Optical coherence tomography in patients with Wilson’s disease: A single center, prospective study

doi:10.21203/rs.3.rs-2225780/v1

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Optical coherence tomography in patients with Wilson’s disease: A single center, prospective study

https://doi.org/10.21203/rs.3.rs-2225780/v1

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Background: Morphological changes of retina in patients with Wilson’s disease

(WD) can be found by optical coherence tomography (OCT), and such changes have significant differences between neurological forms（NWD ) and hepatic forms (HWD) of WD. We aimed to evaluate the relationship between morphological parameters of retina and brain magnetic resonance imaging (MRI) changes, course of disease, type of disease and sexuality in WD. This is a single center, prospective study including forty-six WD patients and forty healthy controls (HC). We employed theGlobal Assessment Scale (GAS) to assess the the neurological sign of WD patients.

Results: NWD had thinner superior parafovea zone (108.07±6.89 um vs. 114.40±5.54 um, p<0.01), temporal parafovea zone (97.17±6.65 um vs. 103.60±4.53 um, p<0.01), inferior parafovea zone (108.114±7.65 um vs. 114.93±5.84 um, p<0.01) nasal parafovea zone (105.53±8.01 um vs. 112.10±5.44 um, p<0.01) in inner retina thickness than HWD. The course of disease influenced the retina thickness, male patients had thinner inner retina thickness than female patients.

Conclusion: Our results demonstrated that WD had thinner inner retina thickness than HC and NWD had thinner inner retina thickness than HWD. We spectualted the thickness of inner retina layer may a potential useful biomarker for NWD.

Wilson's disease

Optical Coherence Tomography (OCT)

duration

magnetic resonance imaging (MRI)

Wilson’s disease (WD) is an inherited autosomal recessive disorder that leads to copper accumulation in the liver, brain, cornea, and other organs[1]. Kayser-Fleischer ring (KFR) is typical for WD and represents deposition of copper in the posterior corneal layers. Sunflower cataracts[2], optic neuritis, optic disc pallor and exotropia[3] are rare ophthalmological manifestations. Deposits of copper accumulate over the course of the disease and cause injuries to different organs[4–6]. Pathological changes in the brain in patients with WD are mainly located in the basal ganglia, but copper may accumulate in other central nervous system structures[7, 8].

Recent studies demonstrated morphological changes of the retina in patients with WD using optical coherence tomography (OCT)[1, 9–11]. Study showed that significant negative correlation was found between OCT parameters and neurological impairment according the UWDRS scale in WD[1], patients with MRI changes in brain had thinner macular and retinal nerve fibers in WD[9]. On the basis of the previous studies, we adjust the mode of OCT, focus on research in different layers of retina, investigate the relationship between morphalogical parameters of retina and brain MRI changes, course of disease, type of disease and sexuality in Chinese WD patients.

All patients provided informed consent. We collected 46 WD patients admitted to the First Affiliated Hospital of Guangdong pharmaceutical university from June 2021 to April 2022. Four patients were excluded because they could not cooperate with the OCT examination because of severe tremor. Forty-two WD patients were enrolled in the study, 21 males and 21 females. We also recruited 40 sexy-age match healthy controls (HC). All participants were Han nationality Chinese. All patients met the diagnostic criteria for WD[4]. Exclusion criteria: (1) a contraindication to the use of 1% tripicamide. (2) a history of prior ocular trauma. (3) patients that can not cooperate with severe involuntary movements (such as severe rest tremor). (4) patients were younger than 15 years old. Demographic and clinical characteristics of the 42 WD patients are shown in Table 1.

Table 1

Clinical and demographic features of patients with neurological and hepatic form of Wilson's disease
Feature	Neurological form of disease	Hepatic form of disease	P value
Number^b	27(64%)	15(36%)
Gender(male/female)^a	16/11	4/11	0.043^c
Age (years)^a	30.56 ± 10.12	30.53 ± 10.00	0.995
Age at onset (years)^a	19.96 ± 9.12	19.00 ± 11.02	0.773
Age at diagnosis (years)^a	20.39 ± 9.43	19.00 ± 11.08	0.681
Disease duration (years)^a	10.10 ± 6.79	11.40 ± 4.25	0.513
Latency from diagnosis to treatments (years)^a	1.01 ± 3.24	1.40 ± 4.33	0.757
Treatment duration^a	9.14 ± 7.05	11.13 ± 3.77	0.323
^a values presented as means ± SDs in brackets.
^b values presented as number of patients with percentage in brackets.
^cp < 0 .05.

According to the type of clinical presentation, the WD patients were divided in two groups, group of neurological (NWD) and group of hepatic (HWD). We employed the Global Assessment Scale (GAS) to assess the the neurological severity of WD patients[12]. Each participant underwent OCT using RTVue XR Avanti System (Optovue, Inc, Fremont, CA, USA) with AngioVue software (version 2018,1,1,63). All OCT scans were performed by the same experienced operator. The operator reviewed all the OCT images, in order to identify segmentation errors, artifacts and poor image quality, thus ensuring that only proper images were finally included in our study. The scanning areas used in this study were 3 × 3 mm (Angio Retina [3.0]) and 6 × 6 mm (HD Angio Retina [6.0]) both centered on the fovea (Fig. 1).

After the completion of the scan process, the following measured parameters were recorded: Full Retina Thickness: inner limiting membrane layer to retinal pigment epithelium layer (ILM-RPE), Inner Retina Thickness: ILM to inner plexiform layer (ILM-IPL).

All WD patients underwent 3.0T brain MRI with a GE Discovery MR750, GE Medical Systems. All the patients were performed the following sequences: T1- and T2- weighted scans, fluid attenuated inversion recovery (FLAIR) and Susceptibility Weighted Imaging (SWI). The presence of lesions on MRI in the following structures was collected: basal ganglia, cerebellum, midbrain, and other localisations in white matter.

Statistical analysis

To avoid internal correlations, data were analyzed by patients using mean values of measurements taken from both eyes. The data are presented as means ± standard deviation (M ± SD). Comparisons of the OCT parameters and demographic features were performed using the Student's t test. Logistic regression analysis was used for the influence on examined OCT parameters. Statistical analysis was performed using SPSS 23, and p-values below 0.05 were considered statistically significant.

Forty-two WD patients (mean age 30.54 ± 9.83 years) were divided in two groups: NWD (11 females and 16 males, mean age 30.56 ± 10.12 years) and HWD (11 females and 4 males, mean age 30.53 ± 10.00 years). HC comprised 16 females and 24 males, with a mean age of 30.42 ± 7.37 years.

In order to assess the relationship between OCT parameters and course of disease, all recruited patients are stratified into three groups: course of disease shorter than 5 years (<5 y group), 5–10 years (5–10 y group), longer than 10 years (>10 y group). There is no significant difference in onset of age, age of diagnosis, course of disease, latency from diagnosis to treatment and treatment duration between NWD and HWD.

1. WD Patients had thinner inner retina layer than HC

Compared to HC, WD had thinner superior parafovea zone (110.33 ± 7.07 um vs. 114.45 ± 6.32 um, P<0.01), thinner temporal parafovea zone (99.46 ± 6.69 um vs. 103.15 ± 4.86 um, P<0.01), thinner inferior parafovea zone (110.57 ± 7.72 um vs. 114.90 ± 4.47 um, P<0.01), thinner nasal parafovea zone (107.88 ± 7.80 um vs. 112.50 ± 5.40 um, P<0.01), thinner superior perifovea zone (99.78 ± 7.60 um vs. 104.45 ± 10.01 um, P = 0.021), thinner temporal perifovea zone (85.53 ± 5.22 um vs. 88.65 ± 7.31um, P = 0.030) and thinner nasal perifovea zone (114.94 ± 19.93 um vs. 122.45 ± 12.09 um, P = 0.044) than HC in inner retina layer (Table 2).

Table 2

OCT Parameters in WD, NWD, HWD and HC
(um)	HC	WD	HWD	NWD	P value
FRL	M ± S	M ± S	M ± S	M ± S	P value
S1	324.90 ± 13.85	326.36 ± 13.97	329.46 ± 16.21	324.64 ± 12.55	0.503
T1	311.50 ± 10.61	311.15 ± 14.23	314.73 ± 15.85	309.16 ± 13.14	0.388
I1	320.05 ± 11.94	321.33 ± 15.50	323.90 ± 18.44	319.90 ± 13.79	0.618
N1	323.95 ± 11.75	324.60 ± 13.72	328.73 ± 13.74	322.31 ± 13.41	0.289
S2	288.45 ± 16.88	287.36 ± 13.54	291.20 ± 14.41	285.24 ± 12.81	0.457
T2	272.85 ± 17.97	269.75 ± 12.50	270.40 ± 14.14	269.38 ± 11.76	0.652
I2	272.65 ± 16.16	276.00 ± 15.23	277.03 ± 14.69	275.42 ± 15.76	0.601
N2	300.75 ± 18.47	297.94 ± 49.25	308.46 ± 16.60	292.09 ± 59.81	0.378
IRL
s1	114.45 ± 6.32	110.33 ± 7.07^#	114.40 ± 5.54	108.07 ± 6.89*⁺	0.000
t1	103.15 ± 4.86	99.46 ± 6.69^#	103.60 ± 4.53	97.16 ± 6.65*⁺	0.000
i1	114.90 ± 4.47	110.57 ± 7.72^#	114.93 ± 5.84	108.14 ± 7.65*⁺	0.000
n1	112.50 ± 5.40	107.88 ± 7.80^#	112.10 ± 5.44	105.53 ± 8.01*⁺	0.000
s2	104.45 ± 10.01	99.78 ± 7.60^##	103.33 ± 6.79	97.81 ± 7.42*	0.010
t2	88.65 ± 7.31	85.53 ± 5.22^##	86.90 ± 4.82	84.77 ± 5.37	0.054
i2	100.95 ± 9.18	99.17 ± 6.86	101.73 ± 6.67	97.75 ± 6.67	0.192
n2	122.45 ± 12.09	114.94 ± 19.93^##	121.13 ± 7.26	111.50 ± 23.75*	0.026
Compared to HC, # means p<0.01, ## means p<0.05. Compared to HC, * means p<0.01. Compared to HWD, + means p<0.01. S1,T1,I1,N1 (s1,t1,i1,n1) mean superior, temporal, inferior, and nasal parafovea zone of full retina layer (inner retina layer) in 3 × 3 mm centered on the fovea, S2,T2,I2,N2 (s2,t2,i2,n2) mean superior, temporal, inferior, and nasal perifovea zone of full retina layer (inner retina layer) in 6 × 6 mm centered on the fovea. NWD=neurological form group, HWD༝hepatic form group, HC༝healthy controls. M ± S༝Means ± Standard Deviation. FRL༝full retina layer, IRL༝inner retina layer.

2. NWD had thinner inner retina layer than HWD

Compared to HC, NWD had thinner superior parafovea zone (108.07 ± 6.89 um vs. 114.45 ± 6.32 um, p<0.01), temporal parafovea zone (97.16 ± 6.65 um vs. 103.15 ± 4.86 um, p<0.01), inferior parafovea zone (108.14 ± 7.65 um vs.114.90 ± 4.47 um, p<0.01 ), nasal parafovea zone (105.53 ± 8.01 um vs. 112.50 ± 5.40 um, p<0.01), superior perifovea zone (97.81 ± 7.42 um vs. 104.45 ± 10.01 um, p<0.01) and nasal perifovea zone (111.50 ± 23.75 um vs. 122.45 ± 12.09 um, p<0.01) in inner retina layer (Table 2).

Meanwhile, compared to HWD, NWD had thinner superior parafovea zone (108.07 ± 6.89 um vs. 114.40 ± 5.54 um, p<0.01), temporal parafovea zone (97.16 ± 6.65 um vs. 103.60 ± 4.53 um, p<0.01), inferior parafovea zone (108.14 ± 7.65 um vs.114.93 ± 5.84 um, p<0.01 ), nasal parafovea zone (105.53 ± 8.01 um vs. 112.10 ± 5.44 um, p=0.01) in inner retina layer (Table 2).

In conclusion, the morphological change of retina occurs at a later stage of the disease, thinning of inner retina layer in HWD may be associated with neurological system injury. Therefore, the thickness of inner retina layer may a potential indicators for the monitoring of the disease progression.

3. Male patients had thinner inner retina layer than female patients in WD

Previous study showed that WD severity associated with gender and course of disease[13]. For the reasons stated above, we would like to investigate whether the OCT parameters are also gender-related. In our study we found that compared to female, male had thinner superior perifovea zone (97.16 ± 7.92 um vs.102.40 ± 6.44 um, p=0.024), inferior perifovea zone (96.64 ± 6.76 um vs. 101.71 ± 6.11 um, p༝0.015), nasal perifovea zone (114.32 ± 7.99 um vs. 121.16 ± 7.05 um, p<0.01) in inner retina layer (Table 3).

Table 3

OCT parameters in male and female
(um)	male	female	male vs. female
FRL	M ± SD	M ± SD	P value
S1	328.76±11.76	323.97±15.79	0.272
T1	314.59±13.04	307.71±14.85	0.119
I1	324.57±14.72	318.09±15.94	0.179
N1	327.54±12.23	321.66±14.77	0.168
S2	285.45±13.44	289.28±13.68	0.365
T2	271.59±11.96	267.90±13.04	0.345
I2	275.90±17.40	276.09±13.13	0.968
N2	303.34±13.07	307.07±15.75	0.409
IRL
s1	110.09±7.31	110.57±7.00	0.830
t1	99.61±6.92	99.31±6.62	0.883
i1	110.02±8.31	111.11±7.25	0.652
n1	108.16±8.17	107.59±7.60	0.816
s2	97.16±7.92	102.40±6.44	0.024
t2	85.26±5.96	85.81±85.81	0.739
i2	96.64±6.76	101.71±6.11	0.015
n2	114.32±7.99	121.16±7.05	0.005
S1,T1,I1,N1 (s1,t1,i1,n1) mean superior, temporal, inferior, and nasal Parafovea in full retina layer (inner retina layer), S2,T2,I2,N2 (s2,t2,i2,n2) mean superior, temporal, inferior, and nasal Perifovea in full retina layer (inner retina layer). M ± S=Means ± Standard Deviation. FRL༝full retina layer, IRL༝inner retina layer. Statistically significant differences are represented in bold.

4. Longer duration with thinner full retina layer in WD

There is no significant difference between <5 y group and 5–10 y group, however, compared to <5 y group, >10 y group had thinner superior parafovea zone (335.28 ± 8.03 um vs. 322.25 ± 15.78 um, p=0.044) and thinner nasal parafovea zone (334.00 ± 10.63 um vs. 320.78 ± 14.76 um, p༝0.038) in full retina layer (Table 4). It seems that the thickness of full retina layer is assosited with the course of disease and patients with longer course of disease are more likely to occur morphalogical change of retina.

Table 4

OCT Parameters in different disease duration
(um)	<5 y group	5–10 y group	>10 y group	P vaule
FRL	M ± SD	M ± SD	M ± SD
S1	335.28±8.03	332.59±12.51	322.25±15.78^#	0.152
T1	318.64±15.50	316.54±10.98	307.39±15.97	0.262
I1	329.78±14.89	326.13±14.79	317.67±17.13	0.851
N1	334.00±10.63	330.27±12.14	320.78±14.76	0.258
S2	297.71±6.45	289.59±15.13	285.96±12.93	0.059
T2	277.57±13.62	272.00±12.65	267.46±12.75	0.994
I2	282.28±9.63	277.63±12.85	275.17±20.10	0.411
N2	270.21±119.35	311.72±15.29	301.07±14.62^#	0.002
IRL
s1	114.07±7.41	111.13±6.28	110.39±7.89	0.556
t1	103.64±6.79	98.81±6.89	99.39±7.38	0.640
i1	115.71±7.65	109.72±7.96	110.21±8.61	0.854
n1	112.42±7.92	109.18±7.07	107.28±8.40	0.581
s2	103.35±6.03	98.72±9.27	100.71±7.59	0.480
t2	88.71±5.77	84.45±5.55	85.42±5.63	0.803
i2	101.07±5.30	98.04±5.61	98.57±8.63	0.642
n2	103.57±46.08	118.95±8.76	114.46±22.44	0.007
Compared to <5 y group, # means p<0.05. S1,T1,I1,N1 (s1,t1,i1,n1) mean superior, temporal, inferior, and nasal parafovea zone of full retina layer (inner retina layer) in 3 × 3 mm centered on the fovea, S2,T2,I2,N2 (s2,t2,i2,n2) mean superior, temporal, inferior, and nasal perifovea zone of full retina layer (inner retina layer) in 6 × 6 mm centered on the fovea. M ± S=Means ± Standard Deviation. FRL༝full retina layer, IRL༝inner retina layer.

5. More extensive brain injury with thinner inner retina layer in WD

Previous study had detected macular and retinal nerve fibres were thinner and markedly different in those with MRI changes[9], we using a slightly different approach, divided patients into three groups based on the different regions injury on visual brain MRI: group 1. present of basal ganglia injury but absent of brainstem injury (ABI), group 2. present of basal ganglia injury and brainstem injury (PBI), group 3. normal (no visual brain MRI injury, MRI-).

In our study, there had no significant difference with OCT parameters between MRI- and MRI abnormal group (Table 5). PBI had thinner nasal parafovea zone (103.00 ± 4.08 um vs. 113.16 ± 6.43um, p=0.022) in inner retina layer than MRI- (Table 6). But there have no significant differences between ABI and PBI in OCT parameters (Table 6).

Table 5

OCT Parameters in MRI + and MRI-
(um)	MRI+	MRI-	MRI+ vs. MRI-
FRL	M ± SD	M ± SD	P value
S1	328.09±15.12	327.00±10.69	0.869
T1	313.74±14.86	309.41±11.44	0.510
I1	324.42±16.06	318.00±13.97	0.373
N1	325.51±14.66	327.16±12.01	0.800
S2	288.98±14.16	287.41±10.21	0.801
T2	272.62±13.34	264.83±5.79	0.175
I2	279.09±17.18	269.25±5.72	0.180
N2	294.74±60.79	306.16±12.39	0.377
IRL
s1	111.14±6.70	114.58±6.52	0.281
t1	100.72±6.13	99.50±9.06	0.689
i1	112.31±6.67	110.33±10.93	0.564
n1	108.16±7.84	113.16±6.43	0.157
s2	100.70±6.80	103.58±8.91	0.381
t2	86.70±4.84	85.50±4.85	0.599
i2	100.61±6.52	98.75±5.36	0.521
n2	114.11±23.84	121.16±9.45	0.486
S1,T1,I1,N1 (s1,t1,i1,n1) mean superior, temporal, inferior, and nasal Parafovea in full retina layer (inner retina layer), S2,T2,I2,N2 (s2,t2,i2,n2) mean superior, temporal, inferior, and nasal Perifovea in full retina layer (inner retina layer). M ± S=Means ± Standard Deviation. FRL༝full retina layer, IRL༝inner retina layer.

Table 6

OCT parameters in different regions injury on visual brain MRI
(um)	PBI	BGI	MRI-	P vaule
FRL	M ± SD	M ± SD	M ± SD
S1	326.33±9.31	328.59±16.56	327.00±10.69	0.934
T1	310.161±0.85	314.76±15.90	309.41±11.44	0.640
I1	320.161±0.47	325.64±17.35	318.00±13.97	0.514
N1	321.33±9.76	326.71±15.78	327.16±12.01	0.700
S2	287.75±13.05	289.33±14.75	287.41±10.21	0.940
T2	273.52±14.68	269.50±6.99	264.83±5.79	0.319
I2	277.58±13.29	279.52±18.41	264.83±5.79	0.400
N2	305.161±1.55	291.76±68.77	306.16±12.39	0.795
IRL
s1	107.50±3.39	112.19±7.10	114.58±6.52	0.170
t1	97.41±5.07	101.66±6.18	99.50±9.06	0.361
i1	107.91±4.04	113.57±6.81	110.33±10.93	0.224
n1	103.00±4.08	109.64±8.09^#	113.16±6.43	0.061
s2	99.00±8.42	101.19±6.42	103.58±8.91	0.555
t2	84.50±3.33	87.33±5.08	85.50±4.85	0.391
i2	100.75±10.11	100.57±5.45	98.75±5.36	0.815
n2	116.75±8.29	113.35±26.81	121.16±9.45	0.747
Compared to MRI-, # means p<0.05. S1,T1,I1,N1 (s1,t1,i1,n1) mean superior, temporal, inferior, and nasal parafovea zone of full retina layer (inner retina layer) in 3 × 3 mm centered on the fovea, S2,T2,I2,N2 (s2,t2,i2,n2) mean superior, temporal, inferior, and nasal perifovea zone of full retina layer (inner retina layer) in 6 × 6 mm centered on the fovea. BGI=basal ganglia injury, PBI༝present of brainstem injury, MRI-=no visual brain MRI injury. M ± S༝Means ± Standard Deviation. FRL༝full retina layer, IRL༝inner retina layer.

Our results indicated that WD exhibited thinner inner retina layer compared to HC and that NWD exhibited a thinner inner retina layer compared to HWD. Simultaneously, we found different inner retina layer thickness in different gender grouping and different abnormal brain MRI subgroup.

Morphological changes of retina in patients with WD can be found by OCT[9], and such changes have significant differences between NWD and HWD[1]. OCT is a non-invasive high resolution optical imaging technology, the details of the principles of spectral-domain OCT have been described in previous study[14]. In the last 20 years, development of OCT have fundamentally changed retinal diagnosis[15, 16]. Currently, due to the lack of direct access, human cerebral microvascular alterations are difficult to non-invasively monitor in vivo. Nevertheless, since the vasculature of the retina and brain is similar in its anatomy and physiology[17], changes in the structure and function of the brain and cerebral vessels may lead to changes in retina vessels and morphology. The embryological, structural, and functional continuity of the retina with the central nervous system makes the visual pathway a prime target for potential non-invasive investigations of neurodegeneration, such as the neurodegeneration that occurs in the course of Alzheimer’s disease and multiple sclerosis[18].

Studies showed that retinal nerve fibre layer is thinner in WD compared to HC, and retinal nerve fibre layer is thinner in MRI + compared to MRI-[9, 10]. Albrecht et al. found WD patients has thinner mean thickness of the retinal nerve fibre layer, paramacular region, retinal ganglion cell/inner plexiform layer and inner nuclear layer than matched HC[10]. Langwinska et al. showed that macular and retinal nerve fibre layer were thinner, especially different in those with MRI changes[9]. Our results indicated retinal morphological change by OCT were in line with previous findings[9, 10].

Previous study indicated that macular and retinal nerve fibers layer were thinner in patients with changes on MRI than in patients without changes[9]. In our study we found that there is no significant difference between patients with MRI- and patients with MRI+ (ABI + PBI). However, as we further divided the patients into three groups(ABI, PBI and MIR-) based on the different regions injury on visual brain MRI, patients with more severe brain injury had thinner inner retina layer. Our results indicated that thinning of inner retina layer in OCT may be related to brain damage and damage severity.

Marina Svetel al. showed that course of disease did not influence the retinal nerve fibers laye thickness[11]. However, in our study, we found that comparing to <5 y group, >10 y group has thinner superior parafovea zone and thinner nasal parafovea zone in full retina layer. We speculated that thinning of full retina layer in patients with longer course of disease is accociated with retinal neurodegeneration caused by excess copper. In summary, with the prolonged course of the disease, the full retina layer gradually became thinner, which may indicate the full retina layer as a potential marker for disease severity of WD.

A study of a large cohort of patients with WD confirmed there was a gender effect in index patients: hepatic presentation was more common in females and neurologic presentation in males[13]. In our study, compared to female, male had thinner inner retina layer, compared to HWD, NWD had thinner inner retina layer, compared to MRI-, MRI + had thinner inner retina layer, these indicated that thinning of inner retina layer may be a biomarker of NWD.

The retina consists of axons and glia without myelin and maybe a good structure for visualizing the degree of neurodegeneration[19]. Direct oxidative stress and apoptosis are principal pathway of copper toxicity in WD, resulting in cell death in the affected tissues[20]. To a certain extent, the excess copper was neutralized by antioxidants, but an elevated level of reactive oxygen species beyond a certain limit might induce undesirable oxidative damage in the cells[21, 22]. Therefore, the observation of significant different of inner retina layer in NWD and HWD supported previous study that chronic copper-related degeneration affected unmyelinated fibers[23].

The main disadvantage of our study is the lack of follow up data. We plan to continue examinations in the future. Because of the small sample size of this study, we can not conclude specific significance of thinning of inner retina layer and full retina layer in WD. Later, we will further expand the sample size, clear and definite the significance of thinning of inner retina layer and full retina layer in WD studies.

Our results demonstrated that WD had thinner inner retina layer than HC, NWD had thinner inner retina layer than HWD. The main disadvantage of our study is the lack of follow up data. We plan to continue examinations in the future. Because of the small sample size of this study, we can not conclude specific significance of thinning of inner retina layer and full retina layer in WD. Later, we will further expand the sample size, clear and definite the significance of thinning of inner retina layer and full retina layer in WD studies.

S1,T1,I1,N1 (s1,t1,i1,n1) mean superior, temporal, inferior, and nasal parafovea zone of full retina layer (inner retina layer) in 3 × 3 mm centered on the fovea

S2,T2,I2,N2 (s2,t2,i2,n2) mean superior, temporal, inferior, and nasal perifovea zone of full retina layer (inner retina layer) in 6 × 6 mm centered on the fovea. NWD

neurological form group

HWD

hepatic form group

healthy controls

M ± S

Means ± Standard Deviation

FRL

full retina layer

IRL

inner retina layer

BGI

basal ganglia injury

PBI

present of brainstem injury

MRI-

no visual brain MRI injury.

Acknowledgements

We would like to thank all the subjects who participated in this study.

Author contributions

WQ-N: data collection, analysis and manuscript writing. CX-L: data collection and manuscript writing. ZH-Z, MF-H: study design, manuscript revision and interpretation of data. SP-D, YQ-H, AQ-L, QY-Y, ZX-P: data collection, analysis and interpretation of data. All authors read and approved the final manusscript.

Funding

The work was supported by Basic and Appiled Basic Research Foundation of Guangdong Province (zhou zhihua, No.2019A1515011314) of China. The funding body had no role or interference in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Data availability

The raw data supporting the conclusions of this article will be made available by the corresponding authors, without undue reservation.

Ethics approval

The study was conducted according to the statement of the Declaration of Helsinki. The use of data for publication was approved by the Ethics Board of the first affiliated hospital, school of clinical Medicine of Guangdong Pharmaceutical University. All patients or parents gave their informed consent to participate.

Consent for publication

Not applicable.

Conflict of interest

The authors have no conflict of interest to declare.

Author details

Department of neurology, The first affiliated hospital, school of clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.

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Editorial decision: Major revision
13 Mar, 2023
Reviewers agreed at journal
23 Jan, 2023
Reviewers invited by journal
17 Nov, 2022
Editor assigned by journal
13 Nov, 2022
First submitted to journal
05 Nov, 2022

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Optical coherence tomography in patients with Wilson’s disease: A single center, prospective study

Status:

Version 1

Abstract

Figures

Background

Methods

Statistical analysis

Result

1. WD Patients had thinner inner retina layer than HC

2. NWD had thinner inner retina layer than HWD

3. Male patients had thinner inner retina layer than female patients in WD

4. Longer duration with thinner full retina layer in WD

5. More extensive brain injury with thinner inner retina layer in WD

Discussion

Limitations

Conclusion

Abbreviations

Declarations

Funding

References

Status:

Version 1