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Clinical Sciences |

Inner Retinal Layer Thinning in Parkinson Disease FREE

Mohammedyusuf E. Hajee, MD; Wayne F. March, MD; Douglas R. Lazzaro, MD; Arthur H. Wolintz, MD; Eric M. Shrier, DO; Sofya Glazman, MD; Ivan G. Bodis-Wollner, MD, DSc
[+] Author Affiliations

Author Affiliations: Departments of Neurology, State University of New York Downstate Medical Center (Drs Hajee, Wolintz, Glazman, and Bodis-Wollner), Parkinson Disease and Related Disorders Center of Excellence, State University of New York Downstate (Dr Bodis-Wollner) and Kingsbrook Jewish Medical Center (Dr Bodis-Wollner); and Departments of Ophthalmology, State University of New York Downstate Medical Center (Drs Hajee, March, Lazzaro, Wolintz, Shrier, and Bodis-Wollner), Long Island College Hospital (Drs Hajee, March, Lazzaro, and Shrier), and Kingsbrook Jewish Medical Center (Drs Hajee and Wolintz), Brooklyn, New York.


Arch Ophthalmol. 2009;127(6):737-741. doi:10.1001/archophthalmol.2009.106.
Text Size: A A A
Published online

Objective  To quantify retinal thickness in patients with Parkinson disease (PD).

Methods  Forty-five eyes of 24 PD patients and 31 eyes of 17 control subjects underwent a comprehensive ophthalmologic examination. We used optical coherence tomography to examine retinal thickness, separately quantifying the inner and outer retinal layers. Intraocular pressure was measured by Goldmann applanation tonometry.

Results  The mean (SD) ages of the patients with PD and healthy subjects were 64.0 (6.5) years vs 63.5 (10.7) years (P = .77). The mean (SD) intraocular pressure was 13.6 (+/−2.7) mm Hg in the PD patients. No difference was found in either the superior or inferior outer retinal layer thickness of PD vs control eyes. The mean (SD) superior inner retinal layer thickness of PD vs control eyes was 88.79 (11.3) μm vs 103.5 (24.3) μm (P = .01), and the mean inferior inner retinal layer thickness was 89.83 (11.1) μm vs 104.0 (23.5) μm (P = .01).

Conclusions  The inner retinal layer is significantly thinner in PD patients than in healthy subjects. Idiopathic PD, distinct from glaucoma, needs to be considered in the differential diagnosis of retinal nerve fiber layer thinning.

Figures in this Article

Parkinson disease (PD) is a common neurodegenerative disease characterized by a loss of dopaminergic neurons in the basal ganglia–substantia nigra pars compacta of the midbrain; this disease affects 1% of adults older than 60 years in the United States.1 It was originally described in 1817 by James Parkinson as “shaking palsy.”2 However, it has been progressively recognized that PD also affects the autonomic, olfactory, and visual systems.3,4 Initially, the evidence of visual deficit in PD was obtained by functional measurements, such as the visual evoked potential5 and contrast sensitivity (CS).6 It was shown that the human retina contains dopaminergic amacrine cells7 and that retinal dopamine content and metabolites are substantially lowered in PD patients.8,9 However, direct functional evidence of retinal involvement in PD first emerged from electroretinography.10,11 Pattern electroretinographic (PERG) responses in humans12 with idiopathic PD were similar to those obtained in the monkey model of PD13 and in the monkey eye treated with intraocular 6-hydroxydopamine,14 a known toxin of dopaminergic neurons.

Recently, direct morphologic evidence of retinal involvement in PD emerged from time-domain optical coherence tomography (OCT).1517 Inzelberg et al18 first reported significant peripapillary retinal nerve fiber layer losses in 10 patients and Altintas et al19 most recently confirmed this in another 17 patients. In our study, we used Fourier-domain OCT, with superior resolution and stability, compared with the earlier OCT (time-domain) method. We evaluated the inner retinal layer (IRL) and outer retinal layer (ORL) in each eye and measured intraocular pressures (IOPs) as a potential contributing variable for retinal thinning. The results show that the IRL is thin in patients with relatively early PD and the loss of nerve fiber layer in patients with PD is not secondary to increased IOP.

STUDY PARTICIPANTS

Consecutive patients who were diagnosed as having idiopathic PD, based on the accepted UK Brain Bank criteria,20 were enrolled in the study by neurologists with a special interest in PD. Exclusion criteria were coincident posterior-pole disease, such as macular degeneration or any optic neuropathy due to glaucoma or ischemic optic neuropathy. The erythrocyte sedimentation rate, a potentially relevant laboratory value, was normal in all study participants. The presumptive diagnosis of glaucoma was based on a history of the use of glaucoma medications, increased cupping of the optic nerve, elevated IOP (>21 mm Hg), and/or glaucomatous visual field defects. All study participants had a best-corrected visual acuity of 20/30 or better. Thirteen patients had Humphrey 30-2 visual field tested. The area of the retina evaluated by our OCT corresponds to the central/paracentral area of the visual field. None of the patients showed central/paracentral scotoma on routine visual field testing. Nine patients had their baseline ophthalmologic examination performed by ophthalmologists who provided their routine care, whereas the other patients underwent a comprehensive ophthalmologic examination by one of the coinvestigator ophthalmologists (W.F.M.) involved in this study. We studied 46 consecutive eyes of 23 PD patients. All PD patients enrolled were relatively early in their disease course, with an average duration of 2.9 years. The mean (SD) ages of the healthy subjects and PD patients were 63.5 (10.7) years and 64.0 (6.52) years (P = .77). Twelve (52%) of the PD patients were undergoing pharmacologic therapies that had stabilized their disease, whereas 11 had not yet been treated with dopaminergic agents (de novo patients). Of the treated PD patients, 7 were treated with presynaptic (levodopa) medications, 4 were taking a combination of levodopa and a dopamine receptor agonist, and 1 was taking pramipexole alone. Their disease stages21 ranged from 2 to 3, with a mean of 2.5.

EQUIPMENT AND MEASUREMENTS

We used Fourier-domain OCT (RTvue; Optovue, Inc; Fremont, California) with an imaging speed of approximately 25 000 axial scans per second, which is approximately 50 times faster than time-domain detection.17 One of the many advantages of this high speed is that it can allow the transformation from 2-dimensional to 3-dimensional imaging. The overall image quality of Fourier-domain OCT is also superior because of the elimination of many motion artifacts from the increased speed of acquisition. This is particularly relevant in PD patients with tremor. The axial resolution of a time-domain OCT is 8 to 10 μm, whereas for Fourier-domain OCT it is approximately 5 μm, which results in a more accurate representation of retinal topography.

Because a PD OCT protocol does not exist, the standard glaucoma protocol, which includes Nerve Head Map (NHM4) and Macula Map (MM7) scans (Optovue, Inc), was performed for all PD patients. The IRL includes the nerve fiber layer, the ganglion cell layer, and the inner-plexiform layer, whereas the ORL includes the layers starting from the inner nuclear layer up to and including the retinal pigment epithelium. The retinal layer measurements were 6 × 6-mm sections of the macula. Scans with artifacts such as motion and media were eliminated. Eyes of healthy (control) subjects were examined in the same way.

STATISTICAL ANALYSIS

Statistical analysis was performed using descriptive statistics and analyses of variance. To assess the reproducibility of data obtained with our instrument, we compared 2 consecutive OCT measurements in 7 healthy controls (13 eyes) in 1-week intervals. The mean IRL change was 1.25 μm. These data compare favorably with the stability data of Optovue, which claim an average variation of only 5 μm. The variability obtained with our equipment is comparable with results obtained with other equipment, such as Heidelberg retinal tomography devices.22

In Figure 1 and Figure 2 we show the retina of a healthy individual and a patient with PD, respectively, who are roughly the same age. The paramacular area from where measurements were taken is indicated in millimeters.

Place holder to copy figure label and caption
Figure 1.

The retina of a healthy individual. IRL indicates inner retinal layer; ORL, outer retinal layer.

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Place holder to copy figure label and caption
Figure 2.

The retina of a patient with Parkinson disease. IRL indicates inner retinal layer; ORL, outer retinal layer.

Graphic Jump Location
INFERIOR AND SUPERIOR IRL THICKNESSES

The mean (SD) inferior IRL thickness of healthy eyes vs PD eyes was 104.0 (23.5) μm vs 89.83 (11.1) μm (P = .01). The mean superior IRL thickness of healthy eyes vs PD eyes was 103.5 (24.3) μm vs 88.79 (11.3) μm (P = .01). Clearly, the inferior and superior IRLs are similarly affected in PD patients, and the paramacular inner retina is approximately 15% thinner than the retina of PD patients in age-matched control subjects (Table).

Table Graphic Jump LocationTable. The Retinal Thickness of Healthy Individuals vs Those of PD Patientsa
ORL THICKNESS

The ORL thickness was also analyzed in the same manner as the IRL. The mean (SD) superior ORL thickness of healthy eyes vs PD eyes was 170.2 (+/−23.8) μm vs 170.4 (+/−7.67) μm (P =0.88). The mean (SD) inferior ORL thickness of healthy eyes vs PD eyes was 168.2 (+/−22.9) μm vs 167.9 (+/−7.86) μm (P = 0.99). A factorial analysis of variance (general linear model) was used to examine if the difference between the right and left eye was dependent on PD diagnosis using the interaction between 2 factors: laterality (right, left eye) and PD diagnosis (PD, no PD). This interaction was not significant for either the superior or inferior IRL or ORL (Table).

INTEROCULAR COMPARISON OF IRL THICKNESS IN EARLY PD

Figure 3 illustrates a correlation between the left and right eyes of patients with relatively early PD. The corresponding statistics revealed a correlation coefficient of 0.82. Figure 4 shows a correlation between the left and right IRL thickness of patients with relatively early PD. The corresponding statistics revealed a correlation coefficient of 0.82.

Place holder to copy figure label and caption
Figure 3.

Correlation between the inner retinal layer thickness of the left and right eyes of patients with relatively early Parkinson disease (r = 0.31). IRL indicates inner retinal layer; ORL, outer retinal layer.

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Place holder to copy figure label and caption
Figure 4.

Correlation between the inner retinal layer (IRL) thickness of the left and right eyes of patients with relatively early Parkinson disease (r = 0.82).

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CORRELATION BETWEEN MEAN IRL AND ORL IN EARLY PD

An insignificant correlation was also found between IRL and ORL thickness in the eyes of patients with relatively early PD. The corresponding statistics revealed a correlation coefficient of 0.33.

THE EFFECT OF TREATMENT

The mean (SD) superior nerve fiber layer thickness measurements of the treated eyes and untreated eyes were 87.0 (+/−11.17) μm and 91.05 (+/−7.14) μm (P = 0.25), respectively. The mean (SD) inferior IRL thickness measurements of the treated eyes and untreated eyes were 89.51(+/−9.52) μm and 91.04 (+/−8.12) μm (P = 0.67), respectively. The mean (SD) superior ORL thickness measurements of the treated eyes and untreated eyes were 171.8 (+/−5.59) μm and 168.7 (+/−9.8 μm) (P = 0.20), respectively. The mean (SD) inferior ORL thickness of the treated eyes and untreated eyes was 169.2 (+/−6.02) μm and 164.4 (+/−10.01) μm (P = 0.45), respectively.

DISEASE DURATION AND IOP

The time elapsed from PD diagnosis compared with the severity of retinal findings was not statistically significant (P = .11). The mean (SD) IOP was 13.6 (+/−2.7) mm Hg in PD patients. The correlation of IOP to nerve fiber layer thickness was not statistically significant (r = 0.26, P = .034).

Our study demonstrates a thinning of the IRL in the macular region in PD eyes. Inzelberg et al18 reported a stronger effect in the inferior peripapillary quadrant. Our results in PD suggest that the mean thickness of both superior and inferior macular hemispheres is roughly equal. However, looking at individual results, we found that 58% of the superior and 73% of the inferior IRL thickness of PD eyes fell outside 1 SD. When studying the same patients in 1.5 SDs, 47% of the superior PD IRL and 62% of inferior PD IRL fell outside the range. Clearly, a further comparison of inferior and superior IRL is needed for the paramacular region in a larger number of patients.

Recently, Altintas et al19 reported on the correlation of disease severity with inner foveal but without macular or peripapillary thickness in 17 PD eyes. We examined a 6-mm macular section, which correlates with 17° of central vision. The IRL contains both the ganglion and the amacrine cell layers and is approximately 15% to 20% thinned in this region of the PD retina. Perhaps this modest loss is the reason for the absence of disc pallor in PD despite ganglion cell damage, a result also demonstrated by Yavas et al.22 However, the 15% to 20% loss in total IRL thickness does not necessarily cause a minor loss as far as vision is concerned.

Although visual acuity is only minimally affected in patients with well-corrected PD, they lose foveal CS to patterns to which healthy observers are most sensitive (need the least contrast to detect).6,23 However, levodopa treatment improves CS.24

The PERG is a measure of retinal ganglion cell activity.25,26 In both PD and the monkey model, PERG shows a specific spatial frequency deficit12,13 similar to the spatial frequency selective CS loss in PD. Spatial frequency is one standard measure of the fineness or coarseness of the visual stimulus; it consists of alternating dark and bright bands (grating pattern). In healthy observers and monkeys, when PERG response or contrast sensitivity is plotted against spatial frequency, the resulting curve is nonmonotonic: it shows a peak that represents the best visible spatial frequency pattern. This is called spatial frequency tuning. Tuning reflects the interplay of antagonistic center or surround organization of foveal ganglion cell receptive fields.27 Tuning is attenuated or absent in CS or PERG in PD patients. On the basis of the effects of selective D1 and D2 receptor blockers on PERG of the monkey, we28,29 modeled the preganglionic dopaminergic circuit, which modulates the balance of center and surrounds the organization of foveal ganglion cells of the primate. The model quantifies the way that dopaminergic amacrine cells, although sparsely distributed, control the tuning of foveal ganglion cells via separate D1- and D2-linked receptors and the way that dopaminergic amacrine cell dysfunction may result in absent spatial frequency tuning.29

Retinal thinning may be relevant to the early diagnosis and neuroprotective treatment of PD. Most of our patients were in the early stages of the disease. On the basis of the distribution of Lewy bodies at different stages of PD, Braak et al30 suggested that PD progresses from peripheral to central neurons in a caudocranial direction. It has not been investigated whether Lewy bodies are found in the human retina of PD patients. It needs to be established whether OCT measures contribute a quantitative measure to the early diagnosis of PD other than a constellation of early signs.31

The OCT results in PD are potentially relevant for the ophthalmologist. The IRL thinning has been reported in other diseases, such as primary open-angle glaucoma,32 multiple sclerosis,33,34 and Alzheimer disease.35,36 The IOP is raised in glaucoma, whereas in our PD patients the IOP was normal. In Alzheimer disease retinal thinning is predominant only in the superior quadrant.35,36 In summary, Fourier-domain OCT may contribute a quantitative imaging approach to the early diagnosis, treatment, and follow-up of progression of PD.

Correspondence: Ivan G. Bodis-Wollner, MD, DSc, Department of Ophthalmology and Department of Neurology, Parkinson's Disease and Related Disorders Center of Excellence, State University of New York–Downstate, 450 Clarkson Ave, Brooklyn, NY 11203 (ivan.bodis-wollner@downstate.edu).

Submitted for Publication: May 15, 2008; final revision received January 6, 2009; accepted January 15, 2009.

Financial Disclosure: None reported.

Funding/Support: This study was funded by the National Parkinson Foundation. Dr Hajee was supported by an Empire Clinical Research Investigator Program–New York State Research Fellowship/Mentor Grant.

Additional Contributions: Hans Von Gizycki, PhD, provided statistical consultation. Zoya Belakovskaya, BS, and Mr. Alexander Belakovski provided technical support. Nancy Blace, MD, PhD, performed preliminary data collection. Muhammad Javaid, MD, assisted with graph preparations. Manuela E. Minko, MD, assisted in scheduling patients. Patricia Kavanagh, MD, referred and recruited patients. Hossam Attia, MD, performed a preliminary study comparing GDx Nerve Fiber Analyzer measures in patients with glaucoma and PD; he and Preeti Poley, MD, performed preliminary Glaucoma Diagnosis data collection.

Korell  MTanner  C Epidemiology of Parkinson's disease. Ebadi  MPfeiffer  RParkinson's Disease New York, NY CRC Press2005;39- 50
Parkinson  J An Essay on the Shaking Palsy. J Neuropsychiatry Clin Neurosci 2002;14 (5) 223- 236
Link to Article
Appenzeller  OGoss  JE Autonomic deficits in Parkinson's syndrome. Arch Neurol 1971;24 (1) 50- 57
PubMed Link to Article
Korten  JJMeulstee  J Olfactory disturbances in Parkinsonism. Clin Neurol Neurosurg 1980;82 (2) 113- 118
PubMed Link to Article
Bodis-Wollner  IYahr  MD Measurement of visual evoked potentials in Parkinson's disease. Brain 1978;1661- 671
Link to Article
Bodis-Wollner  IMarx  MSMitra  S  et al.  Visual dysfunction in Parkinson's disease: loss in spatiotemporal contrast sensitivity. Brain 1987;110 (pt 6) 1675- 1698
PubMed Link to Article
Frederick  JMRayborn  MELaties  AMLam  DMHollyfield  JG Dopaminergic neurons in the human retina. J Comp Neurol 1982;210 (1) 65- 79
PubMed Link to Article
Harnois  CDi Paolo  T Decreased dopamine in the retinas of patients with Parkinson's disease. Invest Ophthalmol Vis Sci 1990;31 (11) 2473- 2475
PubMed
Djamgoz  MBHankins  MWHirano  JArcher  SN Neurobiology of retinal dopamine in relation to degenerative states of the tissue. Vision Res 1997;37 (24) 3509- 3529
PubMed Link to Article
Ikeda  HHead  GMEllis  CJ Electrophysiological signs of retinal dopamine deficiency in recently diagnosed Parkinson's disease and a follow up study. Vision Res 1994;34 (19) 2629- 2638
PubMed Link to Article
Sartucci  FOrlandi  GLucetti  C  et al.  Changes in pattern electroretinograms to equiluminant red-green and blue-yellow gratings in patients with early Parkinson's disease. J Clin Neurophysiol 2003;20 (5) 375- 381
PubMed Link to Article
Tagliati  MBodis-Wollner  IYahr  MD The pattern electroretinogram in Parkinson's disease reveals lack of retinal spatial tuning. Electroencephalogr Clin Neurophysiol 1996;100 (1) 1- 11
Link to Article
Ghilardi  MFBodis-Wollner  IOnofrj  MC  et al.  Spatial frequency dependent abnormalities of the pattern electroretinogram and visual evoked potentials in a parkinsonian monkey model. Brain 1988;111131- 149
PubMed Link to Article
Ghilardi  MFMarx  MSBodis-Wollner  ICamras  CBGlover  AA The effect of intraocular 6-hydroxydopamine on retinal processing of primates. Ann Neurol 1989;25 (4) 357- 364
PubMed Link to Article
Schuman  JSPedut-Kloizman  THertzmark  E  et al.  Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography. Ophthalmology 1996;103 (11) 1889- 1898
PubMed Link to Article
Blumenthal  EZWilliams  JMWeinreb  RNGirkin  CABerry  CCZangwill  LM Reproducibility of nerve fiber layer thickness measurements by use of optical coherence tomography. Ophthalmology 2000;107 (12) 2278- 2282
PubMed Link to Article
Wojtkowski  MSrinivasan  VFujimoto  J  et al.  Three-dimensional retinal imaging with high speed ultrahigh resolution optical coherence tomography. Ophthalmology 2005;112 (10) 1734- 1746
PubMed Link to Article
Inzelberg  RRamirez  JANisipeanu  POphir  A Retinal nerve fiber layer thinning in Parkinson disease. Vision Res 2004;44 (24) 2793- 2797
PubMed Link to Article
Altintas  OIseri  POzkan  BCaglar  Y Correlation between retinal morphological and functional findings and clinical severity in Parkinson's disease. Doc Ophthalmol 2008;116 (2) 137- 146
PubMed Link to Article
Daniel  SELees  AJ Parkinson's Disease Society Brain Bank, London: overview and research. J Neural Transm Suppl 1993;39165- 172
PubMed
Hoehn  MMYahr  MD Parkinsonism: onset, progression and mortality. Neurology 1967;17427- 442
Link to Article
Yavas  GFYilmaz  OKüsbeci  TOztürk  F The effect of levodopa and dopamine agonists on optic nerve head in Parkinson disease. Eur J Ophthalmol 2007;17 (5) 812- 816
PubMed
Bodis-Wollner  I Visual deficits related to dopamine deficiency in experimental animals and Parkinson's disease patients. Trends Neurosci 1990;13 (7) 296- 302
PubMed Link to Article
Hutton  JTMorris  JLElias  JW Levodopa improves spatial contrast sensitivity in Parkinson's disease. Arch Neurol 1993;50721- 724
Link to Article
Maffei  LFiorentini  ABisti  SHolländer  H Pattern ERG in the monkey after section of the optic nerve. Exp Brain Res 1985;59 (2) 423- 425
PubMed Link to Article
Bobak  PBodis-Wollner  IHarnois  C  et al.  Pattern electroretinograms and visual-evoked potentials in glaucoma and multiple sclerosis. Am J Ophthalmol 1983;96 (1) 72- 83
PubMed
Enroth-Cugell  CRobson  JG The contrast sensitivity of retinal ganglion cells of the cat. J Physiol 1966;187 (3) 517- 552
Bodis-Wollner  ITzelepi  A The push-pull action of dopamine on spatial tuning of the monkey retina: the effects of dopaminergic deficiency and selective D1 and D2 receptor ligands on the pattern electroretinogram. Vision Res 1998;38 (10) 1479- 1487
PubMed Link to Article
Bodis-Wollner  ITzelepi  A The effect of diverse dopamine receptors on spatial processing in the central retina: a model. Jenkin  MHarris  LSeeing Spatial Form New York, NY Oxford University Press2005;347- 367
Braak  HDel Tredici  KBratzke  H  et al.  Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson's disease (preclinical and clinical stages). J Neurol 2002;249 (suppl 3) 1- 5
Link to Article
Bodis-Wollner  I Diagnosing and treating early: is there a pre-cardinal stage of Parkinson disease? Parkinson Report 2008;199- 10
Lalezary  MMedeiros  FAWeinreb  RN  et al.  Baseline optical coherence tomography predicts the development of glaucomatous change in glaucoma suspects. Am J Ophthalmol 2006;142 (4) 576- 582
PubMed Link to Article
Fisher  JBJacobs  DAMarkowitz  CE  et al.  Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology 2006;113 (2) 324- 332
PubMed Link to Article
Pulicken  MGordon-Lipkin  EBalcer  LJFrohman  ECutter  GCalabresi  PA Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 2007;69 (22) 2085- 2092
PubMed Link to Article
Berisha  FFeke  GTTrempe  CLMcMeel  JWSchepens  CL Retinal abnormalities in early Alzheimer's disease. Invest Ophthalmol Vis Sci 2007;48 (5) 2285- 2289
PubMed Link to Article
Valenti  DA Neuroimaging of retinal nerve fiber layer in AD using optical coherence tomography. Neurology 2007;69 (10) 1060
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

The retina of a healthy individual. IRL indicates inner retinal layer; ORL, outer retinal layer.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

The retina of a patient with Parkinson disease. IRL indicates inner retinal layer; ORL, outer retinal layer.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Correlation between the inner retinal layer thickness of the left and right eyes of patients with relatively early Parkinson disease (r = 0.31). IRL indicates inner retinal layer; ORL, outer retinal layer.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.

Correlation between the inner retinal layer (IRL) thickness of the left and right eyes of patients with relatively early Parkinson disease (r = 0.82).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable. The Retinal Thickness of Healthy Individuals vs Those of PD Patientsa

References

Korell  MTanner  C Epidemiology of Parkinson's disease. Ebadi  MPfeiffer  RParkinson's Disease New York, NY CRC Press2005;39- 50
Parkinson  J An Essay on the Shaking Palsy. J Neuropsychiatry Clin Neurosci 2002;14 (5) 223- 236
Link to Article
Appenzeller  OGoss  JE Autonomic deficits in Parkinson's syndrome. Arch Neurol 1971;24 (1) 50- 57
PubMed Link to Article
Korten  JJMeulstee  J Olfactory disturbances in Parkinsonism. Clin Neurol Neurosurg 1980;82 (2) 113- 118
PubMed Link to Article
Bodis-Wollner  IYahr  MD Measurement of visual evoked potentials in Parkinson's disease. Brain 1978;1661- 671
Link to Article
Bodis-Wollner  IMarx  MSMitra  S  et al.  Visual dysfunction in Parkinson's disease: loss in spatiotemporal contrast sensitivity. Brain 1987;110 (pt 6) 1675- 1698
PubMed Link to Article
Frederick  JMRayborn  MELaties  AMLam  DMHollyfield  JG Dopaminergic neurons in the human retina. J Comp Neurol 1982;210 (1) 65- 79
PubMed Link to Article
Harnois  CDi Paolo  T Decreased dopamine in the retinas of patients with Parkinson's disease. Invest Ophthalmol Vis Sci 1990;31 (11) 2473- 2475
PubMed
Djamgoz  MBHankins  MWHirano  JArcher  SN Neurobiology of retinal dopamine in relation to degenerative states of the tissue. Vision Res 1997;37 (24) 3509- 3529
PubMed Link to Article
Ikeda  HHead  GMEllis  CJ Electrophysiological signs of retinal dopamine deficiency in recently diagnosed Parkinson's disease and a follow up study. Vision Res 1994;34 (19) 2629- 2638
PubMed Link to Article
Sartucci  FOrlandi  GLucetti  C  et al.  Changes in pattern electroretinograms to equiluminant red-green and blue-yellow gratings in patients with early Parkinson's disease. J Clin Neurophysiol 2003;20 (5) 375- 381
PubMed Link to Article
Tagliati  MBodis-Wollner  IYahr  MD The pattern electroretinogram in Parkinson's disease reveals lack of retinal spatial tuning. Electroencephalogr Clin Neurophysiol 1996;100 (1) 1- 11
Link to Article
Ghilardi  MFBodis-Wollner  IOnofrj  MC  et al.  Spatial frequency dependent abnormalities of the pattern electroretinogram and visual evoked potentials in a parkinsonian monkey model. Brain 1988;111131- 149
PubMed Link to Article
Ghilardi  MFMarx  MSBodis-Wollner  ICamras  CBGlover  AA The effect of intraocular 6-hydroxydopamine on retinal processing of primates. Ann Neurol 1989;25 (4) 357- 364
PubMed Link to Article
Schuman  JSPedut-Kloizman  THertzmark  E  et al.  Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography. Ophthalmology 1996;103 (11) 1889- 1898
PubMed Link to Article
Blumenthal  EZWilliams  JMWeinreb  RNGirkin  CABerry  CCZangwill  LM Reproducibility of nerve fiber layer thickness measurements by use of optical coherence tomography. Ophthalmology 2000;107 (12) 2278- 2282
PubMed Link to Article
Wojtkowski  MSrinivasan  VFujimoto  J  et al.  Three-dimensional retinal imaging with high speed ultrahigh resolution optical coherence tomography. Ophthalmology 2005;112 (10) 1734- 1746
PubMed Link to Article
Inzelberg  RRamirez  JANisipeanu  POphir  A Retinal nerve fiber layer thinning in Parkinson disease. Vision Res 2004;44 (24) 2793- 2797
PubMed Link to Article
Altintas  OIseri  POzkan  BCaglar  Y Correlation between retinal morphological and functional findings and clinical severity in Parkinson's disease. Doc Ophthalmol 2008;116 (2) 137- 146
PubMed Link to Article
Daniel  SELees  AJ Parkinson's Disease Society Brain Bank, London: overview and research. J Neural Transm Suppl 1993;39165- 172
PubMed
Hoehn  MMYahr  MD Parkinsonism: onset, progression and mortality. Neurology 1967;17427- 442
Link to Article
Yavas  GFYilmaz  OKüsbeci  TOztürk  F The effect of levodopa and dopamine agonists on optic nerve head in Parkinson disease. Eur J Ophthalmol 2007;17 (5) 812- 816
PubMed
Bodis-Wollner  I Visual deficits related to dopamine deficiency in experimental animals and Parkinson's disease patients. Trends Neurosci 1990;13 (7) 296- 302
PubMed Link to Article
Hutton  JTMorris  JLElias  JW Levodopa improves spatial contrast sensitivity in Parkinson's disease. Arch Neurol 1993;50721- 724
Link to Article
Maffei  LFiorentini  ABisti  SHolländer  H Pattern ERG in the monkey after section of the optic nerve. Exp Brain Res 1985;59 (2) 423- 425
PubMed Link to Article
Bobak  PBodis-Wollner  IHarnois  C  et al.  Pattern electroretinograms and visual-evoked potentials in glaucoma and multiple sclerosis. Am J Ophthalmol 1983;96 (1) 72- 83
PubMed
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