Acta Ophthalmologica 2014
underwent visual acuity, colour vision and OCT examinations using two SDOCT devices. One hundred and fourteen eyes were evaluated: 57 eyes from patients with AD and 57 eyes from healthy subjects. To establish this cohort, we examined 65 patients with AD, but eight patients were not included in the study for the presence of unknown eye disease (two cases) or their inability to perform the full exploration protocol due to their functional status (six cases). Mean age was 75.29 8.64 years in the AD group and 74.77 9.24 years in the control group. Mean disease duration was 3.71 years (range, 1.46– 5.96 years). Age, sex and intra-ocular pressure did not differ significantly between healthy controls and patients with AD (p > 0.05). RNFL thickness measured with the two OCT devices is shown in Table 1. Cirrus OCT revealed significant RNFL thinning in patients
1
Meditec, Inc., Dublin, Ireland) and Spectralis OCT (Heidelberg Engineering, Inc., Carlsbad, CA, USA)]. To carry out this prospective, crosssectional study, 57 patients with mild or moderate AD and 57 healthy, age-matched control subjects were included. Inclusion criteria were: confirmed AD diagnosis; best-corrected visual acuity (BCVA) of 0.1 or higher; and intra-ocular pressure 5 dioptres of spherical equivalent refraction or three dioptres of astigmatism); systemic conditions that could affect the visual system and history of ocular trauma or concomitant ocular diseases. Each eye was considered separately; one eye from each subject was randomly selected to be included in the analyses, except when one of the eyes was excluded (due to the presence of significant media opacity). All subjects
doi: 10.1111/aos.12374
Table 1. Structural parameter means and standard deviation in parenthesis for retinal nerve fiber layer (RNFL) thickness obtained using the cirrus optical coherence tomography (OCT) and the two RNFL applications of Spectralis OCT (Glaucoma and Nsite Axonal analytics); and comparison between healthy controls and patients with Alzheimer disease.
Foundation Trust Manchester Academin Health Science Centre Manchester M13 9WL, UK Tel: +0161 276 5630 Fax: +0161 276 5642 Email: [email protected]
Detection of retinal nerve fiber layer degeneration in patients with Alzheimer’s disease using optical coherence tomography: searching new biomarkers Maria P Bambo,1 Elena Garcia-Martin,1,2 Juan Pinilla,1 Raquel Herrero,1 Maria Satue,1 Sofia Otin,1 Isabel Fuertes,1 Marcia L Marques3 and Luıs E Pablo1,2 Ophthalmology Department, Miguel Servet University Hospital, Zaragoza, Spain; 2Aragones Institute of Health Sciences, Zaragoza, Spain; 3Instituto de Molestias Oculares, S~ ao Paulo, Brasil
Healthy subjects
Editor, t the present time, researchers are searching for biomarkers and tools to detect the Alzheimer’s disease (AD) in early phases, especially in high-risk families, and to monitor disease progression. Recent studies have revealed degenerative changes in optic nerve fibers, causing thinning of the retinal nerve fiber layer (RNFL) in patients with AD (Berisha et al. 2007; Kirbas et al. 2013). The RNFL comprises axons originating in retinal ganglion cells and can be measured using ocular imaging technologies such as optical coherence tomography (OCT), which provides non-invasive, rapid, objective and reproducible measurements. Retrograde loss of nerve fibers in the retina and optic nerve may be an early biomarker of neurodegeneration in AD, even prior to hippocampal damage, which impacts memory (Valenti 2007). Following this trend, we conducted a study in which we compared RNFL thickness in healthy and AD subjects using the two most commonly available spectral-domain (SD)-OCT machines [Cirrus OCT (Carl Zeiss
A
Patients with AD
Cirrus OCT RNFL thickness Average 95.96 (9.5) 89.00 (10.2) Superior 121.11 (17.9) 109.12 (17.5) Nasal 71.34 (12.0) 69.33 (13.1) Inferior 126.98 (16.9) 116.63 (15.4) Temporal 63.94 (9.2) 62.77 (10.1) Spectralis OCT RNFL thickness (Glaucoma application) Average 100.71 (9.4) 96.21 (10.7) Superior 121.65 (17.9) 116.96 (18.2) Nasal 77.58 (18.2) 73.97 (16.5) Inferior 134.10 (16.9) 122.73 (17.4) Temporal 72.55 (14.8) 67.17 (18.2) Superonasal 107.29 (24.5) 105.10 (25.3) Inferonasal 116.68 (25.4) 111.65 (26.3) Inferotemporal 151.71 (15.6) 133.13 (20.0) Superotemporal 136.10 (21.1) 131.65 (25.4) Spectralis OCT RNFL thickness (Nsite Axonal application) Average 98.70 (10.1) 95.79 (10.7) Superior 121.44 (17.6) 117.33 (17.6 Nasal 75.41 (20.9) 72.7 (17.2) Inferior 130.89 (13.8) 121.77 (14.3) Temporal 69.07 (9.6) 68.21 (12.4) Superonasal 104.96 (23.1) 103.62 (20.4) Inferonasal 111.41 (21.7) 110.79 (19.7) Inferotemporal 150.56 (16.0) 132.85 (18.1) Superotemporal 137.96 (19.2) 131.46 (20.5) N/T Index 1.08 (0.3) 1.15 (0.4) PMB 54.67 (11.2) 52.37 (7.7)
p*
0.001 0.001 0.436 0.003 0.707 0.061 0.262 0.396 0.005 0.174 0.706 0.403 0.001 0.420 0.272 0.356 0.587 0.012 0.762 0.804 0.906 0.001 0.200 0.498 0.360
RNFL, retinal nerve fiber layer; AD, Alzheimer disease; OCT, optical coherence tomography; N/ T index, nasal/temporal index; PMB, papillo-macular bundle. * Statistical difference between healthy subjects and patients with Alzheimer disease for each parameter. Bold values indicate statistically significant at p < 0.05.
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with AD especially in the superior and the inferior quadrant. The Spectralis OCT classic glaucoma application and the Nsite Axonal Analytics application revealed significant thinning in the inferior and inferotemporal RNFL in patients with AD compared with controls. There is histopathologic evidence of retinal ganglion cell loss and optic nerve degeneration in patients with AD (Blanks et al. 1996). Thus, we postulate that axonal loss secondary to other pathologic changes that occur in the brain can be detected by scanning the RNFL and the optic nerve, as these nonmyelinated axons form the optical path that culminates in the occipital cortex. Although we believe the OCT could potentially provide a biomarker of AD, it should take into account a series of limitations: the relatively small sample size (despite being larger than that in previous studies) and the exclusion of subjects with mild cognitive impairment (preclinical stage of AD) or advanced dementia. Future prospective studies should attempt to segment the RNFL and macula to know which retinal layers are predominantly affected and should investigate Age Macular Disease-AD associations (by calculating amount of druse; measuring thickness of Bruch’s membrane and auto-fluorescence of retina in AD cases, etc.) (Ohno-Matsui 2011). We think this is an interesting and promising research field in an unfortunately increasingly common dementing disorder in the elderly. Time will tell whether we are only measuring and comparing different parameters with the latest technologies or whether we are facing a new and accessible biomarker of disease.
Valenti DA (2007): Neuroimaging of retinal nerve fiber layer in AD using optical coherence tomography. Neurology 69: 1060.
References
doi: 10.1111/aos.12357
Berisha F, Feke GT, Trempe CL, McMeel JW, Schepens CL (2007): Retinal abnormalities in early Alzheimer’s disease. Invest Ophthalmol Vis Sci 48: 2285–2289. Blanks JC, Torigoe Y, Hinton DR, Blanks RH (1996): Retinal pathology in Alzheimer’s disease. I. Ganglion cell loss in foveal/parafoveal retina. Neurobiol Aging 17: 377–384. Kirbas S, Turkyilmaz K, Anlar O, Tufekci A, Durmus M (2013): Retinal nerve fiber layer analysis in patients with Alzheimer’s disease. J Neuro Ophthalmol 33: 58–61. Ohno-Matsui K (2011): Parallel findings in agerelated macular degeneration and Alzheimer’s disease. Prog Retin Eye Res 30: 217–238.
e582
Correspondence: Maria P Bambo C/ Padre Arrupe Consultas Externas de Oftalmologıa 50009Zaragoza (Spain) Tel: 0034.976.76.55.58 Fax: 0034.976.76.55.09 Email: [email protected]
Relationship between breast arterial calcifications seen on screening mammograms and age-related macular degeneration Jorge Sa a,1,2 Oscar Fern andez-Guinea,2,3 3 Paz Garcıa-Pravia, Belen FernandezGarcia,2 Noemı Eir o,2 Jose M. del 2,4 Casar, Rafael Venta,5 Bego~ na Baamonde6,7 and Francisco J. Vizoso2,4 1 Servicio de Oftalmologıa, Fundaci on Hospital de Jove, Gij on, Spain; 2 Unidad de Investigaci on, Fundaci on Hospital de Jove, Gij on, Spain; 3 Servicio de Radiodiagn ostico, Fundaci on Hospital de Jove, Gij on, Spain;4Servicio de Cirugıa General, Fundaci on Hospital de Jove, Gij on, Spain; 5Servicio de An alisis Clınicos, Hospital San Agustın, Aviles, Spain; 6 Servicio de Oftalmologıa, Hospital Universitario Central de Asturias, Oviedo, Spain; 7Departamento de Cirugıa y Especialidades MedicoQuir urgicas, Universidad de Oviedo, Oviedo, Spain
Editor, ge-related macular degeneration (AMD) is a complex multifactorial disease, and several factors have been associated with its occurrence, such as age, genetic factors or cardiovascular disease. Breast arterial calcifications (BACs) are a common finding on screening mammograms (8–12%) of women (Maas et al. 2006; Pidal et al. 2009) and may be an important marker for generalized
A
vascular disease (Maas et al. 2006; Pidal et al. 2009; Ahn et al. 2011; Schnatz et al. 2011). Both BAC and AMD have some clinical and biochemical vascular risk factors in common. We revised digital mammograms and records from women, finding out that 8.5% of the total population presented BAC. Seventy-one women with BAC and 50 without BAC accepted to go into the study. Demographic and clinical evaluation, ophthalmic examination and biochemical serum analysis (plasma total homocysteine (tHcy) and high-sensitivity C-reactive protein (hs-CRP)) were performed. Each ophthalmic assessment included a 45° colour digital retinography and a macular HD-optical coherence tomography (OCT) examination. Macular area was evaluated with a standard grid template included in the retinography system. Drusen
underwent visual acuity, colour vision and OCT examinations using two SDOCT devices. One hundred and fourteen eyes were evaluated: 57 eyes from patients with AD and 57 eyes from healthy subjects. To establish this cohort, we examined 65 patients with AD, but eight patients were not included in the study for the presence of unknown eye disease (two cases) or their inability to perform the full exploration protocol due to their functional status (six cases). Mean age was 75.29 8.64 years in the AD group and 74.77 9.24 years in the control group. Mean disease duration was 3.71 years (range, 1.46– 5.96 years). Age, sex and intra-ocular pressure did not differ significantly between healthy controls and patients with AD (p > 0.05). RNFL thickness measured with the two OCT devices is shown in Table 1. Cirrus OCT revealed significant RNFL thinning in patients
1
Meditec, Inc., Dublin, Ireland) and Spectralis OCT (Heidelberg Engineering, Inc., Carlsbad, CA, USA)]. To carry out this prospective, crosssectional study, 57 patients with mild or moderate AD and 57 healthy, age-matched control subjects were included. Inclusion criteria were: confirmed AD diagnosis; best-corrected visual acuity (BCVA) of 0.1 or higher; and intra-ocular pressure 5 dioptres of spherical equivalent refraction or three dioptres of astigmatism); systemic conditions that could affect the visual system and history of ocular trauma or concomitant ocular diseases. Each eye was considered separately; one eye from each subject was randomly selected to be included in the analyses, except when one of the eyes was excluded (due to the presence of significant media opacity). All subjects
doi: 10.1111/aos.12374
Table 1. Structural parameter means and standard deviation in parenthesis for retinal nerve fiber layer (RNFL) thickness obtained using the cirrus optical coherence tomography (OCT) and the two RNFL applications of Spectralis OCT (Glaucoma and Nsite Axonal analytics); and comparison between healthy controls and patients with Alzheimer disease.
Foundation Trust Manchester Academin Health Science Centre Manchester M13 9WL, UK Tel: +0161 276 5630 Fax: +0161 276 5642 Email: [email protected]
Detection of retinal nerve fiber layer degeneration in patients with Alzheimer’s disease using optical coherence tomography: searching new biomarkers Maria P Bambo,1 Elena Garcia-Martin,1,2 Juan Pinilla,1 Raquel Herrero,1 Maria Satue,1 Sofia Otin,1 Isabel Fuertes,1 Marcia L Marques3 and Luıs E Pablo1,2 Ophthalmology Department, Miguel Servet University Hospital, Zaragoza, Spain; 2Aragones Institute of Health Sciences, Zaragoza, Spain; 3Instituto de Molestias Oculares, S~ ao Paulo, Brasil
Healthy subjects
Editor, t the present time, researchers are searching for biomarkers and tools to detect the Alzheimer’s disease (AD) in early phases, especially in high-risk families, and to monitor disease progression. Recent studies have revealed degenerative changes in optic nerve fibers, causing thinning of the retinal nerve fiber layer (RNFL) in patients with AD (Berisha et al. 2007; Kirbas et al. 2013). The RNFL comprises axons originating in retinal ganglion cells and can be measured using ocular imaging technologies such as optical coherence tomography (OCT), which provides non-invasive, rapid, objective and reproducible measurements. Retrograde loss of nerve fibers in the retina and optic nerve may be an early biomarker of neurodegeneration in AD, even prior to hippocampal damage, which impacts memory (Valenti 2007). Following this trend, we conducted a study in which we compared RNFL thickness in healthy and AD subjects using the two most commonly available spectral-domain (SD)-OCT machines [Cirrus OCT (Carl Zeiss
A
Patients with AD
Cirrus OCT RNFL thickness Average 95.96 (9.5) 89.00 (10.2) Superior 121.11 (17.9) 109.12 (17.5) Nasal 71.34 (12.0) 69.33 (13.1) Inferior 126.98 (16.9) 116.63 (15.4) Temporal 63.94 (9.2) 62.77 (10.1) Spectralis OCT RNFL thickness (Glaucoma application) Average 100.71 (9.4) 96.21 (10.7) Superior 121.65 (17.9) 116.96 (18.2) Nasal 77.58 (18.2) 73.97 (16.5) Inferior 134.10 (16.9) 122.73 (17.4) Temporal 72.55 (14.8) 67.17 (18.2) Superonasal 107.29 (24.5) 105.10 (25.3) Inferonasal 116.68 (25.4) 111.65 (26.3) Inferotemporal 151.71 (15.6) 133.13 (20.0) Superotemporal 136.10 (21.1) 131.65 (25.4) Spectralis OCT RNFL thickness (Nsite Axonal application) Average 98.70 (10.1) 95.79 (10.7) Superior 121.44 (17.6) 117.33 (17.6 Nasal 75.41 (20.9) 72.7 (17.2) Inferior 130.89 (13.8) 121.77 (14.3) Temporal 69.07 (9.6) 68.21 (12.4) Superonasal 104.96 (23.1) 103.62 (20.4) Inferonasal 111.41 (21.7) 110.79 (19.7) Inferotemporal 150.56 (16.0) 132.85 (18.1) Superotemporal 137.96 (19.2) 131.46 (20.5) N/T Index 1.08 (0.3) 1.15 (0.4) PMB 54.67 (11.2) 52.37 (7.7)
p*
0.001 0.001 0.436 0.003 0.707 0.061 0.262 0.396 0.005 0.174 0.706 0.403 0.001 0.420 0.272 0.356 0.587 0.012 0.762 0.804 0.906 0.001 0.200 0.498 0.360
RNFL, retinal nerve fiber layer; AD, Alzheimer disease; OCT, optical coherence tomography; N/ T index, nasal/temporal index; PMB, papillo-macular bundle. * Statistical difference between healthy subjects and patients with Alzheimer disease for each parameter. Bold values indicate statistically significant at p < 0.05.
e581
Acta Ophthalmologica 2014
with AD especially in the superior and the inferior quadrant. The Spectralis OCT classic glaucoma application and the Nsite Axonal Analytics application revealed significant thinning in the inferior and inferotemporal RNFL in patients with AD compared with controls. There is histopathologic evidence of retinal ganglion cell loss and optic nerve degeneration in patients with AD (Blanks et al. 1996). Thus, we postulate that axonal loss secondary to other pathologic changes that occur in the brain can be detected by scanning the RNFL and the optic nerve, as these nonmyelinated axons form the optical path that culminates in the occipital cortex. Although we believe the OCT could potentially provide a biomarker of AD, it should take into account a series of limitations: the relatively small sample size (despite being larger than that in previous studies) and the exclusion of subjects with mild cognitive impairment (preclinical stage of AD) or advanced dementia. Future prospective studies should attempt to segment the RNFL and macula to know which retinal layers are predominantly affected and should investigate Age Macular Disease-AD associations (by calculating amount of druse; measuring thickness of Bruch’s membrane and auto-fluorescence of retina in AD cases, etc.) (Ohno-Matsui 2011). We think this is an interesting and promising research field in an unfortunately increasingly common dementing disorder in the elderly. Time will tell whether we are only measuring and comparing different parameters with the latest technologies or whether we are facing a new and accessible biomarker of disease.
Valenti DA (2007): Neuroimaging of retinal nerve fiber layer in AD using optical coherence tomography. Neurology 69: 1060.
References
doi: 10.1111/aos.12357
Berisha F, Feke GT, Trempe CL, McMeel JW, Schepens CL (2007): Retinal abnormalities in early Alzheimer’s disease. Invest Ophthalmol Vis Sci 48: 2285–2289. Blanks JC, Torigoe Y, Hinton DR, Blanks RH (1996): Retinal pathology in Alzheimer’s disease. I. Ganglion cell loss in foveal/parafoveal retina. Neurobiol Aging 17: 377–384. Kirbas S, Turkyilmaz K, Anlar O, Tufekci A, Durmus M (2013): Retinal nerve fiber layer analysis in patients with Alzheimer’s disease. J Neuro Ophthalmol 33: 58–61. Ohno-Matsui K (2011): Parallel findings in agerelated macular degeneration and Alzheimer’s disease. Prog Retin Eye Res 30: 217–238.
e582
Correspondence: Maria P Bambo C/ Padre Arrupe Consultas Externas de Oftalmologıa 50009Zaragoza (Spain) Tel: 0034.976.76.55.58 Fax: 0034.976.76.55.09 Email: [email protected]
Relationship between breast arterial calcifications seen on screening mammograms and age-related macular degeneration Jorge Sa a,1,2 Oscar Fern andez-Guinea,2,3 3 Paz Garcıa-Pravia, Belen FernandezGarcia,2 Noemı Eir o,2 Jose M. del 2,4 Casar, Rafael Venta,5 Bego~ na Baamonde6,7 and Francisco J. Vizoso2,4 1 Servicio de Oftalmologıa, Fundaci on Hospital de Jove, Gij on, Spain; 2 Unidad de Investigaci on, Fundaci on Hospital de Jove, Gij on, Spain; 3 Servicio de Radiodiagn ostico, Fundaci on Hospital de Jove, Gij on, Spain;4Servicio de Cirugıa General, Fundaci on Hospital de Jove, Gij on, Spain; 5Servicio de An alisis Clınicos, Hospital San Agustın, Aviles, Spain; 6 Servicio de Oftalmologıa, Hospital Universitario Central de Asturias, Oviedo, Spain; 7Departamento de Cirugıa y Especialidades MedicoQuir urgicas, Universidad de Oviedo, Oviedo, Spain
Editor, ge-related macular degeneration (AMD) is a complex multifactorial disease, and several factors have been associated with its occurrence, such as age, genetic factors or cardiovascular disease. Breast arterial calcifications (BACs) are a common finding on screening mammograms (8–12%) of women (Maas et al. 2006; Pidal et al. 2009) and may be an important marker for generalized
A
vascular disease (Maas et al. 2006; Pidal et al. 2009; Ahn et al. 2011; Schnatz et al. 2011). Both BAC and AMD have some clinical and biochemical vascular risk factors in common. We revised digital mammograms and records from women, finding out that 8.5% of the total population presented BAC. Seventy-one women with BAC and 50 without BAC accepted to go into the study. Demographic and clinical evaluation, ophthalmic examination and biochemical serum analysis (plasma total homocysteine (tHcy) and high-sensitivity C-reactive protein (hs-CRP)) were performed. Each ophthalmic assessment included a 45° colour digital retinography and a macular HD-optical coherence tomography (OCT) examination. Macular area was evaluated with a standard grid template included in the retinography system. Drusen
