescence corresponding with the yellow spots seen on the color fundus photograph; the juxtafoveal crystals are not well defined. (Middle left) Blue light reflectance image highlights the juxtafoveal crystals. (Middle right) Fluorescein angiogram in the late phase demonstrates mild hyperfluorescence without leakage in the parafoveal region. (Bottom) Spectral-domain optical coherence tomography demonstrates draping of the internal limiting membrane over a small cavitary space in the central fovea.



Figure 4


Case 2: Multimodal imaging of pseudocystic foveal cavitation in tamoxifen retinopathy, left eye. (Top left) Color fundus photograph of the left eye demonstrates a yellow spot in the central fovea without crystals. (Top right) Autofluorescence shows absence of normal foveal hypoautofluorescence. (Middle left) Blue light reflectance image shows superficial light reflexes; no crystals are demonstrated. (Middle right) Fluorescein angiogram in the late phase demonstrates mild hyperfluorescence without leakage in the central fovea and parafoveal region. (Bottom) Spectral-domain optical coherence tomography demonstrates a near-full-thickness cavitation in the central fovea.


Case 3


A 52-year-old woman presented with blurred vision and a central dark spot in her left eye for 1 year. She had a history of breast cancer treated with bilateral mastectomy with chemotherapy and radiation 8 years prior to presentation, and had since been on tamoxifen 20 mg daily (cumulative dose 58.4 g).


Examination revealed a BCVA of 20/25 in the right eye and 20/40 in the left eye. Slit-lamp examination was within normal limits in both eyes, and funduscopy demonstrated fine crystals in both foveas, with a pseudohole appearance in the left eye ( Figure 5 ). AF imaging showed absence of the normal foveal hypoautofluorescence in both eyes, more pronounced in the left eye. On SD OCT, a cavitary space was present in the left eye. FA revealed hyperfluorescence in the fovea of the left eye greater than the right eye and no leakage was detected.




Figure 5


Case 3: Pseudocystic foveal cavitation in tamoxifen retinopathy. (Top left) Color fundus and (Top middle) autofluorescence imaging of the right eye demonstrate mild hypopigmentation in the central fovea with an accompanying absence of central hypoautofluorescence. (Top right) The fovea is thin on spectral-domain optical coherence tomography (SD OCT). (Bottom left) Color fundus and (Bottom middle) autofluorescence images of the left eye show a pseudohole appearance with absence of foveal hypoautofluorescence and (Bottom right) a near-full-thickness cavitary space on SD OCT.


In follow-up, early CME with a mild increase in retinal thickness was noted in the left eye. The patient had no history of diabetes or other conditions associated with CME. In consultation with the patient’s oncologist, tamoxifen was discontinued. Following discontinuation, the CME initially increased, then resolved without additional intervention ( Figure 6 ).




Figure 6


Case 3: Serial optical coherence tomography scans of the left eye demonstrate the development of cystoid macular edema in tamoxifen retinopathy with spontaneous resolution following discontinuation of tamoxifen. (Top) Left eye of patient at first visit while on 20 mg daily tamoxifen with visual acuity (VA) of 20/50. The left image represents the scanning laser ophthalmoscopic image with the superimposed retinal thickness map and location of the horizontal and vertical B-scans through the fovea from the spectral-domain optical coherence tomography instrument. The right image depicts the horizontal B-scan through the fovea. (Upper middle) Six weeks later, a new cyst developed adjacent to the cavitary space, with a corresponding mild increase in retinal thickness; tamoxifen was discontinued the following day. (Lower middle) Six weeks after discontinuation of tamoxifen, cystoid macular edema (CME) increased; VA declined to 20/70. (Bottom) Eight weeks later, CME had resolved, but foveal cavitation persisted and VA did not improve.




Results


Case 1


A 63-year-old Haitian woman presented for a second opinion on macular edema. She had not noticed any problem with her vision until 1.5 years prior to presentation, when on routine examination her optometrist could not correct her vision with glasses and sent her to a retina specialist. She was diagnosed with bilateral macular edema and given a single injection of bevacizumab in the right eye. By history, a fluorescein angiogram (FA) was not obtained. She experienced no change in vision from the injection and never returned to her doctor for follow-up. She had no prior ocular history and did not seek additional care until presenting to our clinic.


Her medical history included hypertension, hypercholesterolemia, and stage 1 breast cancer treated with a left mastectomy 14 years prior. Current medications were amlodipine, valsartan, allopurinol, and atorvastatin. She had been placed on tamoxifen 20 mg daily for a total of 5 years following the mastectomy (cumulative dose, 36.5 g). Upon further questioning, she reported some difficulty reading but could not say when the symptom had developed.


Examination revealed a best-corrected visual acuity (BCVA) of 20/60 in the right eye and 20/50 in the left eye. Pupils and confrontation visual fields were normal. Slit-lamp examination demonstrated mild nuclear and cortical sclerotic cataracts in both eyes. On funduscopy, the foveal light reflex was irregular in both eyes, and yellow spots were present in both posterior poles, most prominently temporal to the fovea ( Figure 1 ). Autofluorescence (AF) imaging showed punctate hyperautofluorescent foci corresponding to the yellow spots seen clinically, as well as absence of the normal foveal hypoautofluorescence. On SD OCT, cavitary spaces with disruption of the outer retinal bands were present in both eyes, left greater than right. Point-to-point correlation between the AF and SD OCT images did not demonstrate an obvious SD OCT correlate for the hyperautofluorescent foci ( Figure 2 ). FA revealed mild hyperfluorescence in the central macula with no leakage.




Figure 1


Case 1: Pseudocystic foveal cavitation in tamoxifen retinopathy. (Top left) Color fundus photograph of the right eye demonstrates yellow spots in the posterior pole, (Top middle) corresponding to punctate hyperautofluorescent foci on autofluorescence imaging. There is an absence of normal hypoautofluorescence in the fovea. (Top right) Spectral-domain optical coherence tomography imaging demonstrates foveal cavitary spaces. (Bottom) Similar findings are present in the left eye, with more pronounced cavitation.



Figure 2


Case 1: Point-to-point correlation of punctate hyperautofluorescent foci with optical coherence tomography (OCT) scans (cropped to the area of interest) in tamoxifen retinopathy. (Top left) Fundus autofluorescence image with the spectral-domain (SD) OCT B-scan depicted as a horizontal line corresponding to the lesion. (Top right) SD OCT B-scan showing no obvious lesion analogue visible on SD OCT. (Bottom) Similar findings in the left eye.


Case 2


A 50-year-old woman presented with distortion in the left eye for 1 year. She had no prior ocular history. Past medical history was significant for breast cancer treated with lumpectomy and radiation 3 years prior to presentation, after which she was placed on tamoxifen 20 mg daily for 2.5 years (cumulative dose, 18.25 g). Her oncologist discontinued the medication after the patient developed visual symptoms and an ophthalmologist documented crystalline retinopathy.


Examination revealed a BCVA of 20/25 in the right eye and 20/30 in the left eye. Mild nuclear sclerotic cataracts were present in both eyes. Funduscopy demonstrated altered pigmentation of the fovea in both eyes, with fine crystals in the right eye ( Figures 3 and 4 ). AF imaging showed reduction of the normal foveal hypoautofluorescence in both eyes, left greater than right. Blue light reflectance (BLR) imaging revealed punctate bright lesions in the right fovea, corresponding to the crystals seen clinically. On SD OCT, thinning of the inner retina with draping of the internal limiting membrane was present in the right eye, and near-full-thickness cavitation was present in the left eye. FA revealed mild hyperfluorescence without leakage in the left eye greater than the right eye.


Jan 8, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Pseudocystic Foveal Cavitation in Tamoxifen Retinopathy
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