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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 20  |  Issue : 2  |  Page : 82-87

Electrophysiological study of thyroid ocular disorders


1 Depertment ophthalmology, Mansoura Ophthalmic Center, Mansoura Medicine Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Depertment ophthalmology, Mansoura Medicine Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt

Date of Submission10-Oct-2018
Date of Acceptance06-Mar-2019
Date of Web Publication24-Jul-2019

Correspondence Address:
Mona Abdel Kader
Ophthalmology Center, Faculty of Medicine, Mansoura University, 35516 Mansoura
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/DJO.DJO_50_18

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  Abstract 


Purpose The aims of this study were to evaluate the visual evoked potential (VEP) changes in thyroid ocular disorders and to correlate between VEP latencies and thyroid hormones.
Patients and methods The study participants were divided into four groups. Group 1 comprised 50 patients (100 eyes) with subclinical hypothyroidism (29 patients had recent hypothyroidism without treatment, and 21 patients had controlled hypothyroidism with treatment). Group 2 comprised 35 patients (70 eyes) with overt hypothyroidism (20 patients had recent hypothyroidism without treatment, and 15 patients had controlled hypothyroidism with treatment). Group 3 comprised 35 patients (70 eyes) with hyperthyroidism (18 patients had recent hyperthyroidism without treatment, and 17 patients were under treatment). Group 4 comprised 70 patients (140 eyes) with normal thyroid functions as a control group. Flash and pattern VEP and thyroid hormone assay were performed for all patients.
Results There was an increase in the latencies of VEP without statistically significant change in amplitudes in thyroid disorders (groups 1, 2, and 3) compared with the normal control group (group 4). The increase in latencies in group 1 was statistically insignificant (P>0.1), while, in groups 2 and 3, it was statistically significant (P<0.005 and 0.001, respectively). In group 3, there was a positive correlation between latencies and tri-iodothyronine (T3) and thyroxine (T4). The increase in p100 was accompanied with an increase in T3 and T4.
Conclusion VEP can detect the early optic nerve defects in the absence of any neurological or ophthalmological symptoms in thyroid disorders.

Keywords: thyroxine, tri-iodothyronine, visual evoked potential


How to cite this article:
Abdel Kader M, Abass N. Electrophysiological study of thyroid ocular disorders. Delta J Ophthalmol 2019;20:82-7

How to cite this URL:
Abdel Kader M, Abass N. Electrophysiological study of thyroid ocular disorders. Delta J Ophthalmol [serial online] 2019 [cited 2019 Sep 23];20:82-7. Available from: http://www.djo.eg.net/text.asp?2019/20/2/82/263412




  Introduction Top


Thyroid diseases are multiorgan endocrine diseases that lead to metabolic defects including in the eye, brain, nerves, and others [1].

Center nervous system (CNS) defect is an essential consequence of thyroid diseases that has an insidious onset and may occur early [2]. The thyroid disorders affect the CNS through the affection of gene expression, transport through axons and myelin formation [3].

Visual evoked potential (VEP) is a noninvasive test for evaluation of impulse transmission from the optic nerve to the occipital cortex. There are two types of VEP: flash and pattern VEP (FVEP and PVEP, respectively). P100 wave (P means positive, 100 indicates latency at 100 ms) is the main wave in pattern VEP that shows little differences between patients and minimal interocular difference [4].

There is little information about the role of VEP in thyroid diseases that made the authors to evaluate the effects of thyroid dysfunction on VEP parameters and to find the relation between thyroid hormones and VEP responses.

The aims of this study were to detect VEP changes in thyroid disorders and to correlate between VEP latencies and thyroid hormones.


  Patients and methods Top


This study was carried out on patients attending the Outpatient Clinic of Mansoura Medicine Hospital from February 2016 to June 2018. One hundred and ninety patients (190 patients, 380 eyes) with thyroid disorders were included in the study. The study was approved by the Local Ethical Committee of Mansoura University, and all patients signed a written informed consent before participating in the study.

The study participants were divided into four groups. Group 1 had subclinical hypothyroidism, group 2 had overt hypothyroidism, group 3 had hyperthyroidism, and group 4 was normal euthyroid patients.

All patients underwent complete medical and ophthalmological examination, color vision testing using Ishihara plates and screening of the visual field using Humphrey visual field analyzer 640 (Carl Zeiss Co., San leandro, California, USA). A scotoma was defined as at least two adjacent points of at least five-decibel sensitivity loss for each point or as at least one point of at least 10-decibel sensitivity loss. Flash and pattern VEP and thyroid hormone assay were performed for all patients.

Exclusion criteria

Any diseases that might affect the results of VEP, such as diabetes mellitus,  Parkinsonism More Details, eye diseases (severe myopia, astigmatism, cataract, glaucoma, and maculopathy), and history of using miotic/mydriatic eye drops were excluded from the study.

None of the patients had clinical symptoms or signs referable to CNS dysfunction.

Visual evoked potential

VEP was recorded using the German-made Roland Consult Electrophysiological diagnostic system (RETI port 21; Roland Consult, Brandenburg, Germany).

It was carried out according to the International Society for Clinical Electrophysiology of Vision [4]. Patients were informed to wash their hair with shampoo (for clean scalp from oil) before coming to do VEP to decrease skin impedance for better recording of VEP. Standard silver chloride electrodes of 1 cm diameter were used for recording. The positive electrode was connected to the midline of the head at two fingers breadth above the inion (projection at the back of the head). The ground electrode was connected in the midline of the head at the level of the ear lobule. The negative electrode was connected to the middle of the forehead. The sites of the electrodes were cleaned with a cleaning cream before placing the electrodes. The electrodes (silver, cup-shaped) were filled with connecting gel before application. For each eye, two recordings were obtained.

Patients were asked to fix their gaze on the flash generated in Ganzfeld in FVEP (0 dB, 2 Hz, white in color), while, in PVEP, the patient was seated in front of a pattern monitor (check size=1 min, check number 16×16, contrast was 97%) at a distance of 1 m while wearing his reading correcting glasses. They were watched for any gross eye movement or attention lapse during the procedure through the camera in the monitor. Two trials were given for each eye.

Thyroid hormones

Free tri-iodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) tests were performed for each patient.


  Results Top


The study included 190 patients (380 eyes). Their best-corrected visual acuity ranged from 0.8 to 1.00 (Decimal unit) with a refractive error between −1.00 diopter (D) and +1.00 D. The study participants were divided into four groups. Group 1 comprised 50 patients (100 eyes) with subclinical hypothyroidism (29 patients had recent hypothyroidism without treatment, and 21 patients’ hypothyroidism was controlled with treatment; 40 were female individuals aged 20 to 45 years, and 10 were male individuals aged 22 to 43 years). Group 2 comprised 35 patients (70 eyes) who had overt hypothyroidism (20 patients had recent hypothyroidism without treatment, and 15 patients’ hypothyroidism was controlled with treatment; 30 were female individuals aged 18 to 40 years, and five were male individuals aged 25 to 43 years). Group 3 comprised 35 patients (70 eyes) having hyperthyroidism (18 patients had recent hyperthyroidism without treatment, and 17 patients were under treatment; 28 were female individuals aged 25 to 45 years, and seven were male individuals aged 22 to 40 years). Group 4 comprised 70 normal patients (140 eyes, 35 female individuals aged 20 to 45 years and 35 male individuals aged 22 to 43 years).

Normal FVEP consists of successive positive and negative waves: N1, P1, N2P2, N3, and P3 ([Figure 1]). Normal PVEP consists of three waves N75, P100, and N135. N75 means negative wave at latency 75 ms. P100 is the main wave and means positive wave at 100 ms latency. N135 means negative wave at latency 135 ms ([Figure 2]).
Figure 1 Flash visual evoked potential in groups. (a) Flash visual evoked potential in normal (there is normal latency and amplitude). (b) Flash visual evoked potential in hypothyroidism (there is a mild delay in latency with an insignificant reduction in amplitude. (c) Flash visual evoked potential in hyperthyroidism (there is a severe delay in latency with a statistically insignificant reduction in amplitude).

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Figure 2 (a) Pattern visual evoked potential in euthyroidism (there is normal latency and amplitude). (b) Pattern visual evoked potential in hypothyroidism (there is a mild delay in latency with an insignificant reduction in amplitude). (c) Pattern visual evoked potential in hyperthyroidism (there is a moderate delay in latency with a statistically insignificant reduction in amplitude).

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There was an increase in the latencies in groups 1, 2, and 3 compared with group 4 (normal euthyroid patients) without a significant change in amplitudes ([Table 1] and [Figure 1] and [Figure 2]). [Table 1] shows no difference in amplitudes of FVEP and PVEP among groups, while there was a statistically significant difference in latencies among groups (amplitudes were measured in microvolt, and latencies were measured in ms).
Table 1 Visual evoked potential among groups

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[Figure 1]a shows FVEP in the normal patient (there is normal latency and amplitude). [Figure 1]b shows FVEP in hypothyroidism (there is a mild delay in latency with a statistically insignificant reduction in amplitude). [Figure 1]c shows FVEP in hyperthyroidism (there is a severe delay in latency with an insignificant reduction in amplitude). [Figure 2] illustrates PVEP in different groups. [Figure 2]a shows PVEP in a normal patient (there is normal latency and amplitude). [Figure 2]b shows PVEP in hypothyroidism (there is a mild delay in latency with an insignificant reduction in amplitude). [Figure 2]c shows PVEP in hyperthyroidism (there is a moderate delay in latency with insignificant change in amplitude).

In group 1, there was a statistically significant increase in latencies in recent cases more than in treated controlled hypothyroidism (P=0.009). There was an increase in latencies compared with group 4, but the differences were statistically insignificant (P=0.5; [Figure 3]).
Figure 3 Pattern visual evoked potential among groups.

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In group 2, there was a statistically significant increase in latency compared with group 4 (P=0.005). In addition, there was an increase in latencies in recent cases more than in treated controlled hypothyroidism (P=0.006).

In group 3, there was a statistically significant difference between recent untreated cases and treated controlled cases and between hyperthyroidism and group 4 (euthyroid cases, P=0.008 and 0.003, respectively).

In group 1 (subclinical hypothyroidism) in which there was an increase in TSH with normal T3 and T4, TSH was more than 10 μlU/ml, and free T4 and T3 were less than 0.6ng/dl) and 1.2pg/ml, respectively, in recent uncontrolled cases ([Table 2]).
Table 2 Hormonal assay among groups.

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In group 2 (overt hypothyroidism), there was a decrease in T3 and T4 with high TSH.

In group 3 (hyperthyroidism), there was an increase in T3 and T4 with low TSH.

In group 4 (euthyroid), there was normal TSH, T3, and T4.

In hyperthyroidism (group 3), there was proptosis in 29/70 (41.4%) patients, conjunctival injection in 24/70 (34.2%) patients and visual field defect in 2/70 (2.85%) patients. There were no cases with increased intraocular pressure, whether in primary or up gaze. Intraocular pressure was 12±4 mmHg (measured with Goldmann applanation tonometer). There was an increase in latencies in patients with proptosis and in patients with visual field defects than in patients without proptosis or visual field defects (P<0.002 and <0.0001, respectively; [Table 3] and [Table 4]).
Table 3 Relation of pattern visual evoked potential latencies and different eye signs in hyperthyroidism

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Table 4 Relation of pattern visual evoked potential latencies and different eye signs in hyperthyroidism.

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Correlation between PVEP and thyroid hormones ([Table 5]):
  1. In group 1, there was a weak insignificant correlation between P100 latencies and TSH, T3, and T4 (R=0.2, 0.01, and 0.04, P=0.3, 0.8, and 0.55, respectively).
  2. In group 2, there was a negative statistically significant correlation between p100 latencies and T3 and T4 (R=−0.45 and −0.5, P=0.009 and 0.04, respectively).
  3. In group 3, there was a positive moderate correlation between T3 and T4 and p100 latencies (R=0.55 and 0.64, P=0.01 and 0.02, respectively).
Table 5 Correlation between thyroid hormones and P100 latency

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  Discussion Top


Neurological affection in thyroid diseases is common. Hence, electrophysiological studies can be performed in thyroid patients to detect early nervous system involvement.

VEP is a reliable noninvasive measure of conduction along the optic pathway [5]. Abnormal VEP indicates delayed impulse conduction to the occipital cortex [6].

The P100 wave is caused by the activation of the primary visual cortex (the striate and peristriate cortex) and from the discharge of the thalamocortical fibers. The latency depends on myelination, while the amplitudes depend on the number of functioning axons in the nerve. Increased latency indicates myelination defects, whereas amplitude reduction is due to axonal dysfunction [7],[8].

In this study, in group 1 (subclinical hypothyroidism), there was an insignificantly prolonged latency. In uncontrolled untreated patients, there was an increase in latencies than in treated patients. The increase in latency was not correlated with thyroid hormones. In contrast, Jaiswal et al. [9] reported a higher latency thatcorrelated with TSH. They observed that the increase in TSH was associated with an increase in latency.

In group 2 (overt hypothyroidism), there was an increase in latency without a change in amplitude. Nezliel et al. [10] found a prolonged latency and a reduction in the amplitude in overt hypothyroidism. In addition, Sharma and Aggarwal [11] observed a reduction in amplitudes accompanied by prolonged latencies. Similarly, Velayutham and Kabali [3] reported a decrease in amplitudes and a delay in latencies in both eyes in hypothyroidism. In contrast, Khedr et al. [1] found a prolonged latency in P100 in only 52% of hypothyroid cases. Osterweil et al. [12] reported that P100 latency varied with check number. They found an increase in P100 latency only with the checks 20 not with the checks 50 (due to central retinal dysfunction).

In the present study, there was a statistically significant difference between subclinical and overt hypothyroidism in P100 latencies. However, Nazliel et al. [10] reported no difference between subclinical and overt hypothyroidism. The cause of a delay in the latency may be due to the central retinal dysfunction with hormonal disturbances causing demyelination.In group 3, there was proptosis in 41.4%, conjunctival injection in 34% and visual field defect in 2.8% of the patients. No patient had an abnormal optic nerve appearance in the clinical examination. All patients had prolonged latencies without a significant amplitude reduction in hyperthyroidism. Similarly, Salvi et al. [13] found a prolonged latency without a change in amplitude, while Thuangtong et al. [14] found a delay in latency and a decrease in amplitude in hyperthyroidism.

The mechanism of optic neuropathy in hyperthyroidism remains equivocal.

Enlarged extraocular muscles, fat crowding, ischemia due to increased retrobulbar pressure, mechanical stretch due to proptosis and perineural inflammation may be causes for optic neuropathy [15],[16],[17].


  Conclusion Top


An increased VEP latency may be an early sign of CNS affection in hypothyroidism and an early sign of optic neuropathy, especially in the presence of eye manifestation in hyperthyroidism.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Khedr EM, El Toony LF, Tarkhan MN, Abdella G. Peripheral and central nervous system alterations in hypothyroidism: electrophysiological findings. Neuropsychobiology 2000; 41:88–94.  Back to cited text no. 1
    
2.
Mishra UK, Kalita J. Clinical neurophysiology, 3rd edition. New Delhi: Elsevier 2014. pp. 283–296.  Back to cited text no. 2
    
3.
Velayutham G, Kabali B. Pattern reversal VEP in hypothyroid females. Natl J Basic Med Sci 2012; 2:365–368.  Back to cited text no. 3
    
4.
Odom JV, Bach M, Brigell M. ISCEV standard for clinical visual evoked potentials (2016 update). Doc Ophthalmol 2016; 133:1–9.  Back to cited text no. 4
    
5.
Phurailatpam J, Sharma AK, Singh R. Effect of age on pattern-reversal visual evoked potentials in Indian population. Int J Clin Exp Physiol 2014; 1:152–156.  Back to cited text no. 5
  [Full text]  
6.
Vedavathi KJ, Shekharappa KR, Venkatesh G. Reaction time study as a tool to identify central nervous system affect due to hypothyroidism. Int J Health Sci Res 2013; 3:29–32.  Back to cited text no. 6
    
7.
Kabbed G, Bhatt N, Litendra J, Prakash S. Electromyographic evaluation of blink reflex as a tool for early diagnosis of neurological dysfunction in patients of hypothyroidism. Ann Neurosci J 2013; 20:95–98.  Back to cited text no. 7
    
8.
Khadilkar SV. Neurological manifestations of thyroid and parathyroid disorders. New York, NY: WB Saunders 2010. pp. 609–612.  Back to cited text no. 8
    
9.
Jaiswal P, Saxena Y, Gupta R, Kaushik RM. Pattern reversal visual evoked potential and cognitive functions in subclinical hypothyroid subjects. J Neurosci Rural Pract 2016; 7:46–51.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Nazliel B, Akbay E, Irkeç C, Yetkin I, Ersoy R, Törüner F. Pattern visual evoked potential (PVEP) evaluation in hypothyroidism. J Endocrinol Invest 2002; 25:955–958.  Back to cited text no. 10
    
11.
Sharma AG, Aggarwal S. Visual evoked potentials in overt hypothyroid patients before and after achievement of euthyroidism. Indian J Endocrinol Metab 2017; 21:419–423.  Back to cited text no. 11
    
12.
Osterweil D, Syndulko K, Cohen SN, Pettler-Jennings PD, Hershman JM, Cummings JL. Cognitive function in non-demented older adults with hypothyroidism. J Am Geriatr Soc 1992; 40:325–335.  Back to cited text no. 12
    
13.
Salvi M, Spaggiari E, Neri F, Macaluso C, Gardini E. The study of visual evoked potentials in patients with thyroid-associated ophthalmopathy identifies asymptomatic optic nerve involvement. J Clin Endo Met 1997; 82:1027–1030.  Back to cited text no. 13
    
14.
Thuangtong A, Wangvarunyoo C, Kunavisarut T, Phithakphaosakul N. Visual evoked potentials (VEP) in Graves’ disease patients in Siriraj Hospital. Siriraj Med J 2013; 65:126–131.  Back to cited text no. 14
    
15.
Wiersinga WM, Kahaly G. Graves’ orbitopathy: a multidisciplinary approach − questions and answers, 2nd edition. Basel: Karger 2010. pp. 40–56.  Back to cited text no. 15
    
16.
Park KA, Kim YD, Woo K, Kee C, Han JC. Optical coherence tomography measurements in compressive optic neuropathy associated with dysthyroid orbitopathy. Graefes Arch Clin Exp Ophthalmol 2016; 254:1617–1624.  Back to cited text no. 16
    
17.
Iao WU, Rong SS, Ling AN, Brelen ME, Young AL, Chong KL. Electrophysiological studies in thyroid associated orbitopathy: a systematic review. Sci Rep 2017; 7:1–10.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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