The present study did not provide evidence of RNFL thinning in patients with PD. However, VF defects were more frequent in PD patients compared to controls.
A number of previous studies [10
], although not all [14
], provided evidence of reduced RNFL thickness in PD patients. Inzelberg et al. [11
] reported a reduction in the infero temporal RNFL thickness, which was topographically matched to the VF defects, in a subset of five patients with reliable VFs. A reduction in average RNFL thickness, macular thickness and volume was also reported in another study in PD patients [11
]. Decreased RNFL thickness has also been suggested in PD patients examined with scanning laser ophthalmoscopy [21
]. Moschos et al. [12
] reported reduced temporal and inferior RNFL thickness in PD patients compared to controls. However, in agreement with our results, mean RNFL thickness did not differ between the groups. In addition, OCT findings with spectral domain OCT (SD-OCT) suggest a decreased thickness of the paramacular inner retina, including the nerve fiber layer, the ganglion cell layer and the inner plexiform layer in PD patients, while outer retinal layer thickness was not found to differ from controls [22
]. Increased inner nuclear layer thickness has been identified in a more recent study [16
The finding of RNFL thinning in PD patients has been attributed to the loss of trophic effects induced by dopamine depletion in the retina [7
]. Although autopsy studies have documented decreased retinal dopamine concentration in PD patients [9
], degeneration of retinal dopaminergic neurons and changes in cell density have not been shown [8
]. It is not obvious how dopamine depletion could mediate RNFL thinning in PD. A pilot study using the recently introduced SD-OCT imaging platform did not detect differences in the RNFL thickness of PD patients and controls [14
]. Moreover, Archibald et al. failed to detect any RNFL thinning in PD patients, but showed more frequent functional visual defects [15
]. In another study in PD patients, no evidence of RNFL thinning with the use of SD- OCT was found [16
]. Similarly, in our present study, no significant difference was detected in RNFL thickness in PD patients and controls. Discrepancies between studies may be attributed to differences in study populations, small sample size in some reports, different stages of disease and differences in imaging technologies. In our study, the widely available time-domain OCT platform (Stratus OCT) was used. This device is based on low-coherence interferometry to produce high-resolution, two-dimensional images of the optic nerve head and retina [23
]. More recently, SD-OCT, with a scanning speed up to 200 times higher than time-domain OCT and a higher axial resolution was introduced in clinical practice [24
]. Consequently, it could be argued that SD-OCT would provide more valid data and a greater discriminating ability than time-domain OCT. However, despite the theoretical advantages of the superior reproducibility, resolution and higher scanning speed, recent studies have failed to demonstrate an unequivocal superiority of the commercially available SD-OCT devices over time-domain OCT in the assessment of optic nerve diseases [27
]. Therefore, the use of the widely available Stratus OCT that employs time-domain technology instead of newer SD-OCT devices may not necessarily limit the validity of our results.
Compared to structural tests, visual function tests may be more relevant in detecting differences between PD patients and controls. Yenice et al. [17
] studied VFs in 14 patients with PD, and found decreased MD and PSD scores compared to the control group. In that study, six eyes had nasal steps and six eyes had arcuate defects. A pattern that resembles nerve fiber bundle defects and glaucomatous-like VF loss was also observed in PD patients in our study: 73% of 48 eyes had a GHT outside normal limits, compared to 50% of 28 eyes in the study by Yenice et al. It should be noted that the GHT is an algorithm that was specifically developed for glaucoma. However, we have chosen to analyze GHT results due to the resemblance of typical glaucomatous VF defects with the scotomas found in our non-glaucoma cohort of PD patients. In line with the report by Yenice et al. [17
], arcuate defects, nasal steps and paracentral scotomas were also found in our patients. Bilateral VF damage was identified in 14 of our patients.
An increased occurrence of probable glaucoma was reported in a retrospective chart review of 38 patients with PD [30
]. To ensure that our participants did not have glaucoma, that could confound our results, we excluded PD patients and controls who had positive family history of glaucoma, narrow anterior chamber angles on gonioscopy or optic disc findings suspicious for glaucoma. Therefore, despite the similarities of glaucomatous scotomas with the scotomas detected in our study, it is quite unlikely that the perimetric findings observed in our patients can be attributed to glaucomatous neuropathy. In glaucoma, there is typically a matching of structural and functional damage. Characteristic VF defects in glaucoma patients can usually be matched to topographically corresponding damage of the optic disc and/or RNFL. The glaucomatous-like visual field defects observed in our series of non-glaucoma PD patients, however, could not be matched to corresponding RNFL thinning (Figure
). Instead, it is reasonable to assume that the functional deficit observed in this cohort of patients can be explained by intra-retinal, subcortical and cortical neuronal disorganization or injury related to PD.
Animal and human studies have suggested the involvement of the visual pathway in the disease process of PD [31
]. It was shown that higher cortical visual processes, as well as the retina may be affected [6
]. Reduced responses have been reported by means of pattern electroretinograms (pERG) reflecting ganglion cell dysfunction [33
], as well as flash ERG, indicating outer retina impairment [34
]. Multifocal ERG testing, which is believed to mainly reflect bipolar cell activity also revealed differences in PD patients and controls [12
]. pERG studies also highlighted changes in retinal ganglion cell function in PD [34
]. Increased latencies in visual evoked potentials (VEP) were also found, corresponding to a delayed response to visual stimuli due to retinal or post-retinal processing dysfunction [34
]. This delayed response could at least in part originate from retinal damage, given that dopamine neurons are rare in the visual system at sites other than the retina [5
Indeed, the pathophysiological basis of the functional visual system impairment in PD has not been fully elucidated. A decrease in dopamine concentration has been found in the retina of patients suffering from PD [9
]. Although the role of dopamine in the retinal neural circuitry is not fully understood, there is evidence that dopaminergic deficiency may directly or indirectly affect amacrine, horizontal and retinal ganglion cells and modify the receptive field output of the retina [6
]. These changes in the coupling between the different cellular systems that form the retinal network could, at least in part, explain the VF defects observed in the present study.
L-dopa therapy in PD patients may also have an effect on visual parameters. Actually, administration of L-dopa in PD patients was found to transiently reverse contrast sensitivity abnormalities, pERG alterations and VEP latencies [6
]. On the contrary, in our sample, VF defects were identified despite our patients being under optimal L-Dopa treatment and in “ON” period. This suggests that apart from dopamine deficiency, there may also be additional mechanisms accounting for retinal dysfunction in patients with PD.
It should be noted that fixation problems and motor system symptoms can also make VF testing a demanding task for this group of patients. Moreover, it has been shown that reaction times and saccadic eye movements may be affected in PD [38
], leading to poor VF performance. However, all patients analyzed in the present study had reliable VFs. Additionally, the 24–2 SITA-Standard algorithm that was used offers the advantage of a relatively short testing time compared to other full-threshold strategies [39
]. Another relevant feature of this algorithm is that it continuously monitors the patient’s response rate and adjusts the stimulus presentation rate accordingly [40
]. Therefore, motor dysfunction per se
cannot fully explain the worse perimetric performance of our patients compared to age-matched controls. In addition, visuo-spatial deficits and dysfunction of the visual information processing from the retina to the visual cortex was also reported in PD patients [6
] and could contribute to VF defects. However, in the present study, PD patients had a mean MMSE score that corresponds to a normal cognitive function, while 6 patients had a score under the recently suggested cut-off value [41
]. Analysis of the data did not show any correlation between the MMSE score and VF indices. This finding may suggest that VF damage in PD patients can be attributed, at least to a certain extent, to retinal dysfunction.
Regardless of the underlying pathophysiological mechanism, our finding that PD patients can have significant visual field defects is clinically relevant. Clinicians need to be aware of the association between this neurodegenerative disorder and visual field deficits. In fact, the attribution of “true” glaucomatous VF defects in PD patients with definite glaucoma can be clinically challenging. In such cases, as previously discussed, careful attention to the matching patterns of structural and functional damage would be critical for the assessment of possible glaucomatous damage. Even more, as judged by the depth and extent of the scotomas, an appreciable functional deficit could be anticipated for at least some of these patients. The impact of these VF defects on the patient’s quality of life remains to be determined.