Retinal nerve fiber layer thinning in Parkinson disease
Open accessAbstract
Retinal dopamine loss in Parkinson disease (PD) is reflected by visual neurophysiological dysfunction. We measured the thickness of the circumpapillary retinal nerve fiber layer (RNFL) in PD patients using optical coherence tomography. The thickness in the inferior quadrant of PD patients (147 +/- 20 microns) was significantly thinner than that of controls (173 +/- 12 microns; p=0.002), while the inferotemporal area was the thinnest (146 +/- 24 vs. 191 +/- 21 microns; p=0.0003). The results show significant loss of RNFL thickness in PD at specific sites.
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PD is a motor disorder associated with degeneration of dopaminergic neurons in the substantia nigra.
“As mentioned above, PD is a motor disorder associated with degeneration of dopaminergic neurons in the substantia nigra (Inzelberg et al., 2004).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Inzelberg et al., 2004
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ResultDopaminergic Retinal Cell Loss and Visual Dysfunction in Parkinson Disease
Ortuño‐Lizarán, I., Sánchez‐Sáez, X., Lax, P., Serrano, G. E., Beach, T. G., Adler, C. H., & Cuenca, N. (2020) · Annals of Neurology · doi:10.1002/ana.25897 · Cited by 110 · see citing works
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“However, these studies examined fewer patients with lower resolution time-domain OCT. Inzelberg et al (9) and Moschos et al (5) also found selective thinning of RNFL in the temporal quadrant, whereas other reports documented thinning in the superior (8), inferior (5,9), and nasal (8) quadrants.”
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Pillai, J. A., Bermel, R. A., Bonner‐Jackson, A., Rae-Grant, A. D., Fernandez, H. H., Bena, J., Jones, S. E., Ehlers, J. P., & Leverenz, J. B. (2016) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317515628053 · Cited by 105 · see citing works
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“This is in contrast to some older and smaller studies that reported RNFL thinning using time domain OCT technology.(21,22,54) One of these also found an inverse correlation between foveal retinal thickness and the UPDRS.”
ResultOptical Coherence Tomography Angiography in Neurodegenerative Diseases: A Review
Tsokolas, G., Tsaousis, K. T., Diakonis, V. F., Matsou, A., & Tyradellis, S. (2020) · Eye and Brain · doi:10.2147/eb.s193026 · Cited by 101 · see citing works
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“The Cirrus SD-OCT (Carl Zeiss Meditec Inc., Dublin, CA) macular GC-IPL thickness algorithm has the advantage of segmenting the layers automatically and provides 8-parameter measurements rather than average thickness alone.”
BackgroundInfluentialThe optic nerve: A “mito-window” on mitochondrial neurodegeneration
Maresca, A., Morgia, C. L., Caporali, L., Valentino, M. L., & Carelli, V. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.08.004 · Cited by 92 · see citing works
L ‐DOPA‐Coated Manganese Oxide Nanoparticles as Dual MRI Contrast Agents and Drug‐Delivery Vehicles
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Melanopsin-mediated pupil function is impaired in Parkinson’s disease
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Oculo‐visual abnormalities in Parkinson's disease: Possible value as biomarkers
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“Several lines of evidence corroborate the use of OCT parameters as biomarkers of PD, with good correlations of individual retinal layer thickness and macular volume with disease severity, duration, and quality of life, although these results are somewhat controversial.(96,155,157,167,178,179) Furthermore, the RNFL app…”
ResultPerimetric and retinal nerve fiber layer findings in patients with Parkinson’s disease
Tsironi, E. E., Δαστιρίδου, Ά., Katsanos, A., Dardiotis, E., Veliki, S., Patramani, G., Zacharaki, F., Ralli, S., & Hadjigeorgiou, G. M. (2012) · BMC Ophthalmology · doi:10.1186/1471-2415-12-54 · Cited by 88 · see citing works
“A number of previous studies [10-12], although not all [14-16], provided evidence of reduced RNFL thickness in PD patients.”
BackgroundResultPeripapillary retinal nerve fiber layer thickness in bipolar disorder
Mehraban, A., Ardestani, S. M. S., Entezari, M., Seifi, M. H., Nazari, M., & Yaseri, M. (2015) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-015-2981-7 · Cited by 87 · see citing works
“OCT which was initially used for assessment of glaucoma and macular disorders [15], is currently applied in neurological disorders including multiple sclerosis [12, 16–19], Alzheimer [20], and Parkinson [21].”
MethodOptical coherence tomography indices of structural retinal pathology in schizophrenia
Silverstein, S. M., Paterno, D., Cherneski, L., & Green, S. A. (2017) · Psychological Medicine · doi:10.1017/s0033291717003555 · Cited by 86 · see citing works
“2014), where reduced input due to loss of DA-containing amacrine cells is thought to lead to loss of axons and cell bodies in other retinal cells (Inzelberg et al. 2004).”
BackgroundResultNeuro-ophthalmic disease and optical coherence tomography: glaucoma look-alikes
Pasol, J. (2011) · Current Opinion in Ophthalmology · doi:10.1097/icu.0b013e328343c1a3 · Cited by 86 · see citing works
Larrosa, J. M., García‐Martín, E., BAMBO, M., Pinilla, J., Polo, V., Otín, S., Satué, M., Herrero, R., & Pablo, L. E. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-13629 · Cited by 85 · see citing works
Polo, V., García‐Martín, E., BAMBO, M., Pinilla, J., Larrosa, J. M., Satué, M., Otín, S., & Pablo, L. E. (2014) · Eye · doi:10.1038/eye.2014.51 · Cited by 84 · see citing works
Development of a prediction formula of Parkinson disease severity by optical coherence tomography
Jiménez, B., Ascaso, F. J., Cristóbal, J. Á., & del Val, J. L. (2013) · Movement Disorders · doi:10.1002/mds.25747 · Cited by 83 · see citing works
“We are yet to see important advances being made in the search for an early diagnosis for PD.”
BackgroundInfluentialAdam, C. R., Shrier, E. M., Ding, Y., Glazman, S., & Bodis-Wollner, I. G. (2013) · Journal of Neuro-Ophthalmology · doi:10.1097/wno.0b013e31828c4e1a · Cited by 83 · see citing works
Polo, V., Satué, M., Rodrigo, M. J., Otín, S., Alarcia, R., BAMBO, M., FUERTES, M., Larrosa, J. M., Pablo, L. E., & García‐Martín, E. (2016) · BMJ Open · doi:10.1136/bmjopen-2015-009658 · Cited by 83 · see citing works
Optical coherence tomography as a tool to evaluate retinal changes in Parkinson's disease
Mailankody, P., Battu, R., Khanna, A., Lenka, A., Yadav, R., & Pal, P. K. (2015) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2015.08.002 · Cited by 82 · see citing works
Multiple retinal anomalies in schizophrenia
Adams, S. A., & Nasrallah, H. A. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2017.07.018 · Cited by 81 · see citing works
Kalenderoğlu, A., Çelik, M., Sevgi-Karadag, A., & Eğilmez, O. B. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.06.039 · Cited by 81 · see citing works
“In these studies, degeneration in retina parallel to disease severity was detected (Armarcegui et al., 2010; Inzelberg et al., 2004).”
Correlation Between Structural and Functional Retinal Changes in Parkinson Disease
Kaur, M., Saxena, R., Singh, D., Behari, M., Sharma, P., & Menon, V. (2015) · Journal of Neuro-Ophthalmology · doi:10.1097/wno.0000000000000240 · Cited by 79 · see citing works
“Keeping in mind the conflicting reports in literature regarding visual field changes in patients with PD, it is likely that fields remain preserved at least in the mild-to-moderate stages of the disease (3,8,17).”
BackgroundResultYıldız, M., Alim, S., Batmaz, S., Demir, S., Songur, E., Ortak, H., & Demirci, K. (2016) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2016.04.011 · Cited by 79 · see citing works
“OCT has been used in various neurodegenerative diseases in recent years, and RNFL thinning has been demonstrated to correlate with the disease severity in Parkinson Disease (PD) (Inzelberg et al., 2004), Alzheimer Disease (AD) (Lu et al., 2010), and Multiple Sclerosis (MS) (Petzold et al., 2010).”
BackgroundOptical Coherence Tomography in Parkinson's Disease: Is the Retina a Biomarker?
Lee, J., Ahn, J., Kim, T. W., & Jeon, B. S. (2014) · Journal of Parkinson s Disease · doi:10.3233/jpd-130306 · Cited by 78 · see citing works
“The significantly involved regions were different among the studies with the inferotemporal [44, 45], temporal [46, 47], nasal [48], diffuse area [40, 49–52], inferior nasal and temporal [53], and both inferotemporal and superotemporal and inferior [54] regions undergoing thinning in PD.”
Links among glaucoma, neurodegenerative, and vascular diseases of the central nervous system
Nucci, C., Martucci, A., Cesareo, M., Garaci, F. G., Morrone, L. A., Russo, R., Corasaniti, M. T., Bagetta, G., & Mancino, R. (2015) · Progress in brain research · doi:10.1016/bs.pbr.2015.04.010 · Cited by 78 · see citing works
Ascaso, F. J., CABEZON, L., Quintanilla, M. Á., Gutiérrez-Galve, L., López‐Antón, R., Cristóbal, J. Á., & Lobo, A. (2010) · The European Journal of Psychiatry · doi:10.4321/s0213-61632010000400005 · Cited by 75 · see citing works
“Mean ± SD [53-110] [80-143] [40-141] [41-111] [26-91]”
Interocular Asymmetry of Foveal Thickness in Parkinson Disease
Shrier, E. M., Adam, C. R., Spund, B., Glazman, S., & Bodis-Wollner, I. G. (2012) · Journal of Ophthalmology · doi:10.1155/2012/728457 · Cited by 74 · see citing works
“Ganglion cells and their axons (nerve fibers) and other inner retinal neuronal elements are pushed aside and are hence absent from the foveola.”
BackgroundMeasures of Retinal Structure and Function as Biomarkers in Neurology and Psychiatry
Silverstein, S. M., Demmin, D. L., Schallek, J. B., & Fradkin, S. I. (2020) · Biomarkers in Neuropsychiatry · doi:10.1016/j.bionps.2020.100018 · Cited by 74 · see citing works
“OCT in PD - Evidence suggests that reduced dopaminergic input to retinal ganglion cells in PD may result in degeneration (Inzelberg et al., 2004; Tian et al., 2011); thus, a growing number of studies have investigated retinal structural changes in PD using OCT.”
The awakening of artistic creativity and Parkinson's disease.
Inzelberg, R. (2013) · Behavioral Neuroscience · doi:10.1037/a0031052 · Cited by 73 · see citing works
Satué, M., Obís, J., Alarcia, R., Orduna, E., Rodrigo, M. J., Viladés, E., Gracia, H., Otín, S., Fuertes, M. I., Polo, V., et al. (2017) · Current Eye Research · doi:10.1080/02713683.2017.1370116 · Cited by 72 · see citing works
Optical coherence tomography (OCT) in optic neuritis and multiple sclerosis
Lamirel, C., Newman, N. J., & Biousse, V. (2010) · Revue Neurologique · doi:10.1016/j.neurol.2010.03.024 · Cited by 71 · see citing works
“Similarly, a few studies suggested decreased average RNFL in patients with Parkinson disease compared with age matched controls, but its correlation with disease duration or disability remains debated (Altintas et al., 2008; Hajee et al., 2009; Inzelberg et al., 2004; Jeon et al., 2006).”
BackgroundRemodeling of the fovea in Parkinson disease
Spund, B., Ding, Y., Liu, T., Selesnick, I., Glazman, S., Shrier, E. M., & Bodis-Wollner, I. G. (2012) · Journal of Neural Transmission · doi:10.1007/s00702-012-0909-5 · Cited by 71 · see citing works
Localized Retinal Nerve Fiber Layer Defects and Stroke
Wang, D., Yang, L., Wang, C., Xu, L., You, Q. S., Wang, Y. X., Zhao, L., Wei, W. B., Zhao, X., & Jonas, J. B. (2014) · Stroke · doi:10.1161/strokeaha.113.004629 · Cited by 69 · see citing works
Casas, P., Ascaso, F. J., Vicente, E. E., Tejero-Garcés, G., Adiego, M. I., & Cristóbal, J. Á. (2013) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-013-2268-9 · Cited by 68 · see citing works
Retinal correlates of neurological disorders
Yap, T. E., Balendra, S. I., Almonte, M. T., & Cordeiro, M. F. (2019) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622319882205 · Cited by 68 · see citing works
Retina thickness in Parkinson's disease and essential tremor
Cubo, E., Tedejo, R. P., Méndez, V. R., Peña, M. J. L., & y Galán, J. M. T. G. (2010) · Movement Disorders · doi:10.1002/mds.23215 · Cited by 67 · see citing works
Knoll, B., Simonett, J. M., Volpe, N. J., Farsiu, S., Ward, M., RADEMAKER, A. W., Weıntraub, S., & Fawzi, A. A. (2016) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2016.07.004 · Cited by 67 · see citing works
Nowacka, B., Lubiński, W., Honczarenko, K., Potemkowski, A., & Safranow, K. (2015) · Documenta Ophthalmologica · doi:10.1007/s10633-015-9503-0 · Cited by 66 · see citing works
“Keywords Parkinson’s disease Retinal bioelectrical function and structure ERG OCT B. Nowacka (&) W. Lubiński Department of Ophthalmology, Pomeranian Medical University, Powstancow Wlkp. 72, 70-111 Szczecin, Poland e-mail: barbara_nowacka@vp.pl K. Honczarenko Department of Neurology, Pomeranian Medical University, Szc…”
BackgroundInfluentialSharma, S., Chitranshi, N., Wall, R. V., Basavarajappa, D. K., Gupta, V., Mirzaei, M., Graham, S. L., Klistorner, A. I., & You, Y. (2021) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2021.06.001 · Cited by 66 · see citing works
Structural and functional changes in the retina in Parkinson’s disease
Alves, J., Westner, B. U., Højlund, A., Weil, R. S., & Dalal, S. S. (2023) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2022-329342 · Cited by 64 · see citing works
Eraslan, M., Çerman, E., Balci, S. Y., Çeliker, H., Şahin, Ö., Temel, A., Süer, D., & Elmacı, N. T. (2015) · Acta Ophthalmologica · doi:10.1111/aos.12809 · Cited by 64 · see citing works
“It has also been proposed that choroidal thickness is affected by age, refractive abnormalities, axial length, gender, central corneal thickness, smoking and/or ethnicity (Ramrattan et al. 1994; Inzelberg et al. 2004; Altintas et al. 2008; Fujiwara et al. 2009; Sizmaz et al. 2013; Lee et al. 2014).”
BackgroundFoveal vision is impaired in Parkinson's disease
Bodis-Wollner, I. G. (2012) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2012.07.012 · Cited by 64 · see citing works
“(2004) in 10 patients [89].”
ResultVenturing into the no‐man's land of the retina in Parkinson's disease
Bodis-Wollner, I. G., Miri, S., & Glazman, S. (2013) · Movement Disorders · doi:10.1002/mds.25741 · Cited by 60 · see citing works
In Vivo Evaluation of Retinal Neurodegeneration in Patients with Multiple Sclerosis
Tátrai, E., Simó, M., Iljicsov, A., Németh, J., DeBuc, D. C., & Somfai, G. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030922 · Cited by 60 · see citing works
Bannai, D., Lizano, P. L., Kasetty, M. A., Lutz, O., Zeng, V., Sarvode, S., Kim, L. A., Hill, S. K., Tamminga, C. A., Clementz, B. A., et al. (2020) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2020.111061 · Cited by 59 · see citing works
“Changes in retinal structure have been studied in various neurologic disorders, such as Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, and stroke (Chan et al., 2018; Inzelberg et al., 2004; Osiac et al., 2014; Petzold et al., 2017).”
BackgroundAdvances in GBA-associated Parkinson's disease – Pathology, presentation and therapies
Barkhuizen, M., Anderson, D. G., & Grobler, A. (2015) · Neurochemistry International · doi:10.1016/j.neuint.2015.12.004 · Cited by 58 · see citing works
“…of the retinal nerve fibre layer (measured by optical coherence tomography) and glaucomatous-like perimetric defects has been observed by numerous authors in PD, DLB and PD-associated dementia (Altintaş et al., 2008; Inzelberg et al., 2004; Moreno-Ramos et al., 2012; Tsironi et al., 2012).”
Abnormal visual activation in Parkinson's disease patients
Cardoso, E. F., Fregni, F., Maia, F. M., Melo, L. M., Sato, J. R., Cruz, A. C., Bianchi, E. T., Fernandes, D. B., Monteiro, M. L. R., Barbosa, E. R., et al. (2010) · Movement Disorders · doi:10.1002/mds.23101 · Cited by 58 · see citing works
“A recent study using in vivo retinal imaging in PD patients showed significant peripapillary ‘‘retinal nerve fiber layer’’ losses, providing a morphological evidence for retinal ganglion cell impairment.(16,17) In 1978, Bodis-Wollner and Yahr described a delay in VEP latency to sinusoidal gratings at mid-spatial frequ…”
BackgroundGlaucoma as a Neurodegenerative Disease Caused by Intrinsic Vulnerability Factors
Artero‐Castro, A., Rodríguez-Jiménez, F. J., Jendelová, P., VanderWall, K. B., Meyer, J. S., & Erceg, S. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101817 · Cited by 58 · see citing works
Retinal nerve changes in patients with tremor dominant and akinetic rigid Parkinson’s disease
Rohani, M., Langroodi, A. S., Ghourchian, S., Falavarjani, K. G., Soudi, R., & Shahidi, G. A. (2012) · Neurological Sciences · doi:10.1007/s10072-012-1125-7 · Cited by 56 · see citing works
“Optical coherence tomography (OCT) is a non-invasive, reproducible, easy and rapid instrument without any complications for measurement of axonal degeneration that can be a valuable measure for assessment of probable neuroprotective treatments in clinical trials and a scale for understanding the progression rate of ne…”
BackgroundResultDoes retina play a role in Parkinson's Disease?
Devi, S. M., Iyer, M., Aswathy, N. P., Dhivya, V., & Vellingiri, B. (2020) · Acta Neurologica Belgica · doi:10.1007/s13760-020-01274-w · Cited by 56 · see citing works
Dopamine, Alpha-Synuclein, and Mitochondrial Dysfunctions in Parkinsonian Eyes
Indrieri, A., Pizzarelli, R., Franco, B., & Leonibus, E. D. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.567129 · Cited by 56 · see citing works
The Effect of Levodopa and Dopamine Agonists on Optic Nerve Head in Parkinson Disease
Yavaş, G. F., YILMAZ, O., Küsbeci, T., & Öztürk, F. (2007) · European Journal of Ophthalmology · doi:10.1177/112067210701700520 · Cited by 55 · see citing works
“Inzelberg et al (17) evaluated the peripapillary RNFL using optical coherence tomography and showed that the thickness in the inferior quadrant of patients with PD was significantly thinner compared to control subjects.”
Primary vision and facial emotion recognition in early Parkinson's disease
Hipp, G., Diederich, N. J., Pieria, V., & Vaillant, M. (2014) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2013.12.047 · Cited by 54 · see citing works
- Authors
- Inzelberg, R., Ramirez, J. A., Nisipeanu, P., & Ophir, A.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Hillel Yaffe Medical Center (IL)
- Corresponding author
- Ophir, Avinoam
- ORCID
- Inzelberg, Rivka
- Venue
- Vision Research
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 44
- Issue
- 24
- Pages
- 2793-2797
- ISSN
- 0042-6989 (ISSN-L)
- OpenAlex
- W1974244012
- Cited by
- 343
- References
- 17
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 15 · 2023: 13 · 2022: 25 · 2021: 15 · 2020: 30 · 2019: 20 · 2018: 21 · 2017: 26 · 2016: 21 · 2015: 27 · 2014: 23 · 2013: 21 · 2012: 22
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Vision Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health, State of Israel
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Keywords
- Parkinson's disease, retinal nerve fiber layer, retinal nerve fiber layer thickness, optic nerve head, retinal neurodegeneration
- MeSH terms
- Adult, Aged, Female, Humans, Male, Middle Aged, Nerve Fibers, Parkinson Disease, Retina, Tomography, Optical Coherence
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