Does choroidal thickness change in Parkinson’s dis­ease?


Mění se při Parkinsonově nemoci tloušťka cévnatky?

Cíl: Stanovit tloušťku cévnatky u pa­cientů s Parkinsonovou nemocí (PN) v porovnání se zdravými jedinci a vyhodnotit vztah mezi trváním onemocnění a tloušťkou cévnatky.

Materiály a metody: Studovaná skupina zahrnula 24 pravých očí 24 pa­cientů s PN a kontrolní skupina zahrnula 25 pravých očí 25 zdravých jedinců. Tloušťka cévnatky byla v obou skupinách měřena optickou koherentní tomografií ve spektrální doméně (SD-OCT) v 6 bodech: ve středu fovea centralis a 500µm intervalech temporálně (3 body) a nazálně (2 body) od středu fovea centralis. Skupiny byly porovnány podle hodnot tloušťky cévnatky a byly provedeny skupinové analýzy. Dále byla hodnocena korelace mezi trváním PN a tloušťkou cévnatky.

Výsledky: Střední věk 24 pa­cientů s PN (14 mužů) byl 67,5 ± 12,8 let a průměrný věk 25 zdravých jedinců (13 mužů) byl 66,1 ± 9,7 let. Mezi skupinami nebyly s ohledem na věk nebo pohlaví žádné významné rozdíly (p = 0,59 a p = 0,768). U pa­cientů s PN byly pozorovány významně vyšší hodnoty tloušťky cévnatky subfoveálně (p = 0,04), 500 µm nazálně (p = 0,03) a 500, 1 000 a 1 500 µm temporálně od středu fovea centralis (p = 0,02, p = 0,02, resp. p = 0,02, ). Mezi trváním PN a tloušťkou cévnatky nebyla shledána žádná korelace (p > 0,05).

Závěr: Tloušťka cévnatky může být u pa­cientů s PN vyšší v porovnání se zdravými jedinci. Pro potvrzení našich výsledků a zhodnocení souvisejících patofyziologických mechanismů jsou však zapotřebí další studie.

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Klíčová slova:

tloušťka cévnatky – optická koherentní tomografie


Authors: Ç. Öktem 1;  E. Ö. Öktem 2;  A. Kurt 1;  R. Kilic 3
Authors‘ workplace: Department of Ophthalmology, Alaaddin Keykubat University Alanya Education and Research Hospital, Antalya, Turkey 1;  Department of Neurology, Alaaddin Keykubat University Alanya Education and Research Hospital, Antalya, Turkey 2;  Department of Ophthalmology, Ahi Evran University Education and Research Hospital Kirsehir, Turkey 3
Published in: Cesk Slov Neurol N 2019; 82(6): 677-681
Category: Original Paper
doi: 10.14735/amcsnn2019677

Overview

Aim: To evaluate the choroidal thickness (CT) in patients with Parkinson’s dis­ease (PD) compared to healthy individuals and to investigate the relationship between the dis­ease duration and the CT.

Materials and methods: The study group included 24 right eyes of 24 PD patients and the control group included 25 right eyes of 25 healthy individuals. The CT was measured in both groups us­­ing spectral domain optical coherence tomography (SD-OCT) at 6 points: the foveal centre and at 500-µm intervals temporal (3 points) and nasal (2 points) to the foveal centre. The groups were compared in terms of CT values and group analyses were performed. The cor­relation between the PD duration and the CT was also evaluated.

Results: The mean age of the 24 PD patients (14 males) was 67.5 ± 12.8 years and the mean age of the 25 healthy individuals in the control group (13 males) was 66.1 ± 9.7 years. There were no significant dif­ferences between the groups in terms of age or gender (P = 0.59 and P = 0.768). The PD patients had significantly increased CT values subfoveal (P = 0.04), 500 µm nasal (P = 0.03), and 500, 1,000 and 1,500 µm temporal to the foveal centre (P = 0.02, P = 0.02, P = 0.02, resp.). No cor­relation was detected between the PD duration and the CT (P > 0.05).

Conclusion: The choroidal thickness may increase in PD compared with healthy individuals. However, more studies are needed to cor­roborate our findings and to as­sess the underly­­ing pathophysiology.


帕金森氏病的脉络膜厚度会改变吗?

目的:评估帕金森病(PD)与健康个体相比的脉络膜厚度(CT),并研究疾病持续时间与CT之间的关系。

材料和方法:研究组包括24名PD患者的24个右眼,对照组包括25名健康个体的25个右眼。两组均使用频谱域光学相干断层扫描(SD-OCT)在6个点处测量CT:中央凹中心和距中央凹中心的时间间隔(3个点)和鼻腔(2个点)间隔500 µm。比较各组的CT值,并进行组间分析。还评估了PD持续时间和CT之间的相关性。

结果:24名PD患者(14名男性)的平均年龄为67.5±12.8岁,对照组中25名健康个体的平均年龄(13名男性)为66.1±9.7岁。两组之间在年龄或性别方面无显著差异(P = 0.59和P = 0.768)。 PD患者的中央凹下CT值(P = 0.04),鼻中央500 µm(P = 0.03)以及距中央凹中心的颞侧分别为500、1,000和1,500 µm(分别为P = 0.02,P = 0.02,P = 0.02)。PD持续时间和CT之间未发现相关性(P> 0.05)。

结论:与健康人相比,PD的脉络膜厚度可能增加。然而,需要更多的研究来证实我们的发现和评估潜在的病理生理学。

关键词:脉络膜厚度–光学相干断层扫描

Keywords:

choroidal thickness – optical coherence tomography

Introduction

Parkinson’s dis­ease (PD) is the second most com­mon neurodegenerative disorder after Alzheimer’s and is characterized by the progres­sive loss of dopaminergic neurons [1,2]. It is reported to have a preva­lence of 3% and an incidence of 8– 18 per 100,000 [2]. Although the motor symp­toms are more prominent, visual symp­toms may be observed even in the preclinical stage [1]. Some retinal structural changes in PD have been detected with optic coherence tomography (OCT) mea­surements, and retinal nerve fibre layer (RNFL) and macular thin­n­­ing have been reported [3– 6]. In addition to these structural changes, functional los­ses such as decreased visual acuity, reduced colour vision and contrast sensitivity, and impaired electrophysiological tests have also been reported [7,8]. Therefore, it is believed that the evaluation of ocular structures such as the retina and choroid may provide important information about the severity and duration of PD. Although there are many studies on the visual symp­toms of PD and the changes it causes in the retina, there are few studies in the literature on its ef­fect on the choroid [1,9– 11].

The choroid is located between the reti­na and sclera and is one of the most vascularized tis­sues in the human body. The choroid plays important roles in the oxygenation and feed­­ing of the outer retina, thermal regulation of the retina, elimination of retinal waste material and the secretion of growth factors. Thus, structural­ly and functional­ly healthy choroid tis­sue is critical for retinal functions [12]. The recently developed enhanced depth imag­­ing-OCT (EDI-OCT) method provides in-depth images of the choroid in addition to all retinal layers [13].

The aim of the present study was to use EDI-OCT to evaluate the CT in PD patients compared to healthy individuals and investigate whether CT is as­sociated with PD duration.

Materials and methods

This prospective study was conducted at the Kirşehir Ahi Evran University Train­­ing and Research Hospital‘s Ophthalmology and Neurology departments between January and March 2016. The dia­gnosis of PD was made by neurologists the Neurology Department accord­­ing to United Kingdom Parkinson’s Dis­ease Society Brain Bank Criteria [14]. The study included 24 right eyes of 24 PD patients who were refer­red by neurologists and 25 right eyes of 25 healthy age- and gender-matched individuals. All patients were informed about the study and they provided written consent. The study adhered to the principles of the Declaration of Helsinki and was approved by the institutional ethics com­mittee. All participants underwent detailed ophthalmologic examination at the ophthalmology outpatient clinic includ­­ing best cor­rected visual acuity measurement us­­ing a Snel­len chart, intraocular pres­sure (IOP) measurement us­­ing Goldmann applanation tonometry and slit-lamp and dilated fundus examination. The CT measurements were obtained us­­ing the EDI mode of a spectral domain OCT device (Heidelberg Engineering, Heidelberg, Germany). All measurements were performed in the morn­­ing to avoid diurnal fluctuations in CT [15]. Individuals with visual acuity of 20/ 25 or better were included in the study.

Inclusion criteria

Subjects who did not meet the exclusion criteria and had a cor­rected distance visual acuity of 20/ 25 or above, spherical refractive er­ror of – 1.5 to +1.5 dioptres and an IOP of 21 m­m Hg or less were included in the study.

Exclusion criteria

Patients with a refractive er­ror > ± 1.5 dioptres, choroidal neovascularization or any other macular/ retinal dis­eases that might af­fect the vision, intraocular inflam­mation and/ or infection; a history of any type of intraocular surgery, trauma, serious eye dis­ease (corneal dis­ease, glaucoma, serious cataract) or any systematic dis­ease that might af­fect the eye (such as diabetes mel­litus, arterial hypertension, vasculitis); or a history of smok­­ing and alcohol use, cof­fee addiction, or use of vasoactive drugs were excluded.

Optic coherence tomography protocol

Images were acquired at λ = 840 nm, 40,000 A-scan/ s, 7 µm axial and 14 µm transverse resolution us­­ing a Heidelberg spectral domain OCT device with 6.3.3.0 software. The CT values of all participants were measured manual­ly by the same researcher (Ç.Ö.) as the distance between the outer reflection of the retinal pigment epithelium and the in­ner border of the sclera us­­ing the digital marker provided by the device software in EDI-OCT mode (Fig. 1). The cros­s-sections were measured in the subfoveal (SF) area and at 500-µm intervals temporal and nasal of the fovea. Three mea­surements were obtained at 500 µm (T500), 1,000 µm (T1000), and 1,500 µm (T1500) temporal of the foveal centre. Two measurements were performed at 500 µm (N500) and 1,000 µm (N1000) nasal of the foveal centre (Fig. 1).

Choroidal thickness measurements performed at 6 points at 500-μm intervals in the optic coherence tomography cross-section.<br>
Obr. 1. Měření tloušťky cévnatky bylo provedeno v 6 bodech s 500μm intervaly na řezu snímku získaném optickou koherenční
tomografií.
1. Choroidal thickness measurements performed at 6 points at 500-μm intervals in the optic coherence tomography cross-section.
Obr. 1. Měření tloušťky cévnatky bylo provedeno v 6 bodech s 500μm intervaly na řezu snímku získaném optickou koherenční tomografií.

Statistical analysis

Categorical variables were expres­sed as frequency and percentage values. Continuous variables were presented as mean, standard deviation, median, minimum and maximum values. The Shapiro-Wilk test was used to determine whether the continuous variables were distributed normal­ly. The cor­relations between categorical variables were evaluated us­­ing Pearson’s chi-square analysis. For independent variables, intergroup comparisons were performed us­­ing the Man­n-Whitney U test. Spearman cor­relation analysis was used to detect cor­relations between the variables. A P value < 0.05 was considered statistical­ly significant. Analy­ses were done us­­ing NCSS 11 (Number Cruncher Statistical System, 2017 Statistical Software) and MedCalc Statistical Software version 18 (MedCalc Software bvba, Ostend, Belgium).

Results

The study group included 24 right eyes of 24 PD patients and the control group 25 right eyes of 25 subjects. The mean age of the PD patients was 67.5 ± 12.8 years, and the mean age of the control group was 66.1 ± 9.7 years. There was no significant dif­ference between the mean age of the groups (P = 0.59). There were 10 women and 14 men in the PD group and 12 women and 13 men in the control group (P = 0.768). The mean dis­ease duration was 3.5 ± 1.9 years in the study group (Tab. 1).

1. Demographic and clinical characteristics of study participants.
Demographic and clinical characteristics of study participants.
P < 0,05 is significant
N – number; N/A – not applicable; SD – standard deviation

The choroid was significantly thicker in the PD group at SF (P = 0.04), N500 (P = 0.03), T500 (P = 0.02), T1000 (P = 0.02), and T1500 (P = 0.02). The dif­ference at N1000 was not statistical­ly significant (P = 0.05) (Tab. 2).

2. The comparison of choroidal thickness values of groups.
The comparison of choroidal thickness values of groups.
N – number of eyes; CTN500 – choroidal thickness at 500 μm nasal of the fovea; CTN1000 – choroidal thickness at 1,000 μm nasal of the fovea; CTT500 – choroidal thickness at 500 μm temporal of the fovea; CTT1000 – choroidal thickness at 1,000 μm temporal of the fovea; CTT1500 – choroidal thickness at 1,500 μm temporal of the fovea; SD – standard deviation; SF CT – foveal choroidal thickness

The cor­relation between the CT measurement and dis­ease duration in the PD group was also investigated and no statistical­ly significant cor­relation was found (SF [P = 0.544], N500 [P = 0.664], N1000 [P = 0.549], T500 [P = 0.511], T1000 [P = 0.685], T1500 [P = 0.791]) (Tab. 3).

3. Correlation between choroidal thickness mea surement and disease duration in Parkinson‘s disease.
Correlation between choroidal
thickness mea surement and disease
duration in Parkinson‘s disease.
CTN500 – choroidal thickness at 500 μm nasal of the fovea; CTN1000 – choroidal thickness at 1,000 μm nasal of the fovea; CTT500 – choroidal thickness at 500 μm temporal of the fovea; CTT1000 – choroidal thickness at 1,000 μm temporal of the fovea; CTT1500 – choroidal thickness at 1,500 μm temporal of the fovea; SF CT – foveal choroidal thickness

Discus­sion

Visual symp­toms are among the non-motor signs of PD and can be observed even in the preclinical stage of the disease [1]. Earlier studies demonstrated RNFL and macular thin­n­­ing in PD patients [1,3– 6]. Moreover, visual evoked potential and electroretinography measurements indicated foveal retinal ganglion cell damage [16]. In light of these data, the present study was designed to provide important information about the severity and duration of PD, a neurodegenera­tive dis­ease, by evaluat­­ing ocular structures such as the retina and choroid. Although there are many studies on the visual symp­toms of PD and the changes it causes in the retina, little research was published about its ef­fect on the choroid [1,9– 11]. These studies yielded conflict­­ing results regard­­ing structural measurements of the choroid [1,9– 11].

In our study, the SD-OCT measurements of the CT were greater in PD patients than in the healthy subjects in all 6 points as­ses­sed. The dif­ferences were statistical­ly significant at all points except 1,000 µm nasal of the fovea.

Eraslan et al measured the CT in 22 PD patients and 25 healthy participants us­­ing SD-OCT and determined that the choroid was thin­ner at all measured points in PD patients [9]. Moschos et al also used the SD-OCT to evaluate the choroid, RNFL and ganglion cell complex (GCC) thicknes­ses in 31 PD patients and 25 healthy individuals and reported RNFL, GCC, and choroidal thin­n­­ing in all regions in PD [1].

In contrast to those two studies, a study includ­­ing 50 PD patients and 54 healthy individuals showed that PD patients had higher macular and peripapil­lary CT values measured us­­ing swept-source OCT (SS-OCT) [11]. In another study utiliz­­ing SS-OCT, the results of 40 PD patients and 80 healthy participants were published and PD patients had greater CT values at all 4 points measured in the peripapil­lary region [10]. The increase in CT observed in our study is consistent with the results of these SS-OCT studies.

The researchers who observed increased or decreased CT attributed their findings to various systemic and histopathological changes observed in PD patients. PD is known to cause changes in the peripheral and autonomic nervous systems, result­­ing in symp­tomatic orthostatic hypotension in 20– 58% of patients [17]. Moreover, dopamine agonists used in the treatment of PD were reported to cause arterial hypotension [18]. Eraslan et al stated that lower CT in PD could be due to ir­regularities in the choroidal blood flow as­sociated with hypo­perfusion and the hypotensive ef­fect of dopamine agonists used in PD treatment [9]. Moschos et al reported that thin­n­­ing of the choroidal tis­sue could occur as a result of the synergistic ef­fect of vascular anomalies and neurodegeneration [1].

However, a clinicopathological study found hyaline thicken­­ing in the white matter of the brain and enlarged perivascular spaces in PD patients compared with healthy individuals [19]. The results of this study support an increased CT in PD patients. Consistent with the literature, Satue et al observed an increased CT in PD patients and stated that although ultrastructural changes in the choroidal tis­sue in PD could not be ful­ly explained, the increase in the CT despite hypoperfusion in these patients might be due to changes in the density of perivascular con­nective tis­sue [11].

In our study, we found that the choroid was significantly thicker in PD patients at most of the measured points. This may be attributed to the perivascular enlargement and increase in con­nective tis­sue reported in PD patients in the above-mentioned studies. This hypothesis can only be definitively tested by histopathological examination of the choroid. The choroid is known to be vital­ly important for healthy retinal tis­sue. It plays a key role in oxygenat­­ing and feed­­ing the outer retina, eliminat­­ing retinal waste and secret­­ing growth factors [12]. Therefore, thicken­­ing of the vascular choroidal tis­sue that supports the retina may occur to compensate for the retinal atrophy observed in PD patients.

In the present study, we also investigated whether CT was as­sociated with PD duration. To the best of our knowledge, the cor­relation between dis­ease duration and CT was previously evaluated only by Eraslan et al, who reported that choroidal thin­­­n­­ing was as­sociated with dis­ease duration [9]. Unlike this article, there was no significant cor­relation between the PD duration and CT in our study.

Our study has some limitations. First, we questioned our patients regard­­ing the presence of arterial hypertension and used it as an exclusion criterion. However, we did not ask about arterial hypotension. Hypotension and hypoperfusion due to autonomic dysfunction are com­mon in PD [18]. This could also af­fect the choroidal perfusion. The second limitation is that we did not determine the stage of PD. Therefore, our study group may not have been homogeneous. Furthermore, we did not measure axial length in our patients but excluded patients with myopia and hypermetropia with a spherical equivalent of ± 1.5 or higher to minimize the ef­fect of axial length. Another pos­sible limitation is that the sample size of our study was relatively smal­l.

In conclusion, CT may increase in PD due to ultrastructural changes such as perivascular enlargement and choroidal compensation for atrophic changes in the retina. However, more studies with larger patient groups and fewer limitations are needed to cor­roborate our findings.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE “uniform requirements” for biomedical papers.

Çağlar Öktem, MD

Department of Ophthalmology

Alaaddin Keykubat University

Alanya Education and Research Hospital

074 00 Antalya

Turkey

e-mail: cglroktm@gmail.com

Accepted for review: 12. 8. 2019

Accepted for print: 30. 10. 2019


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