L E T T E R S :
P U B L I S H E D
A R T I C L E S
with ET, representing a frequency of 24%. When we restrict the analysis to those who come into the program as controls and receive a research diagnosis of ET, that frequency is 5% (27/531) This is in keeping with other studies in which elderly individuals are carefully examined by a movement specialist.2 In the last 2 years, we have begun actively recruiting for subjects with longstanding ET, so we would expect these numbers to continue to increase. We acknowledge that the disease duration is short but, as pointed out in the consensus statement, this does not affect whether a subject meets criteria for a diagnosis of ET. We did address the issue by separating out the 25 individuals with longer-duration, clinically diagnosed ET and found a nonsignificant increase in Purkinje cell count. The issues of the Canadian group’s results and alcohol intake have been addressed significantly in our paper and in the literature and will not be commented on further. We do not argue that Purkinje cells might not be disrupted; only that it does not appear to be a primary issue in ET, as has been suggested in recent editorials,3 and that we still have not yet identified the primary abnormality. We appreciate that this seems to be coming out more clearly in recent papers by the Columbia group. Holly A. Shill,*1,2 Charles H. Adler,3 and Joseph G. Hentz3 1 Banner Sun Health Research Institute, Sun City, Arizona, USA 2 University of Arizona College of Medicine, Phoenix, Arizona, USA 3 Mayo Clinic Arizona, Scottsdale, Arizona, USA
References 1.
Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord. 1998;13(Suppl 3).
2.
Elble RJ. Tremor in ostensibly normal elderly people. Mov Disord 1998;13:457-464.
3.
Grimaldi G, Manto M. Is essential tremor a Purkinjopathy? The role of the cerebellar cortex in its pathogenesis. Mov Disord 2013; 28:1759-1761.
Photoreceptor Layer Thinning is Not Specific for Parkinson’s Disease Dear Editor, I read with interest the paper by Roth et al. entitled “Photoreceptor thinning in idiopathic Parkinson’s disease.”1
------------------------------------------------------------
*Correspondence to: Dr. Thomas Theelen, RadboudUMC, Ophthalmology, Philips van Leydenlaan 15, Nijmegen, Netherlands, 6525 EX, E-mail: [email protected] Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Received: 9 May 2014; Accepted: 2 June 2014 Published online 28 June 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.25949
FIG. 1. Illustration of photoreceptor thinning by primarily ophthalmological diseases. From top: age related macular degeneration, macular dystrophy, and high myopia.
The authors performed automated layer thickness measurements on optical coherence tomography (OCT) of healthy controls (HC) and eyes of patients with Parkinson’s disease (PD). Their results contradict recent similar studies that found either no differences between HC and PD or thinning in the inner retina and not in the photoreceptor layer.2 The interpretation of any results of macular OCT scan measurements typically requires thorough knowledge of macular pathology. Particularly, several common ophthalmological diseases such as macular degeneration may significantly decrease photoreceptor layer thickness on OCT,3 which is illustrated in Figure 1 by three examples of well-known ophthalmological diseases causing photoreceptor thinning. Conversely, Roth et al. did not perform ophthalmological examinations of their patients, and retinal specialists were apparently not involved in the interpretation of the OCT scans to ensure that the study results were not confused with primarily retinal pathological conditions.1 Hence, an interdisciplinary approach between neurologists and ophthalmologists should be considered in OCT studies on retinal changes in neurological disorders such as PD or multiple sclerosis. The significance of any results could then be increased by avoiding the risk of overlooking important, primarily retinal disorders.
Movement Disorders, Vol. 29, No. 10, 2014
1331
L E T T E R S :
1
P U B L I S H E D
A R T I C L E S
Thomas Theelen, MD, PhD1 RadboudUMC, Ophthalmology, Nijmegen, The Netherlands
References 1.
Roth NM, Saidha S, Zimmermann H, et al. Photoreceptor layer thinning in idiopathic Parkinson’s disease. Mov Disord 2014.
2.
Lee JY, Ahn J, Kim TW, Jeon BS. Optical coherence tomography in Parkinson’s disease: is the retina a biomarker? J Parkinson Dis 2014.
3.
Schuman SG, Koreishi AF, Farsiu S, Jung SH, Izatt JA, Toth CA. Photoreceptor layer thinning over drusen in eyes with agerelated macular degeneration imaged in vivo with spectraldomain optical coherence tomography. Ophthalmology 2009; 116:488-496.
Reply: Photoreceptor Layer Thinning Is Not Specific for Parkinson’s Disease Reply letter Dear Editor We wish to thank Dr. Theelen for his letter regarding our recent paper on photoreceptor layer thinning in Parkinson’s disease (PD).1 We agree that the investigation of retinal pathological conditions in PD, and other neurological disorders, both within the scope of clinical care and research, should be a concerted and collaborative approach by ophthalmologists and neurologists. Given the comparably older age of PD patients, primary ophthalmologic disorders may be more common in such patients, although their detection may be somewhat hampered by the disability and immobility commonly seen in PD. Although primary retinal disorders are more common in the elderly, the overall prevalence of conditions such as age-related macular degeneration and macular dystrophy remains low. Therefore, from a statistical perspective, average thickness of the photoreceptor layer in a cohort of PD patients would be unlikely to be significantly reduced relative to controls, unless most of the included PD patients were afflicted by co-incidental and previously undetected concomitant retinal diseases. This of course is most unlikely. Moreover, our collective group is highly experienced in the investigation and interpretation of optical coherence tomography scans, from both quantitative and qualitative perspectives, and would be most unlikely to overlook such obvious retinal pathological conditions as those illustrated by Dr. Theelen. All optical coherence tomography scans were carefully examined to exclude any confounding measurements that
------------------------------------------------------------
*Correspondence to: Alexander U. Brandt, NeuroCure Clinical Research - Universita €tsmedizin Berlin, Germany, E-mail: Center, Charite [email protected] Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Received: 27 May 2014; Accepted: 2 June 2014 Published online 1 July 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.25957
1332
Movement Disorders, Vol. 29, No. 10, 2014
could be construed for PD-unrelated retinal pathological conditions. This led to the exclusion of a large number of scans. Nonetheless, the possibility that our results may be confounded to a degree by ophthalmologic disorders is acknowledged and discussed as a potential weakness in our original publication. Because we did not detect significant retinal nerve fiber layer (RNFL) thinning in this cohort of PD patients, as has been previously described in glaucoma2 as well as in PD itself,3 a glaucomatous confound is as unlikely as that from primarily retinal disorders. To clarify, our study findings do not contradict those of previous studies with regard to photoreceptor changes in PD. This is the first study to investigate the photoreceptor layer in PD using a reliable method.4 In fact, an immediate reply to our paper by an independent group further supports our findings, making it unlikely that our findings are either coincidental or attributable to a PD-unrelated process.5 Our study’s results do contradict previous studies with regard to RNFL thinning, which others found3 and we did not.1 This discrepancy and its potential causes were discussed in detail in our main publication and the reply to M€ uller et al.1,5 Please refer to these for further detail. We were not implying that photoreceptor thinning is by any means specific to PD. Important ophthalmological diseases, such as age-related macular degeneration, may produce photoreceptor loss. Naturally, these diseases should be diagnosed and treated by an ophthalmologist. However, amongst neurological diseases, and especially neurodegenerative diseases, photoreceptor layer thinning has rarely been reported, with RNFL thinning representing the most frequently reported finding. For the neurologist, therefore, investigating the photoreceptor in PD, after ruling out potential unrelated retinal or macular diseases in collaboration with an ophthalmologist, might prove to be a potentially important addition in primary or secondary diagnostics. Alexander U. Brandt, MD,1 Peter A. Calabresi, MD2, and Shiv Saidha, MD2 1 NeuroCure Clinical Research Center, Charite Universit€atsmedizin Berlin, Germany 2 Department of Neurology, Johns Hopkins School of Medicine, Baltimore, USA
References 1.
Roth NM, Saidha S, Zimmermann H, et al. Photoreceptor layer thinning in idiopathic Parkinson’s disease. Mov Disord 2014; [Epub ahead of print]
2.
Bock M, Brandt AU, D€ orr J, et al. Patterns of retinal nerve fiber layer loss in multiple sclerosis patients with or without optic neuritis and glaucoma patients. Clin Neurol Neurosurg 2010;112:647652.
3.
Yu J-G, Feng Y-F, Xiang Y, et al. Retinal nerve fiber layer thickness changes in Parkinson disease: a meta-analysis. PLoS ONE 2014;9:e85718.
4.
Seigo MA, Sotirchos ES, Newsome S, et al. In vivo assessment of retinal neuronal layers in multiple sclerosis with manual and automated optical coherence tomography segmentation techniques. J Neurol 2012;259:2119-2130.
5.
M€ uller A-K, Blasberg C, S€ udmeyer M, et al. Photoreceptor layer thinning in parkinsonian syndromes. Mov Dis 2014; [Epub ahead of print]
P U B L I S H E D
A R T I C L E S
with ET, representing a frequency of 24%. When we restrict the analysis to those who come into the program as controls and receive a research diagnosis of ET, that frequency is 5% (27/531) This is in keeping with other studies in which elderly individuals are carefully examined by a movement specialist.2 In the last 2 years, we have begun actively recruiting for subjects with longstanding ET, so we would expect these numbers to continue to increase. We acknowledge that the disease duration is short but, as pointed out in the consensus statement, this does not affect whether a subject meets criteria for a diagnosis of ET. We did address the issue by separating out the 25 individuals with longer-duration, clinically diagnosed ET and found a nonsignificant increase in Purkinje cell count. The issues of the Canadian group’s results and alcohol intake have been addressed significantly in our paper and in the literature and will not be commented on further. We do not argue that Purkinje cells might not be disrupted; only that it does not appear to be a primary issue in ET, as has been suggested in recent editorials,3 and that we still have not yet identified the primary abnormality. We appreciate that this seems to be coming out more clearly in recent papers by the Columbia group. Holly A. Shill,*1,2 Charles H. Adler,3 and Joseph G. Hentz3 1 Banner Sun Health Research Institute, Sun City, Arizona, USA 2 University of Arizona College of Medicine, Phoenix, Arizona, USA 3 Mayo Clinic Arizona, Scottsdale, Arizona, USA
References 1.
Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord. 1998;13(Suppl 3).
2.
Elble RJ. Tremor in ostensibly normal elderly people. Mov Disord 1998;13:457-464.
3.
Grimaldi G, Manto M. Is essential tremor a Purkinjopathy? The role of the cerebellar cortex in its pathogenesis. Mov Disord 2013; 28:1759-1761.
Photoreceptor Layer Thinning is Not Specific for Parkinson’s Disease Dear Editor, I read with interest the paper by Roth et al. entitled “Photoreceptor thinning in idiopathic Parkinson’s disease.”1
------------------------------------------------------------
*Correspondence to: Dr. Thomas Theelen, RadboudUMC, Ophthalmology, Philips van Leydenlaan 15, Nijmegen, Netherlands, 6525 EX, E-mail: [email protected] Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Received: 9 May 2014; Accepted: 2 June 2014 Published online 28 June 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.25949
FIG. 1. Illustration of photoreceptor thinning by primarily ophthalmological diseases. From top: age related macular degeneration, macular dystrophy, and high myopia.
The authors performed automated layer thickness measurements on optical coherence tomography (OCT) of healthy controls (HC) and eyes of patients with Parkinson’s disease (PD). Their results contradict recent similar studies that found either no differences between HC and PD or thinning in the inner retina and not in the photoreceptor layer.2 The interpretation of any results of macular OCT scan measurements typically requires thorough knowledge of macular pathology. Particularly, several common ophthalmological diseases such as macular degeneration may significantly decrease photoreceptor layer thickness on OCT,3 which is illustrated in Figure 1 by three examples of well-known ophthalmological diseases causing photoreceptor thinning. Conversely, Roth et al. did not perform ophthalmological examinations of their patients, and retinal specialists were apparently not involved in the interpretation of the OCT scans to ensure that the study results were not confused with primarily retinal pathological conditions.1 Hence, an interdisciplinary approach between neurologists and ophthalmologists should be considered in OCT studies on retinal changes in neurological disorders such as PD or multiple sclerosis. The significance of any results could then be increased by avoiding the risk of overlooking important, primarily retinal disorders.
Movement Disorders, Vol. 29, No. 10, 2014
1331
L E T T E R S :
1
P U B L I S H E D
A R T I C L E S
Thomas Theelen, MD, PhD1 RadboudUMC, Ophthalmology, Nijmegen, The Netherlands
References 1.
Roth NM, Saidha S, Zimmermann H, et al. Photoreceptor layer thinning in idiopathic Parkinson’s disease. Mov Disord 2014.
2.
Lee JY, Ahn J, Kim TW, Jeon BS. Optical coherence tomography in Parkinson’s disease: is the retina a biomarker? J Parkinson Dis 2014.
3.
Schuman SG, Koreishi AF, Farsiu S, Jung SH, Izatt JA, Toth CA. Photoreceptor layer thinning over drusen in eyes with agerelated macular degeneration imaged in vivo with spectraldomain optical coherence tomography. Ophthalmology 2009; 116:488-496.
Reply: Photoreceptor Layer Thinning Is Not Specific for Parkinson’s Disease Reply letter Dear Editor We wish to thank Dr. Theelen for his letter regarding our recent paper on photoreceptor layer thinning in Parkinson’s disease (PD).1 We agree that the investigation of retinal pathological conditions in PD, and other neurological disorders, both within the scope of clinical care and research, should be a concerted and collaborative approach by ophthalmologists and neurologists. Given the comparably older age of PD patients, primary ophthalmologic disorders may be more common in such patients, although their detection may be somewhat hampered by the disability and immobility commonly seen in PD. Although primary retinal disorders are more common in the elderly, the overall prevalence of conditions such as age-related macular degeneration and macular dystrophy remains low. Therefore, from a statistical perspective, average thickness of the photoreceptor layer in a cohort of PD patients would be unlikely to be significantly reduced relative to controls, unless most of the included PD patients were afflicted by co-incidental and previously undetected concomitant retinal diseases. This of course is most unlikely. Moreover, our collective group is highly experienced in the investigation and interpretation of optical coherence tomography scans, from both quantitative and qualitative perspectives, and would be most unlikely to overlook such obvious retinal pathological conditions as those illustrated by Dr. Theelen. All optical coherence tomography scans were carefully examined to exclude any confounding measurements that
------------------------------------------------------------
*Correspondence to: Alexander U. Brandt, NeuroCure Clinical Research - Universita €tsmedizin Berlin, Germany, E-mail: Center, Charite [email protected] Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article. Received: 27 May 2014; Accepted: 2 June 2014 Published online 1 July 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.25957
1332
Movement Disorders, Vol. 29, No. 10, 2014
could be construed for PD-unrelated retinal pathological conditions. This led to the exclusion of a large number of scans. Nonetheless, the possibility that our results may be confounded to a degree by ophthalmologic disorders is acknowledged and discussed as a potential weakness in our original publication. Because we did not detect significant retinal nerve fiber layer (RNFL) thinning in this cohort of PD patients, as has been previously described in glaucoma2 as well as in PD itself,3 a glaucomatous confound is as unlikely as that from primarily retinal disorders. To clarify, our study findings do not contradict those of previous studies with regard to photoreceptor changes in PD. This is the first study to investigate the photoreceptor layer in PD using a reliable method.4 In fact, an immediate reply to our paper by an independent group further supports our findings, making it unlikely that our findings are either coincidental or attributable to a PD-unrelated process.5 Our study’s results do contradict previous studies with regard to RNFL thinning, which others found3 and we did not.1 This discrepancy and its potential causes were discussed in detail in our main publication and the reply to M€ uller et al.1,5 Please refer to these for further detail. We were not implying that photoreceptor thinning is by any means specific to PD. Important ophthalmological diseases, such as age-related macular degeneration, may produce photoreceptor loss. Naturally, these diseases should be diagnosed and treated by an ophthalmologist. However, amongst neurological diseases, and especially neurodegenerative diseases, photoreceptor layer thinning has rarely been reported, with RNFL thinning representing the most frequently reported finding. For the neurologist, therefore, investigating the photoreceptor in PD, after ruling out potential unrelated retinal or macular diseases in collaboration with an ophthalmologist, might prove to be a potentially important addition in primary or secondary diagnostics. Alexander U. Brandt, MD,1 Peter A. Calabresi, MD2, and Shiv Saidha, MD2 1 NeuroCure Clinical Research Center, Charite Universit€atsmedizin Berlin, Germany 2 Department of Neurology, Johns Hopkins School of Medicine, Baltimore, USA
References 1.
Roth NM, Saidha S, Zimmermann H, et al. Photoreceptor layer thinning in idiopathic Parkinson’s disease. Mov Disord 2014; [Epub ahead of print]
2.
Bock M, Brandt AU, D€ orr J, et al. Patterns of retinal nerve fiber layer loss in multiple sclerosis patients with or without optic neuritis and glaucoma patients. Clin Neurol Neurosurg 2010;112:647652.
3.
Yu J-G, Feng Y-F, Xiang Y, et al. Retinal nerve fiber layer thickness changes in Parkinson disease: a meta-analysis. PLoS ONE 2014;9:e85718.
4.
Seigo MA, Sotirchos ES, Newsome S, et al. In vivo assessment of retinal neuronal layers in multiple sclerosis with manual and automated optical coherence tomography segmentation techniques. J Neurol 2012;259:2119-2130.
5.
M€ uller A-K, Blasberg C, S€ udmeyer M, et al. Photoreceptor layer thinning in parkinsonian syndromes. Mov Dis 2014; [Epub ahead of print]
