Independent patterns of damage within magno-, parvo- and koniocellular pathways in Parkinson's disease (Silva MF et al. Brain 2005; 128: 2260–2271)
Correspondence to: Gaynes Bruce, 1725 W. Harrison Street, Suite 931, Chicago, IL 60612, USA E-mail: bgaynes{at}rush.edu
Received May 31, 2006. Revised August 2, 2006. Accepted September 11, 2006.
I have read with interest the recent article on loss of visual function associated with Parkinson's disease by Silva et al. (2005)
. The authors conclude that achromatic and chromatic deficits among Parkinson's disease subjects, as measured psychophysically, occur in an ‘independent’ fashion with potential confounding features due to age Silva et al. (2005).
However, while the general premise of the study methodology appears valid, it is unclear how conclusions regarding confounding effects of age as well as the ‘independent’ patterns of Parkinson's disease related pathophysiology can be ascertained accurately solely within the context of a cross-sectional psychophysical assessment of visual function. What the study does clearly identify are distinct patterns of visual deficit among groups of Parkinson's disease subjects with various levels of disease involvement as well as ‘normal’ controls among individuals with an approximate age of 60 years. Conclusions as to whether or not Parkinson's disease related visual deficits are the result of independent ‘damage’ to visual pathways, or are confounded by age, simply cannot be determined by an otherwise isolated demonstration of psychometric circumstance via the context of an age-matched case–control study.
Parkinson's disease related influences on visual function are likely not only dynamic in nature, but differentially affected based on the course of the disease and, perhaps more importantly, its treatment (Inzelberg et al., 2004). Comparative assessment of the pathophysiologic ‘independence’ of Parkinson's disease visual correlates would intuitively require more than static measures of psychophysical function due not only to physiologic differences in the sensitivity, selectivity and distribution of dopamine receptors within the retina, but due to the pleiotropic and redundant nature of ganglion cell receptive field properties (Rodieck, 1998). Alteration in cellular and dopaminergic synaptic function as a result of Parkinson's disease related dopamine deficit is believed to result in modification of visual processing due to alteration of ganglion cell receptive field properties as well as amacrine and horizontal cell networks that contribute to both spatial resolution as well as chromaticity (Djamgoz et al., 1997). Moreover, dopamine receptor subtypes found in the brain as well as retina demonstrate differential susceptibility not only to the effect of experimental parkinsonism and dopaminergic denervation, but in response to dopaminergic agonist therapy as well, possibly related to the presence of presynaptic autoreceptors (Graham et al., 1990, 1993; Nowak et al., 1991; Yazulla and Lin, 1995). It is noteworthy that modification of receptor sensitivity following dopaminergic drug therapy subsequent to experimental parkinsonism has been implicated in the development of dopaminergic drug-related dyskinesia and indeed may be related to visual abnormalities as well (Graham et al., 1993). Therefore, determination of independent damage to visual pathways subsequent to Parkinson's disease by a single psychophysical measurement would certainly appear to oversimplify Parkinson's disease related perturbation in retinal function that are likely temporally related, receptor defined and perhaps better described as mutually interdependent, rather than exclusively independent, as psychophysical analysis would predictably suggest.
Moreover, the confounding effects of dopaminergic pharmacotherapy on retinal function may in fact be masked by potential dopaminergic neurotoxicity previously linked with levodopa administration both clinically as well as experimentally (Asanuma et al., 2003; Fahn et al., 2004). Unfortunately, because the authors stratified subjects based on disease category rather than drug history and evaluated subjects by cross-sectional analysis, any appraisal of the post hoc relationship between drug therapy and visual abnormalities is, at best, presumptuous.
Curiously, the finding of red–green chromatic defects in Parkinson's disease patients by Silva et al. (2005) is incongruent with previous psychophysical and electroretinographic data suggesting that Parkinson's disease patients demonstrate consistent and predominant blue–yellow cone deficiencies, which, interestingly, has been exploited as a novel means to detect early glaucomatous visual field changes (Johnson et al., 1993; Haug et al., 1995; Djamgoz et al., 1997; Sartucci et al., 2003; Inzelberg et al., 2004). Indeed, previous studies have appropriately shown that Parkinson's disease patients demonstrate frank thinning of retinal ganglion cell axons reminiscent of ocular neurodegenerative diseases, such as glaucoma, where ganglion cell loss comprises an important part of disease pathophysiology and concomitant magno-, konio- and parvocellular deficits coexist (Johnson and Samuels, 1997; Yucel et al., 2003; Inzelberg et al., 2004). Although the methodology of Silva et al. (2005) suggests a predominant red–green abnormality among Parkinson's disease subjects, relevance as to the relationship between ganglion cell loss and its importance to chromatic sensitivity is obfuscated.
Although Silva et al. (2005) suggest that progressive Parkinson's disease appears to be related to decline in achromatic dynamic contrast sensitivity, readers lack key information regarding the specific breakdown of the number of subjects in each UPDRS disease category described. Lacking knowledge of the number of patients in each category certainly reduces the validity of any conclusion regarding progression of dynamic contrast deficit as well as the association between loss of chromaticity and disease progression. Furthermore, without a well defined explanation of the type of sampling the authors employed in order to fulfil recruitment, such as population based, purposive or convenience, the external validity of the study results are uncertain. In summary, the study design and underlying assumption regarding Parkinson's disease related disturbances in retinal neurobiology and resultant hierarchical consequences in visual function contribute to a verisimilitude of findings that, unfortunately, obscure any meaningful conclusion regarding autonomous injury to visual pathways as a result of Parkinson's disease.
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