Diagnostic and Therapeutic Challenges
Edited by H. Richard McDonald
Drs. Gabriella De Salvo, Pearse A. Keane, Adnan Tufail, and David Sarraf
T
the small sub-RPE lesions. No evidence of vasculitis, disk leakage, or idiopathic polypoidal choroidal neovascularization was seen. B-scan ultrasonography demonstrated that total ocular coat thickness was within the normal range. Routine blood testing (including complete blood count, renal and liver function, serum angiotensin converting enzyme, and inflammatory markers) was unremarkable, as was a chest x-ray. Autoantibody testing and thyroid function was also within normal limits. In view of the unexplained hyperreflective areas distributed around the posterior pole, the patient was referred for further systemic investigations to exclude the possibility of a paraneoplastic syndrome. Clinical examinations of the chest, breast, abdomen, and lymph nodes were normal. Total body positron emission tomography (PET) and computed tomography scans were arranged and both came back normal with no evidence of malignancy. Six months after her initial presentation, her visual acuity was 6/12 in the right eye and 6/18 in the left eye. The subretinal and intraretinal fluid had resolved spontaneously, although the left eye showed an area of hyperreflectivity because of fibrosis. In the right eye, the sub-PED hyperreflective areas were now pushing the PED upward (Figure 2B). Eighteen months after her initial presentation, her best-corrected visual acuity was 6/9 in the right eye and 6/6 in the left eye. A repeat OCT again showed enlargement of bilateral PEDs and persistent multifocal hyperreflective areas under the RPE. These lesions were now migrating toward the outer nuclear layer causing disruption of the RPE, ellipsoid, and external limiting membrane (Figure 2C). Further investigations were performed, including dexamethasone suppression testing to exclude Cushing disease. These were all normal. The case is presented here for discussion of image interpretation and differential diagnosis.
his case is submitted by Dr. Gabriella De Salvo of Moorfields Eye Hospital NHS Foundation Trust, London, and University Hospital Southampton, Eye Unit, Southampton, United Kingdom; Dr. Pearse A. Keane of Moorfields Eye Hospital NHS Foundation Trust, and NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom, and UCL Institute of Ophthalmology, London, United Kingdom; and Dr. Adnan Tufail of Moorfields Eye Hospital NHS Foundation Trust; commented by Dr. David Sarraf, Los Angeles, California.
Case Report A 50-year-old Turkish woman presented to the Medical Retina Department of Moorfields Eye Hospital complaining of 2 months of bilateral blurred vision. She had a medical history of hypertension, treated with amlodipine and bendroflumethiazide, and hypercholesterolemia, treated with simvastatin. Both conditions were well controlled. On examination, her best-corrected visual acuity in the right eye was 3/60 and in her left eye was 6/24. Anterior segment examination was within normal limits. There were neither cells nor haze in the vitreous of either eye. Fundus examination showed bilateral pigment epithelial detachment (PED), multiple yellowish deep lesions at the posterior pole and in the nasal quadrants, and few retinal folds (Figure 1). Optical coherence tomography (OCT) showed bilateral large PEDs, with overlying subretinal fluid, and hyporeflective pseudocysts in the outer retinal layer. Within the PED and also outside the PED, but still underneath the retinal pigment epithelium (RPE), multiple small areas of hyperreflectivity were seen (Figure 2A). Fluorescein angiography and indocyanine green angiography were performed (Figure 3). The fluorescein angiography of the right eye showed pooling of the PED and multiple areas of staining at the level of the sub-RPE deposits, both beneath and around the PED. Indocyanine green angiography of the right eye showed a hypofluorescent area corresponding to the large PED and staining of the sub-RPE deposits. The left eye showed a similar pattern, but also with late “comma”-shaped leakage at the fovea. Indocyanine green angiography showed clearly a hyperfluorescent plaque and again staining of
Dr. David Sarraf (Los Angeles, California): De Salvo et al describe a very interesting case of a 50-year-old hypertensive Turkish woman who presents with significant bilateral vision loss. Spectral domain optical coherence tomography (SDOCT) demonstrates large PEDs with associated intraretinal and subretinal fluid in each eye. Fluorescein angiography confirms the presence of a very large serous PED with associated pooling central in the right eye and central leakage in a “comma”-shaped pattern in the left eye suggestive 374
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
375
Fig. 1. Fundus photograph showing bilateral PED and multiple yellowish deep deposits at the posterior pole and in the nasal quadrants.
of central serous retinopathy (CSR). In addition, there is multifocal staining of drusenoid deposits in each eye. The indocyanine angiogram demonstrates dilated
choroidal vessels in the right eye again suggestive of CSR, and also demonstrates staining of the drusenoid deposits in both eyes.
Fig. 2. Optical coherence tomography through the fovea (superior images) and superior to the fovea (inferior images). A. Bilateral PED with a hyporeflective area above the RPE and hyporeflective pseudocysts in the outer retinal layer. Hyporeflectivity anterior to the choriocapillaris with multiple small dots of hyperreflectivity, especially visualized in the inferior images. B. Resolved subretinal and intraretinal fluid. OD: SubPED hyperreflectivity spots are now “pushing” upward the PED. OS: Subretinal hyperreflectivity because of fibrosis, outer retinal tubulation, small residual PED in the inferior image. C. Bilateral PED and persistent multifocal hyperreflective dots under the RPE/PED migrating toward the outer nuclear layer with disruption of the RPE, ellipsoid, and external limiting membrane. OD, right eye; OS, left eye.
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RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES 2015 VOLUME 35 NUMBER 2
Fig. 3. Fluorescein angiography OD: Pooling of dye at the PED and staining at the level of the multiple sub-RPE deposits, both underneath and outside the PED. OS: Same as OD but late leakage from a hyperfluorescent foveal lesion. Indocyanine green angiography OD: Hypofluorescent area corresponding to the large PED and staining of the multiple sub-RPE deposits. OS: Hyperfluorescent plaque and staining of the small sub-RPE lesions as per OD. OD, right eye; OS, left eye.
The patient is observed and the subretinal and intraretinal fluid spontaneously resolves with commensurate improvement of the visual acuity consistent with the diagnosis of CSR. A meticulous systemic work-up is performed and is normal. Of note, systemic associations of CSR such as Cushing syndrome are excluded. Interestingly, with SD-OCT imaging, peculiar hyperreflective deposits are appreciated under the RPE monolayer of the PED. The authors believe that, with follow-up, these lesions erode through the RPE monolayer and are then associated with disruption of the inner and outer segments. The location of these hyperreflective deposits under the RPE and the staining characteristics with fluorescein angiography and indocyanine green angiography are characteristic of drusenoid deposits that can develop not uncommonly with CSR especially with chronic forms of CSR that can damage the RPE/Bruch complex. Hyperreflective deposits at the level of the RPE–ellipsoid level alternatively may represent shed nonphagocytosed photoreceptor segments and this has
been reported in association with CSR. These lesions hyperfluoresce with fundus autofluorescence in contrast to subretinal fibrin and lipid, and this imaging analysis would therefore be contributory in this case. I am not convinced that the original lesions that are sub-RPE represent those that are above the RPE with subsequent follow-up imaging. Choroidal imaging with enhanced depth imaging SD-OCT would help to confirm the diagnosis of CSR in this interesting patient, although in Figure 2B, the choroid is visualized and does not appear to be thickened. Serum cortisol levels to rule out a systemic etiology for the aggressive case of CSR would also be helpful. Other causes of bilateral PED that can be considered would include neovascular age-related macular degeneration and polypoidal choroidal vasculopathy that would be unlikely, given the favorable natural history of this case and the lack of choroidal neovascularization or polyps appreciated with SD-OCT or angiography. Best’s disease can cause bilateral PEDs and an electrooculogram may be helpful to exclude this diagnosis. Systemic etiologies such as paraproteinemias
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
were excluded by the authors, and the SD-OCT appearance in this case was not consistent with systemic lymphoma. Editor’s Note: Drs. De Salvo, Keane, and Tufail present a 50-yearold Turkish woman with bilateral blurred vision, decreased vision, and PED. Dr. Sarraf has consulted on this case. Dr. Sarraf believes that the fluorescein angiographic findings (comma-shaped leak), indocyanine green angiographic findings (dilated choroidal vessels), spontaneous resolution with commensurate visual improvement, and hyperreflective deposits are consistent with a diagnosis of CSR. He calls for autofluorescent imaging, noting that these hyperreflective lesions would hyperfluoresce because they represent shed nonphagocytosed photoreceptor segments, another finding consistent with CSR. He notes other causes of bilateral PED: age-related macular degeneration, idiopathic polypoidal choroidal
377
vasculopathy, Best’s disease, paraproteinemias, and lymphoma. However, Dr. Sarraf believes that the favorable natural history in this case rules out agerelated macular degeneration and the lack of polyps on OCT or angiography rules out PCV. He believes an electrooculogram would help exclude Best’s disease. He discounts lymphoma on the basis of OCT findings and acknowledges that the authors have ruled out paraproteinemias. We thank Drs. De Salvo, Keane, and Tufail for their case, and Dr. Sarraf for his analysis. RETINAÒ, The Journal of Retinal and Vitreous Diseases, encourages readers to submit Diagnostic and Therapeutic Challenges to [email protected]. Cases for the Diagnostic and Therapeutic Challenges section should include a detailed history of the patient, the diagnosis, the workup, the management, and finally, the question or questions that the submitter wishes to have answered by the consultants.
Edited by H. Richard McDonald
Drs. Gabriella De Salvo, Pearse A. Keane, Adnan Tufail, and David Sarraf
T
the small sub-RPE lesions. No evidence of vasculitis, disk leakage, or idiopathic polypoidal choroidal neovascularization was seen. B-scan ultrasonography demonstrated that total ocular coat thickness was within the normal range. Routine blood testing (including complete blood count, renal and liver function, serum angiotensin converting enzyme, and inflammatory markers) was unremarkable, as was a chest x-ray. Autoantibody testing and thyroid function was also within normal limits. In view of the unexplained hyperreflective areas distributed around the posterior pole, the patient was referred for further systemic investigations to exclude the possibility of a paraneoplastic syndrome. Clinical examinations of the chest, breast, abdomen, and lymph nodes were normal. Total body positron emission tomography (PET) and computed tomography scans were arranged and both came back normal with no evidence of malignancy. Six months after her initial presentation, her visual acuity was 6/12 in the right eye and 6/18 in the left eye. The subretinal and intraretinal fluid had resolved spontaneously, although the left eye showed an area of hyperreflectivity because of fibrosis. In the right eye, the sub-PED hyperreflective areas were now pushing the PED upward (Figure 2B). Eighteen months after her initial presentation, her best-corrected visual acuity was 6/9 in the right eye and 6/6 in the left eye. A repeat OCT again showed enlargement of bilateral PEDs and persistent multifocal hyperreflective areas under the RPE. These lesions were now migrating toward the outer nuclear layer causing disruption of the RPE, ellipsoid, and external limiting membrane (Figure 2C). Further investigations were performed, including dexamethasone suppression testing to exclude Cushing disease. These were all normal. The case is presented here for discussion of image interpretation and differential diagnosis.
his case is submitted by Dr. Gabriella De Salvo of Moorfields Eye Hospital NHS Foundation Trust, London, and University Hospital Southampton, Eye Unit, Southampton, United Kingdom; Dr. Pearse A. Keane of Moorfields Eye Hospital NHS Foundation Trust, and NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom, and UCL Institute of Ophthalmology, London, United Kingdom; and Dr. Adnan Tufail of Moorfields Eye Hospital NHS Foundation Trust; commented by Dr. David Sarraf, Los Angeles, California.
Case Report A 50-year-old Turkish woman presented to the Medical Retina Department of Moorfields Eye Hospital complaining of 2 months of bilateral blurred vision. She had a medical history of hypertension, treated with amlodipine and bendroflumethiazide, and hypercholesterolemia, treated with simvastatin. Both conditions were well controlled. On examination, her best-corrected visual acuity in the right eye was 3/60 and in her left eye was 6/24. Anterior segment examination was within normal limits. There were neither cells nor haze in the vitreous of either eye. Fundus examination showed bilateral pigment epithelial detachment (PED), multiple yellowish deep lesions at the posterior pole and in the nasal quadrants, and few retinal folds (Figure 1). Optical coherence tomography (OCT) showed bilateral large PEDs, with overlying subretinal fluid, and hyporeflective pseudocysts in the outer retinal layer. Within the PED and also outside the PED, but still underneath the retinal pigment epithelium (RPE), multiple small areas of hyperreflectivity were seen (Figure 2A). Fluorescein angiography and indocyanine green angiography were performed (Figure 3). The fluorescein angiography of the right eye showed pooling of the PED and multiple areas of staining at the level of the sub-RPE deposits, both beneath and around the PED. Indocyanine green angiography of the right eye showed a hypofluorescent area corresponding to the large PED and staining of the sub-RPE deposits. The left eye showed a similar pattern, but also with late “comma”-shaped leakage at the fovea. Indocyanine green angiography showed clearly a hyperfluorescent plaque and again staining of
Dr. David Sarraf (Los Angeles, California): De Salvo et al describe a very interesting case of a 50-year-old hypertensive Turkish woman who presents with significant bilateral vision loss. Spectral domain optical coherence tomography (SDOCT) demonstrates large PEDs with associated intraretinal and subretinal fluid in each eye. Fluorescein angiography confirms the presence of a very large serous PED with associated pooling central in the right eye and central leakage in a “comma”-shaped pattern in the left eye suggestive 374
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
375
Fig. 1. Fundus photograph showing bilateral PED and multiple yellowish deep deposits at the posterior pole and in the nasal quadrants.
of central serous retinopathy (CSR). In addition, there is multifocal staining of drusenoid deposits in each eye. The indocyanine angiogram demonstrates dilated
choroidal vessels in the right eye again suggestive of CSR, and also demonstrates staining of the drusenoid deposits in both eyes.
Fig. 2. Optical coherence tomography through the fovea (superior images) and superior to the fovea (inferior images). A. Bilateral PED with a hyporeflective area above the RPE and hyporeflective pseudocysts in the outer retinal layer. Hyporeflectivity anterior to the choriocapillaris with multiple small dots of hyperreflectivity, especially visualized in the inferior images. B. Resolved subretinal and intraretinal fluid. OD: SubPED hyperreflectivity spots are now “pushing” upward the PED. OS: Subretinal hyperreflectivity because of fibrosis, outer retinal tubulation, small residual PED in the inferior image. C. Bilateral PED and persistent multifocal hyperreflective dots under the RPE/PED migrating toward the outer nuclear layer with disruption of the RPE, ellipsoid, and external limiting membrane. OD, right eye; OS, left eye.
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RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES 2015 VOLUME 35 NUMBER 2
Fig. 3. Fluorescein angiography OD: Pooling of dye at the PED and staining at the level of the multiple sub-RPE deposits, both underneath and outside the PED. OS: Same as OD but late leakage from a hyperfluorescent foveal lesion. Indocyanine green angiography OD: Hypofluorescent area corresponding to the large PED and staining of the multiple sub-RPE deposits. OS: Hyperfluorescent plaque and staining of the small sub-RPE lesions as per OD. OD, right eye; OS, left eye.
The patient is observed and the subretinal and intraretinal fluid spontaneously resolves with commensurate improvement of the visual acuity consistent with the diagnosis of CSR. A meticulous systemic work-up is performed and is normal. Of note, systemic associations of CSR such as Cushing syndrome are excluded. Interestingly, with SD-OCT imaging, peculiar hyperreflective deposits are appreciated under the RPE monolayer of the PED. The authors believe that, with follow-up, these lesions erode through the RPE monolayer and are then associated with disruption of the inner and outer segments. The location of these hyperreflective deposits under the RPE and the staining characteristics with fluorescein angiography and indocyanine green angiography are characteristic of drusenoid deposits that can develop not uncommonly with CSR especially with chronic forms of CSR that can damage the RPE/Bruch complex. Hyperreflective deposits at the level of the RPE–ellipsoid level alternatively may represent shed nonphagocytosed photoreceptor segments and this has
been reported in association with CSR. These lesions hyperfluoresce with fundus autofluorescence in contrast to subretinal fibrin and lipid, and this imaging analysis would therefore be contributory in this case. I am not convinced that the original lesions that are sub-RPE represent those that are above the RPE with subsequent follow-up imaging. Choroidal imaging with enhanced depth imaging SD-OCT would help to confirm the diagnosis of CSR in this interesting patient, although in Figure 2B, the choroid is visualized and does not appear to be thickened. Serum cortisol levels to rule out a systemic etiology for the aggressive case of CSR would also be helpful. Other causes of bilateral PED that can be considered would include neovascular age-related macular degeneration and polypoidal choroidal vasculopathy that would be unlikely, given the favorable natural history of this case and the lack of choroidal neovascularization or polyps appreciated with SD-OCT or angiography. Best’s disease can cause bilateral PEDs and an electrooculogram may be helpful to exclude this diagnosis. Systemic etiologies such as paraproteinemias
DIAGNOSTIC AND THERAPEUTIC CHALLENGES
were excluded by the authors, and the SD-OCT appearance in this case was not consistent with systemic lymphoma. Editor’s Note: Drs. De Salvo, Keane, and Tufail present a 50-yearold Turkish woman with bilateral blurred vision, decreased vision, and PED. Dr. Sarraf has consulted on this case. Dr. Sarraf believes that the fluorescein angiographic findings (comma-shaped leak), indocyanine green angiographic findings (dilated choroidal vessels), spontaneous resolution with commensurate visual improvement, and hyperreflective deposits are consistent with a diagnosis of CSR. He calls for autofluorescent imaging, noting that these hyperreflective lesions would hyperfluoresce because they represent shed nonphagocytosed photoreceptor segments, another finding consistent with CSR. He notes other causes of bilateral PED: age-related macular degeneration, idiopathic polypoidal choroidal
377
vasculopathy, Best’s disease, paraproteinemias, and lymphoma. However, Dr. Sarraf believes that the favorable natural history in this case rules out agerelated macular degeneration and the lack of polyps on OCT or angiography rules out PCV. He believes an electrooculogram would help exclude Best’s disease. He discounts lymphoma on the basis of OCT findings and acknowledges that the authors have ruled out paraproteinemias. We thank Drs. De Salvo, Keane, and Tufail for their case, and Dr. Sarraf for his analysis. RETINAÒ, The Journal of Retinal and Vitreous Diseases, encourages readers to submit Diagnostic and Therapeutic Challenges to [email protected]. Cases for the Diagnostic and Therapeutic Challenges section should include a detailed history of the patient, the diagnosis, the workup, the management, and finally, the question or questions that the submitter wishes to have answered by the consultants.
