- Email: [email protected]
We cannot see what she cannot ignore
Accepted Manuscript We cannot see what she cannot ignore Francesco Pellegrini, MD, Emanuela Interlandi, MD, PhD, Carlos Pavesio, MD, Henry A. Ferreyra, MD PII:
S0039-6257(17)30042-5
DOI:
10.1016/j.survophthal.2017.02.001
Reference:
SOP 6704
To appear in:
Survey of Ophthalmology
Received Date: 26 January 2017 Accepted Date: 6 February 2017
Please cite this article as: Pellegrini F, Interlandi E, Pavesio C, Ferreyra HA, We cannot see what she cannot ignore, Survey of Ophthalmology (2017), doi: 10.1016/j.survophthal.2017.02.001. 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.
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We cannot see what she cannot ignore
Francesco Pellegrini, MD (1)
RI PT
Emanuela Interlandi, MD PhD (1) Carlos Pavesio, MD (2)
SC
Henry A. Ferreyra, MD (3)
Moorfields Eye Hospital, London, UK.
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(2)
M AN U
(1) Neuro-Ophthalmology Service, Department of Ophthalmology, “De Gironcoli” Hospital, Conegliano, Italy
AC C
EP
(3) Shiley Eye Institute, Department of Ophthalmology, University of California, San Diego, La Jolla, California, USA
address correspondence to: Francesco Pellegrini
Address: Via D. Manin 110, Conegliano (TV) Italy, tel: +39 0438 668111
+39 0438 668362
email: [email protected]
ACCEPTED MANUSCRIPT
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M AN U
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(In keeping with the format of a clinical pathologic conference, the abstract and key words appear at the end of the article)
EP
Case Report
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A 32-year-old woman presented with the acute onset of a small scotoma in the right visual field. Visual acuity (VA) was 20/20 OU, and the slit lamp examination of both anterior and posterior segments was normal. Optical coherence tomography (OCT) and fluorescein angiography (FA) performed the same day were interpreted as normal. Retrobulbar optic neuritis was suspected, but a contrast enhanced brain magnetic resonance imaging (MRI) performed one week later showed no signs of optic neuritis
ACCEPTED MANUSCRIPT
or multiple sclerosis. She was sent to our neuro-ophthalmology service for a second opinion.
RI PT
We examined the patient one month after onset. Her past ocular history was unremarkable. She denied smoking, trauma, or a recent flu-like illness. She had discontinued an anxiolytic drug, but she had started oral
SC
contraceptives the week before the onset of visual symptoms. Her VA was
M AN U
20/20 OU, pupils were equal and briskly reactive to light with no relative afferent pupillary defect. The anterior segment was normal, and fundus examination was unremarkable OU (Fig.1). Ishihara color plates were
TE D
named correctly OU, and there was no red desaturation. Humphrey 24-2 automated static perimetry was normal bilaterally, while the Amsler grid
EP
revealed a small, well-defined drop-shaped scotoma adjacent to central
AC C
fixation in the right eye (Fig. 2). What are your thoughts and what would you do first? Comments
Comments by Henry Ferreyra, MD Although the patient’s fundus and imaging were initially interpreted as normal, the Amsler grid identified a well-defined scotoma. I would use the
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location of the scotoma to direct where I would look for pathology. Before embarking on functional testing, such as multifocal electroretinography and microperimetry, I would look carefully for subtle anatomic changes in
Case Report (Continued)
RI PT
the corresponding region on the spectral-domain OCT.
SC
The previous FA was indeed normal, but her first OCT (Fig. 3) actually
M AN U
revealed a small, but definite, hyperreflective lesion in the outer retina in
What is the next step?
TE D
the right macula with focal disruption of the ellipsoid zone (EZ)
EP
Comments (Continued)
AC C
Comments by Dr. Ferreyra I would use other imaging modalities, such as fundus autofluorescence, infrared (IR) photography, and red-free photography to further characterize the pathology. Functional testing, such as microperimetry and multifocal electroretinography could also be used to objectively assess the extent of the scotoma.
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Case Report (Continued) Macular OCT was repeated (Fig.4, bottom) and revealed a mild disruption
RI PT
of the junction between the EZ and RPE/Bruch membrane complex. On Near IR (NIR) images (Fig.4, top) a small but well defined drop shaped dark area was evident superiorly and temporally from the fovea and
SC
adjacent to it, well matching her Amsler grid. Multifocal electroretinogram
M AN U
(Fig. 5) and microperimetry revealed a depression in sensitivity in that site compared to other areas of the macula. Fundus autofluorescence and infrared autofluorescence were normal.
TE D
What diagnosis do you consider at this point?
Comments (Continued)
EP
Comments by Henry Ferreyra
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The patient’s history of an acute onset, paracentral scotoma and corresponding findings of a drop-shaped dark area visible on IR photography associated with hyper-reflectivity at the level of the outer nuclear layer (ONL) and outer plexiform layer (OPL) with disruption of underlying
ellipsoid
zone
is
consistent
with
acute
macular
neuroretinopathy (AMN), also known as paracentral acute middle
ACCEPTED MANUSCRIPT
maculopathy (PAMM), with a type 2 lesion. In contrast, PAMM with a type 1 lesion is associated with a hyper-reflective plaque at the junction of
unaffected EZ. Case Report (Concluded)
RI PT
the OPL and inner nuclear layer (INL) extending into the INL and with an
SC
A diagnosis of AMN was made based on the positive history of oral
M AN U
contraceptives, exclusion of other causes of a scotoma, and the results of retinal imaging in the setting of normal biomicroscopic retinal evaluation. At one year follow up the patient denies new visual symptoms, but still can
EP
TE D
detect a dark drop-shaped scotoma in the right visual field.
Discussion
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AMN, first described by Bos and Deutman in 1975,1,4 has a typical acute onset of photopsias and paracentral scotomas associated with mild visual impairment. Fundus examination usually discloses reddish-brown and wedge-shaped macular lesions with apices directed toward the fovea, often in a petalloid or tear-drop configuration.8 In less than 6% of cases, however, fundus examination is normal.2,4 Rarely macular edema and
ACCEPTED MANUSCRIPT
retinal hemorrhages can be seen.3,7 AMN mostly affects young white nonLatino women and may be unilateral or bilateral. Its pathogenesis remains unclear, but several studies with spectral-domain OCT (SD-OCT) suggest
RI PT
ischemia of the deep retinal capillary plexus as a possible pathogenic mechanism.5,6 Risk factors for AMN would also suggest a retinal vascular
SC
etiology; in fact over one-third of patients report oral contraceptive use.
M AN U
In AMN, SD-OCT localizes the lesion below the OPL in the acute phase, resulting in late ONL atrophy. FA and indocyanine green angiography , on the contrary, are unremarkable in most cases, although they may be useful
TE D
in excluding other causes of visual loss. Recently6 a new clinical entity, PAMM, has been recognized as the development of hyper-reflective SD-
the INL.
EP
OCT lesions similar to that seen in AMN ,but more superficial, involving AMN and PAMM, however, may show some overlapping
AC C
clinical features. The case discussed here shows how difficult the diagnosis of AMN may be, particularly when the patient presents late in the course of the disease, the scotoma is small, and fundus examination does not reveal any abnormality. NIR in conjunction with SD-OCT may be the most sensitive imaging modalities to diagnose the retinal lesions in AMN since they may be abnormal even when clinical examination and
ACCEPTED MANUSCRIPT
SC
REFERENCES
RI PT
color fundus photography are unremarkable.
M AN U
1. Bos PJ, Deutman AF. Acute macular neuroretinopathy. Am J Ophthalmol. 1975;80(4):573-84
2. Fine AM et al.: Earliest symptoms caused by neovascular
TE D
membranes in the macula. Arch Ophthalmol. 1986; 104:513-514 3. Gass JD, Hamed LM. Acute macular neuroretinopathy and
EP
multiple evanescent white dot syndrome occurring in the same
AC C
patients. Arch Ophthalmol. 1989;107(2):189 e 93 4. Kavita V. Bhavsar, MD, Sally Lin, MD, Ehsan Rahimy, MD, Anthony Joseph, MD, K. Bailey Freund, MD, David Sarraf, MD,Emmett T. Cunningham, Jr. MD, PhD, MPH. Acute macular neuroretinopathy: A comprehensive review of the literature. Surv Ophthalmol. 2016 Mar 10. pii: S0039-6257(15)30057-6. doi: 10.1016/j.survophthal.2016.03.003.
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5. Rahimy E, Kuehlewein L, Sadda S, et al. Paracentral acute middle maculopathy: what we knew then and what we know now.
RI PT
Retina. 2015;35(10):1921-1930 6. Rahimy E, Sarraf D. Paracentral acute middle maculopathy
spectral-domain optical coherence tomography feature of deep
SC
capillary ischemia. Curr Opin Ophthalmol.2014;25(3):207-12
M AN U
7. Rait JL, O’Day J. Acute macular neuroretinopathy. Aust N Z J Ophthalmol. 1987;15(4):337-40
8. Turbeville SD, Cowan LD, Gass JD. Acute macular
TE D
neuroretinopathy: a review of the literature. Surv Ophthalmol.
AC C
EP
2003;48(1):1-11.
Abstract
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A 32-year-old woman presented with the acute onset of a small scotoma in the right visual field. She was initially thought to have optic neuritis, but brain magnetic resonance imaging was normal. A review of her symptoms
RI PT
and medications disclosed recent use of oral contraceptives. Near infrared imaging was the only objective abnormality, consistent with her Amsler
SC
grid changes, leading to the diagnosis of acute macular neuroretinopathy.
M AN U
Key words: acute macular neuroretinopathy; infra-red optical coherence
AC C
EP
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tomography; optic neuritis; scotoma,
SC
Fig.1. Fundus is normal in either eye.
RI PT
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Fig. 2 Amsler grid of the affected eye shows inferonasale drop shaped
M AN U
scotoma.
EP
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Fig.3. OCT of the right eye performed acutely: there is a small hyperreflective lesion under the fovea in the outer retina.
AC C
Fig. 4. IR image (top) shows a drop-shaped dark area iuxtafoveally, pointing toward the fovea. OCT scan (bottom) in the same area reveals a mild disruption in the OS/EPR junction.
Fig. 5. Multifocal ERG of the right eye shows depressed retinal response in the affected area.
AC C
EP
TE D
M AN U
SC
RI PT
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EP
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M AN U
SC
RI PT
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EP
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M AN U
SC
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M AN U
SC
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S0039-6257(17)30042-5
DOI:
10.1016/j.survophthal.2017.02.001
Reference:
SOP 6704
To appear in:
Survey of Ophthalmology
Received Date: 26 January 2017 Accepted Date: 6 February 2017
Please cite this article as: Pellegrini F, Interlandi E, Pavesio C, Ferreyra HA, We cannot see what she cannot ignore, Survey of Ophthalmology (2017), doi: 10.1016/j.survophthal.2017.02.001. 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.
ACCEPTED MANUSCRIPT
We cannot see what she cannot ignore
Francesco Pellegrini, MD (1)
RI PT
Emanuela Interlandi, MD PhD (1) Carlos Pavesio, MD (2)
SC
Henry A. Ferreyra, MD (3)
Moorfields Eye Hospital, London, UK.
TE D
(2)
M AN U
(1) Neuro-Ophthalmology Service, Department of Ophthalmology, “De Gironcoli” Hospital, Conegliano, Italy
AC C
EP
(3) Shiley Eye Institute, Department of Ophthalmology, University of California, San Diego, La Jolla, California, USA
address correspondence to: Francesco Pellegrini
Address: Via D. Manin 110, Conegliano (TV) Italy, tel: +39 0438 668111
+39 0438 668362
email: [email protected]
ACCEPTED MANUSCRIPT
TE D
M AN U
SC
RI PT
(In keeping with the format of a clinical pathologic conference, the abstract and key words appear at the end of the article)
EP
Case Report
AC C
A 32-year-old woman presented with the acute onset of a small scotoma in the right visual field. Visual acuity (VA) was 20/20 OU, and the slit lamp examination of both anterior and posterior segments was normal. Optical coherence tomography (OCT) and fluorescein angiography (FA) performed the same day were interpreted as normal. Retrobulbar optic neuritis was suspected, but a contrast enhanced brain magnetic resonance imaging (MRI) performed one week later showed no signs of optic neuritis
ACCEPTED MANUSCRIPT
or multiple sclerosis. She was sent to our neuro-ophthalmology service for a second opinion.
RI PT
We examined the patient one month after onset. Her past ocular history was unremarkable. She denied smoking, trauma, or a recent flu-like illness. She had discontinued an anxiolytic drug, but she had started oral
SC
contraceptives the week before the onset of visual symptoms. Her VA was
M AN U
20/20 OU, pupils were equal and briskly reactive to light with no relative afferent pupillary defect. The anterior segment was normal, and fundus examination was unremarkable OU (Fig.1). Ishihara color plates were
TE D
named correctly OU, and there was no red desaturation. Humphrey 24-2 automated static perimetry was normal bilaterally, while the Amsler grid
EP
revealed a small, well-defined drop-shaped scotoma adjacent to central
AC C
fixation in the right eye (Fig. 2). What are your thoughts and what would you do first? Comments
Comments by Henry Ferreyra, MD Although the patient’s fundus and imaging were initially interpreted as normal, the Amsler grid identified a well-defined scotoma. I would use the
ACCEPTED MANUSCRIPT
location of the scotoma to direct where I would look for pathology. Before embarking on functional testing, such as multifocal electroretinography and microperimetry, I would look carefully for subtle anatomic changes in
Case Report (Continued)
RI PT
the corresponding region on the spectral-domain OCT.
SC
The previous FA was indeed normal, but her first OCT (Fig. 3) actually
M AN U
revealed a small, but definite, hyperreflective lesion in the outer retina in
What is the next step?
TE D
the right macula with focal disruption of the ellipsoid zone (EZ)
EP
Comments (Continued)
AC C
Comments by Dr. Ferreyra I would use other imaging modalities, such as fundus autofluorescence, infrared (IR) photography, and red-free photography to further characterize the pathology. Functional testing, such as microperimetry and multifocal electroretinography could also be used to objectively assess the extent of the scotoma.
ACCEPTED MANUSCRIPT
Case Report (Continued) Macular OCT was repeated (Fig.4, bottom) and revealed a mild disruption
RI PT
of the junction between the EZ and RPE/Bruch membrane complex. On Near IR (NIR) images (Fig.4, top) a small but well defined drop shaped dark area was evident superiorly and temporally from the fovea and
SC
adjacent to it, well matching her Amsler grid. Multifocal electroretinogram
M AN U
(Fig. 5) and microperimetry revealed a depression in sensitivity in that site compared to other areas of the macula. Fundus autofluorescence and infrared autofluorescence were normal.
TE D
What diagnosis do you consider at this point?
Comments (Continued)
EP
Comments by Henry Ferreyra
AC C
The patient’s history of an acute onset, paracentral scotoma and corresponding findings of a drop-shaped dark area visible on IR photography associated with hyper-reflectivity at the level of the outer nuclear layer (ONL) and outer plexiform layer (OPL) with disruption of underlying
ellipsoid
zone
is
consistent
with
acute
macular
neuroretinopathy (AMN), also known as paracentral acute middle
ACCEPTED MANUSCRIPT
maculopathy (PAMM), with a type 2 lesion. In contrast, PAMM with a type 1 lesion is associated with a hyper-reflective plaque at the junction of
unaffected EZ. Case Report (Concluded)
RI PT
the OPL and inner nuclear layer (INL) extending into the INL and with an
SC
A diagnosis of AMN was made based on the positive history of oral
M AN U
contraceptives, exclusion of other causes of a scotoma, and the results of retinal imaging in the setting of normal biomicroscopic retinal evaluation. At one year follow up the patient denies new visual symptoms, but still can
EP
TE D
detect a dark drop-shaped scotoma in the right visual field.
Discussion
AC C
AMN, first described by Bos and Deutman in 1975,1,4 has a typical acute onset of photopsias and paracentral scotomas associated with mild visual impairment. Fundus examination usually discloses reddish-brown and wedge-shaped macular lesions with apices directed toward the fovea, often in a petalloid or tear-drop configuration.8 In less than 6% of cases, however, fundus examination is normal.2,4 Rarely macular edema and
ACCEPTED MANUSCRIPT
retinal hemorrhages can be seen.3,7 AMN mostly affects young white nonLatino women and may be unilateral or bilateral. Its pathogenesis remains unclear, but several studies with spectral-domain OCT (SD-OCT) suggest
RI PT
ischemia of the deep retinal capillary plexus as a possible pathogenic mechanism.5,6 Risk factors for AMN would also suggest a retinal vascular
SC
etiology; in fact over one-third of patients report oral contraceptive use.
M AN U
In AMN, SD-OCT localizes the lesion below the OPL in the acute phase, resulting in late ONL atrophy. FA and indocyanine green angiography , on the contrary, are unremarkable in most cases, although they may be useful
TE D
in excluding other causes of visual loss. Recently6 a new clinical entity, PAMM, has been recognized as the development of hyper-reflective SD-
the INL.
EP
OCT lesions similar to that seen in AMN ,but more superficial, involving AMN and PAMM, however, may show some overlapping
AC C
clinical features. The case discussed here shows how difficult the diagnosis of AMN may be, particularly when the patient presents late in the course of the disease, the scotoma is small, and fundus examination does not reveal any abnormality. NIR in conjunction with SD-OCT may be the most sensitive imaging modalities to diagnose the retinal lesions in AMN since they may be abnormal even when clinical examination and
ACCEPTED MANUSCRIPT
SC
REFERENCES
RI PT
color fundus photography are unremarkable.
M AN U
1. Bos PJ, Deutman AF. Acute macular neuroretinopathy. Am J Ophthalmol. 1975;80(4):573-84
2. Fine AM et al.: Earliest symptoms caused by neovascular
TE D
membranes in the macula. Arch Ophthalmol. 1986; 104:513-514 3. Gass JD, Hamed LM. Acute macular neuroretinopathy and
EP
multiple evanescent white dot syndrome occurring in the same
AC C
patients. Arch Ophthalmol. 1989;107(2):189 e 93 4. Kavita V. Bhavsar, MD, Sally Lin, MD, Ehsan Rahimy, MD, Anthony Joseph, MD, K. Bailey Freund, MD, David Sarraf, MD,Emmett T. Cunningham, Jr. MD, PhD, MPH. Acute macular neuroretinopathy: A comprehensive review of the literature. Surv Ophthalmol. 2016 Mar 10. pii: S0039-6257(15)30057-6. doi: 10.1016/j.survophthal.2016.03.003.
ACCEPTED MANUSCRIPT
5. Rahimy E, Kuehlewein L, Sadda S, et al. Paracentral acute middle maculopathy: what we knew then and what we know now.
RI PT
Retina. 2015;35(10):1921-1930 6. Rahimy E, Sarraf D. Paracentral acute middle maculopathy
spectral-domain optical coherence tomography feature of deep
SC
capillary ischemia. Curr Opin Ophthalmol.2014;25(3):207-12
M AN U
7. Rait JL, O’Day J. Acute macular neuroretinopathy. Aust N Z J Ophthalmol. 1987;15(4):337-40
8. Turbeville SD, Cowan LD, Gass JD. Acute macular
TE D
neuroretinopathy: a review of the literature. Surv Ophthalmol.
AC C
EP
2003;48(1):1-11.
Abstract
ACCEPTED MANUSCRIPT
A 32-year-old woman presented with the acute onset of a small scotoma in the right visual field. She was initially thought to have optic neuritis, but brain magnetic resonance imaging was normal. A review of her symptoms
RI PT
and medications disclosed recent use of oral contraceptives. Near infrared imaging was the only objective abnormality, consistent with her Amsler
SC
grid changes, leading to the diagnosis of acute macular neuroretinopathy.
M AN U
Key words: acute macular neuroretinopathy; infra-red optical coherence
AC C
EP
TE D
tomography; optic neuritis; scotoma,
SC
Fig.1. Fundus is normal in either eye.
RI PT
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Fig. 2 Amsler grid of the affected eye shows inferonasale drop shaped
M AN U
scotoma.
EP
TE D
Fig.3. OCT of the right eye performed acutely: there is a small hyperreflective lesion under the fovea in the outer retina.
AC C
Fig. 4. IR image (top) shows a drop-shaped dark area iuxtafoveally, pointing toward the fovea. OCT scan (bottom) in the same area reveals a mild disruption in the OS/EPR junction.
Fig. 5. Multifocal ERG of the right eye shows depressed retinal response in the affected area.
AC C
EP
TE D
M AN U
SC
RI PT
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EP
TE D
M AN U
SC
RI PT
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