In this study, we used SS-OCT to investigate the effects of autonomic dysfunction and neurodegeneration in PD on the retina and choroid. Our results revealed that the GCL + IPL and CT were thinner, and C, L, and I were decreased in patients with PD compared to those without PD. A 3-year follow-up of patients with PD revealed a decreased RNFL thickness and I.
The source of retinal thinning may be related to neurodegeneration associated with the pathology of PD. The appearance of Lewy bodies, which contain abnormal deposition of amyloid fibrils, can be observed in the nerve cells of patients with PD. Such amyloidosis also occurs in the GCL of ocular tissues and may cause nerve degeneration in the retina . Furthermore, retinal dopaminergic neurons are present in amacrine cells, and the IPL corresponds to the dendrites of amacrine cells. It has been reported that visual pathologies in patients with PD may be caused by dopamine reduction in retinal amacrine cells [13, 14]. The concentration of retinal dopaminergic neurons in patients with PD has been shown to be lower than that in healthy individuals . The reduction in dopamine caused by PD results in the thinning of the IPL due to a deficit in retinal dopaminergic neurons [3, 16]. Therefore, PD-induced neurodegeneration may be associated with GCL and IPL thinning in the macular region, as observed in this study.
Contrastingly, the RNFL thickness in patients with PD was not significantly different from that in patients without PD in this study. Kirbas et al.  and Turgay et al.  reported that the RNFL and GCL + IPL were thinner around the optic disc in patients with PD than in healthy controls. In this study, the RNFL of the macular region was considered; the discrepancy between our findings and theirs suggests that to investigate minor changes in RNFL thickness, analysis of the region surrounding the optic disc may be more appropriate. However, Altıntaş et al.  reported that the RNFL thickness was decreased in patients with PD than in healthy controls. In our study, macular analysis showed that the retinas of patients with PD were significantly thinner after 3 years compared to the first visit. Atum et al.  followed-up the retina in the macular analysis of patients with PD for 2 years. As a result, a thinner RNFL thickness was reported in patients with PD than in healthy controls. Therefore, it may be useful to combine macular and optic disc analyses for the analysis of the retina of patients with PD. Similarly, glaucoma is an eye disease that causes thinning of the RNFL and GCL + IPL. Patients with PD have been shown to have a high prevalence of glaucoma , and measurement of the retina using OCT may be important for both observations.
In this study, the choroid was thinner in patients with PD compared to patients without PD; thinning of the choroid was observed as C decreased, and both L and I decreased concomitantly. We suspect that there was no significant difference in L/C because C decreased while the relative proportions of L and I remained constant. It has been reported that the CT in patients with PD is less than that of healthy individuals, which is consistent with the current findings [20, 21]. We performed binarization to investigate the cause of the choroid thinning. Few reports have examined the choroid of patients with PD using this method.
Considering that choroidal thinning is caused by a reduction in L, the reduced blood flow may be the result of autonomic dysfunction in PD. The smooth muscle of the choroidal vascular wall contains autonomic innervation, which is associated with changes in ocular blood flow . Choroidal blood flow exhibits a circadian rhythm ; thus, autonomic dysfunction in PD may affect choroidal blood flow. Therefore, the reduction in L observed in this study may be due to the reduced blood flow associated with chronic circulatory disturbances caused by autonomic dysfunction in PD.
The decrease in I may be induced by changes in the number of melanocytes in the interstitial region. In the pathology of PD, the black tone of the substantia nigra is reduced due to the loss of cells with melanin. Melanocytes are produced when tyrosine (a precursor of dopamine) is exposed to ultraviolet light and then activated by tyrosinase. Tyrosine is a precursor of the neurotransmitter dopamine. In PD, where dopamine is selectively impaired, tyrosinase activity and melanocyte production may be concomitantly reduced. Changes in the choroid of patients with PD may progress more rapidly than changes in the choroid of patients of the same age without PD, and the degeneration of melanocytes may be involved in the thinning of the choroid. Additionally, the choroid of patients with PD after 3 years showed a decrease in I only compared to the first visit. Thus, the observation of I in the choroid may be useful for monitoring PD.
In this study, we investigated the follow-up of the retina and choroid in patients with PD. We hypothesized that the duration of PD would reduce the thickness of the retina and choroid. However, the results obtained from seven patients with PD indicate that the length of the disease duration period is not necessarily the factor that reduces the thickness of the retina and choroid. This result indicates that the length of the disease duration of PD may not be correlated with the amount of decrease in the choroid.
This study has several limitations. Although significant differences in the retina and choroid were observed, the number of participants was too small to allow us to draw definitive conclusions. Additionally, the retina was evaluated in the macula, and the choroid was evaluated only in the subfoveal tomographic image. Therefore, it may be different from the evaluation of the entire eye. Moreover, the correlation of the retina and choroid between severity classifications from Hoehn and Yahr could not be investigated. Sari et al.  reported that the retinal thickness was correlated with the severity classification of Hoehn and Yahr. Contrastingly, Eraslan et al.  reported that the retinal thickness was decreased but did not coincide with the severity classification for Hoehn and Yahr. In this study, the severity of all patients was stage III at the first visit. After 3 years, two subjects had stage IV severity, but more cases need to be considered. In this study, choroidal binarization reduced I in patients with PD, and we focused on melanocytes. However, there are various cells other than melanocytes in the interstitial region, which is why we cannot exclude the possibility of other influencing factors on the current results; therefore, more studies and histological analyses are required to corroborate our findings. Moreover, the changes in the retina and choroid of patients with PD after 3 years were discussed considering the length of the disease period; however, to clarify this, it is necessary to conduct a comparative study in groups divided by the disease duration.
Evaluation of the retina and choroid using SS-OCT may serve as a biomarker for the assessment of central nervous degenerative diseases [24, 25]. The current findings suggest that autonomic dysfunction and neurodegeneration in PD result in structural changes in the retina and choroid.