|Year : 2019 | Volume
| Issue : 4 | Page : 294-298
Evaluation of visual evoked potential as a predictive marker for diabetic neuropathy
Sankha Subhra Chaudhuri1, Asim Kumar Dey1, Subhasis Jana1, Mousumi Bandyopadhyay1, Nabamita Chaudhury2, Sukanta Sen3
1 Department of Ophthalmology, Burdwan Medical College and Hospital, Bardhaman, West Bengal, Indaia
2 Department of Microbiology, Burdwan Medical College and Hospital, Bardhaman, West Bengal, Indaia
3 Department of Pharmacology, ICARE Institute of Medical Sciences and Research, Haldia, West Bengal, India
|Date of Submission||10-Sep-2019|
|Date of Decision||17-Sep-2019|
|Date of Acceptance||17-Oct-2019|
|Date of Web Publication||26-Dec-2019|
Dr. Asim Kumar Dey
Department of Ophthalmology, Burdwan Medical College and Hospital, Baburbag, P.O. Rajbati Bundwan, Bardhaman - 713 104, West Bengal
Source of Support: None, Conflict of Interest: None
Background: Diabetes mellitus causes neurodegeneration of retina before clinical symptoms and signs of diabetic retinopathy (DR), which may result in permanent visual loss. Hence, through neurodegenerative changes, we can predict and prevent DR well in advance. Aims and Objectives: To assess the neurodegenerative ocular morbidities among patients with diabetes before DR. Materials and Methods: This study included diabetic patients above the age of 40 years who have attended outpatient department of ophthalmology and diabetic clinic under the department of internal medicine in a tertiary care hospital in West Bengal and their age- and sex-matched control group from June 2017 to May 2018. All patients had gone through proper history taking, refraction, intraocular pressure measurement, external ocular examination, slit-lamp biomicroscopy, 90D examination, indirect ophthalmoscopy, and visual evoked potential (VEP). Results: The mean age of cases and controls was 56.87 and 57.29 years, respectively. Male and female percentage of cases and controls were 52.78 and 47.22 and 55.49 and 44.51, respectively. The percentage of Hindu and Muslim patients of cases and controls were 53.89 and 46.11 and 56.1 and 43.9, respectively. The mean P100 latency of the right and left eyes of cases was 108.61 and 107.63, whereas those of controls were 101.03 and 106.35, respectively. The mean P100 amplitude of the right and left eyes of cases was 5.68 and 5.69, whereas those of controls was 6.76 and 6.77, respectively. With respect to duration of diabetes, the mean P100 latency of the right and left eyes for <1 year, 1–2 years, and >2 years was 106.41 and 104.88, 112.19 and 112.15, and 108.38 and 107.31, respectively. With respect to duration of diabetes, the mean P100 amplitude of the right and left eyes for <1 year, 1–2 years, and 2 years was 5.42 and 5.68, 5.76 and 5.52, and 5.83 and 5.79, respectively. Conclusion: Our study shows that VEP changes occur in diabetes patients before the appearance of microaneurysm.
Keywords: Diabetes mellitus, diabetic retinopathy, neurodegeneration, visual evoked potential
|How to cite this article:|
Chaudhuri SS, Dey AK, Jana S, Bandyopadhyay M, Chaudhury N, Sen S. Evaluation of visual evoked potential as a predictive marker for diabetic neuropathy. TNOA J Ophthalmic Sci Res 2019;57:294-8
|How to cite this URL:|
Chaudhuri SS, Dey AK, Jana S, Bandyopadhyay M, Chaudhury N, Sen S. Evaluation of visual evoked potential as a predictive marker for diabetic neuropathy. TNOA J Ophthalmic Sci Res [serial online] 2019 [cited 2020 Jan 27];57:294-8. Available from: http://www.tnoajosr.com/text.asp?2019/57/4/294/273985
| Introduction|| |
Diabetes mellitus (DM) is a fast-reaching epidemic and globally accounts for about 425 million cases, projected to reach 642 million by 2040. There are over 72 million diabetes patients in India as of 2017 with the prevalence of 8.8 and progressing to reach a peg of 101.2 million by 2030. One among every three diabetic patients is affected with diabetic retinopathy (DR). Involvement of eyes in diabetes is a serious complication and may result in permanent visual loss. Diabetes can cause frequent change of refractive errors, early cataract formation, increased adnexal infective diseases, decrease in corneal sensation, corneal wearing out, and retinal vascular and neuropathic changes. Of these, DR is the most common and dreadful ocular complication of diabetes.
DR is a microvascular complication and is a leading cause of vision loss in middle-aged people in the world, especially who are in urban settings and economically active. More than 93 million people have eye complications due to diabetes, which is almost 1/3 of all the diabetics. Diabetes is a fast-progressing pandemic and so is DR.
Metabolic abnormalities due to diabetes cause peripheral and autonomic neuropathy. Recent views have suggested that central nervous system degeneration also occurs. DM involves both preganglionic and ganglionic elements in the retina and the macula. Thus, there is a growing interest on the involvement of central nervous system, rather than the peripheral nervous system. To do so, various electrophysiological tests have been implemented. Visual evoked potential (VEP) is an electrophysiological test, grossly working on the principle of electroencephalogram. It measures the electrical potential differences in the scalp in response to visual stimuli. From the WESDR to ETDRS to DRCR.net, scholars round the world have studied regarding the prevalence, progression, and treatment outcomes of various methods of DR. Yet, the neurodegenerative ocular changes associated with DM have been less talked about.
Our study is an endeavor to detect neurodegenerative retinal changes in diabetic patients using VEP to analyze the integrity of the visual pathway. It is, thus, an attempt to see retinal changes through neurodegeneration before clinical symptoms and signs and vascular abnormalities of the retina, so that we can predict and prevent DR well in advance. This is a first kind of study done in West Bengal.
Aims and Objectives
- To assess the prevalence of neurodegenerative ocular morbidities among patients with diabetes and nondiabetes as control with age and sex matching in a tertiary hospital in West Bengal
- To identify whether neurodegenerative changes or vasculopathic changes which is the earlier event in patients with diabetes.
| Materials and Methods|| |
The department of ophthalmology (outpatient department) and diabetic clinic of department of medicine in a tertiary care hospital in West Bengal.
All patients with diabetes attending the outpatient department of ophthalmology and the diabetic clinic under the department of internal medicine of a tertiary care hospital in West Bengal, meeting the inclusion and exclusion criteria, and their age- and sex-matched control groups were included.
Twelve months (June 2017–May 2018).
One hundred and eighty diabetic patients as cases (as per the American Diabetes Association criteria) and 164 cases with their age- and sex-matched control population.
Observational, analytical, case–control study.
Patients with DM above the age of 40 years and their age- and sex-matched controls who gave consent.
- Patients who have any type of retinal or choroidal diseases
- Patients who have any stage of DR
- Patients who are <40 years of age
- Patients with systemic neurodegenerative disorders such as dementia, Parkinson's disease, Alzheimer's disease, and mono- and polyneuropathies
- Patients with infectious diseases which cause neurodegeneration such as leprosy and neurotrophic viral keratitis
- Patients with neuropsychiatric disorders
- Patients with macular edema, any type of previous retinal detachment (macular laser photocoagulation, vitrectomy, intravitreal steroids, and/or antiangiogenic drugs), any intraocular surgery, refractive error >6D, previous diagnosis of glaucoma, uveitis, other retinal diseases
- Significant media opacities that precluded fundus examination or imaging
- Patients taking retinotoxic drugs such as hydroxychloroquine
- Pregnant patients
- Patients who refused to give valid informed consent.
All 184 diabetic patients as per the American Diabetes Association criteria (i.e., fasting blood sugar >=126mg/dl, OR postprandial blood sugar >=200 mg/dl, OR HbA1C >=6.5% OR, random blood sugar >=200 mg/dl in patients with symptoms of hypoglycaemia or hyperglycaemic crisis) and 164 healthy cases as with their age and sex matched control population were selected. They were subjected to detailed history history taking; refraction and intraocular pressure measurement; external ocular examination; anterior segment examination by slit-lamp biomicroscope; and detailed fundus examination by indirect ophthalmoscope and 90D lens and documenting it with fundus photography and VEP to study visual pathway integrity and to detect mechanical and neural abnormalities related to vision.
The RMS Aleron 401, 4-channel VEP machine was used. A montage consisting of one channel was used for VEP recording. Pattern-reversal stimulation was used. Stimulus rates were of 1–2 Hz. The electrode impedance was kept below 5 Ω. The signals recorded were filtered through a band spread of 2–100 Hz. Sweep speed was 30 ms/division and sensitivity 2 μV/Div. The sweep duration was maintained at 300 ms. Responses to 200 stimuli were amplified and averaged for each eye, which were then analyzed by inline computer having automated artifact rejection mechanism. The NPN complex waves were then identified with wave markers, and the values appear on tables. An amplification which ranged between 20,000 and 100,000 was used to record the VEP. A minimum of three records for each eye were obtained to ensure replicability of the VEP pattern.
Categorical variables were expressed as the number of patients and percentage of patients and compared across the groups using Pearson's Chi-square test for independence of attributes/Fisher's exact test as appropriate. Continuous variables were expressed as mean, median, and standard deviation (SD) and compared across the groups using Mann–Whitney U-test/Kruskal–Wallis test as appropriate. The statistical software SPSS (IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp., USA) was used for the analysis. An alpha level of 5% was taken, i.e., P < 0.05 was considered statistically significant.
Prior ethical approval of the institutional ethical committee was obtained for the study.
| Results|| |
The mean age of cases and controls was 56.87 and 57.29 years, respectively, which is not statistically significant (P = 0.964). Male and female percentage of cases and controls was 52.78 and 47.22 and 55.49 and 44.51, respectively, which is not statistically significant (P = 0.614). The percentage of Hindu and Muslim patients of cases and controls was 53.89 and 46.11 and 56.1 and 43.9, respectively, which is not statistically significant (P = 0.681).
The mean P100 latency of the right eye was 108.61 with standard deviation (SD) of 7.58 and that in the control group was 101.03 with SD of 4.31 [Table 1]. The mean P100 latency of the left eye in cases was 107.63 with SD of 12.49 and in the control group was 106.35 with SD of 7.47. This P100 latency was significantly (P< 0.001) increased in diabetic patients without retinopathy than in nondiabetic individuals. There was a reduction of N75-P100 amplitudes in these diabetic patients. The N75-P100 amplitude of the right eyes and left eyes was 5.68 ± 3.06 and 5.69 ± 3.15, respectively, in the case group. The amplitudes in the nondiabetic control group were 6.76 ± 1.54 and 6.77 ± 1.56, respectively, for both the eyes. This reduction of amplitudes was also significant (P< 0.001).
|Table 1: P100 latency and amplitude of cases (n=200) and control (n=164)|
Click here to view
With respect to duration of diabetes, the mean P100 latency of the right and left eyes for <1 year, 1–2 years, and >2 years was 106.41 ± 6.52 and 104.88 ± 13.43, 112.19 ± 7.01 and 112.15 ± 7.06, and 108.38 ± 7.98 and 107.31 ± 13.41, respectively, which is statistically significant (P< 0.001) [Table 2]. With respect to duration of diabetes, the mean P100 amplitude of the right and left eyes for <1 year, 1–2 years, and >2 years was 5.42 ± 3.14 and 5.68 ± 3.14, 5.76 ± 3.02 and 5.52 ± 3.13, and 5.83 ± 3.05 and 5.79 ± 3.21, respectively, which is not statistically significant (P = 0.764 and 0.962, respectively).
|Table 2: P100 latency and amplitude with respect to duration of diabetes (n=200)|
Click here to view
| Discussion|| |
Our results of prolongation of P100 latency and reduction of N75-P100 amplitudes are similar to the study by Heravian et al., who showed that the P100 wave latency was significantly longer in diabetic patients as compared to normal controls (P< 0.001); both diabetic patients without retinopathy and those with NPDR had significantly longer P100 latency than controls (P< 0.001 for both comparisons). There was a significant reduction in N75 (P = 0.037) and P100 (P = 0.001) amplitudes in diabetic patients.
Another study from India has also demonstrated prolongation of mean P100 latency and N75-P100 amplitude in diabetic patients compared to the controls (nondiabetics and age- and sex-matched people).
Algan et al. reported prolonged P100 latency in fifty DM patients, six of whom had DR. In 19 patients with Type II DM, they showed an increase in P100 latency. This result is almost like our result. Prolonged P100 latency of our study is also compatible with the reports of Mariani et al. They reported prolongation of P100 latency in 35 diabetic patients who did not have retinopathy. Ponte et al. reported prolongation of pattern VEP latencies in fifty asymptomatic insulin dependent diabetic patients without retinopathy. It is similar to our study, which shows prolongation in 180 patients without retinopathy.
Khatoon et al. found, in their study, that the mean value of amplitude of P100 among cases was 6.145 ± 0.79 and that of controls was 6.637 ± 0.81. Bivariate analysis showed that there was no significant difference in the amplitudes of P100 among cases and controls. Whereas, the bivariate analysis showed that the P100 latency was prolonged among cases than controls and there was a significant positive correlation between P100 latency and DM (P< 0.05). Their study result is almost compatible with the study result of ours, which shows that N75-P100 amplitude of the right and left eyes was 5.68 ± 3.06 and 5.69 ± 3.15, respectively, in the case group. The amplitudes in the nondiabetic control group were 6.76 ± 1.54 and 6.77 ± 1.56, respectively, in both the eyes.
Our study outcomes of statistically significant increase in P100 latency and reduction of N75-P100 amplitude are homogenous to the study of Gupta et al. They worked and pattern-reversal VEP was recorded in 116 patients (64 diabetics without retinopathy and 52 controls). P100 latency, N75-P100 amplitude, and interocular latency differences were compared between the diabetics and the controls. The study has demonstrated significant prolongation of mean P100 latency, reduction in N75-P100 amplitudes, and increased interocular latency difference in the diabetics as compared to the control group.
An old and famous study by Yaltkaya et al. including 25 diabetic patients has been studied to investigate the possible effects of the disease on the central nervous system by means of pattern shift VEPs. Patients with DR, glaucoma, and cataract were excluded from the study. The results obtained from a control group of 30 normal controls were compared to those of the patient group, in which sural nerve conduction velocities have also been determined to see whether there is a correlation between peripheral and central involvement of the nervous system. In diabetic patients, latency prolongation in the P100 and N140 components was observed. The N90-N140 interpeak latency was also prolonged. Our study also shows identical results.
Identical results of prolonged P100 latencies in VEP like our study are also seen in some other studies. Chopra et al. conducted a study on three groups (30 patients each) of Type 2 DM (different durations of disease) and one group of 30 healthy age- and sex-matched controls. Patients with reduced visual acuity which was not correctable with lenses or with retinopathy were excluded. The results showed significantly prolonged N70 and P100 latencies in diabetic patients and also a significant correlation between the delay in the P100 latency and the duration of the disease.
Raman et al. did a study on 25 diabetic patients and 15 age- and sex-matched controls. They included both noninsulin-dependent DM (NIDDM) and IDDM patients with a duration of diabetes <15 years. Patients with reduced visual acuity not correctable by glasses and those with DR were excluded from the study. P100 latencies and amplitudes as well as N75 latencies and amplitudes were recorded. The P100 latencies in diabetic patients were significantly prolonged with a mean ± SD of 107.32 ± 4.14 in diabetics and 102.5 ± 3.77 in controls (P = 0.001). The mean P100 amplitude was 7.64 ± 1.84 in diabetics with a control value of 8.03 ± 1.79 (P > 0.05).
Our study findings do corroborate with the delayed P100 latency, but not with the N75-P100 amplitude finding of the study by Verrotti et al. They showed that the P100 latency was significantly delayed in patients with diabetes compared with the control group (P< 0.01), whereas the N75-to-P100 amplitude was similar in both the groups. Pan CH conducted the PSVEP study on 46 cases of NIDDM and 13 cases of IDDM. The peak latency, interpeak latency, and evoked amplitude of P100 were analyzed in each case. For P100, amplitude was reduced as compared with the age-matched young control group. The interocular P100 (a positive component peaking around 100 milliseconds after the stimulus) latency difference was not statistically significant between the IDDM group and the age-matched control group. This finding is not compatible with our study results.
Limitation of study
The study population is small compared with the prevalence of diabetes and DR. As it was a cross-sectional study, the study population was examined only once. As a result, the course of the disease and the natural history of the effect due to the disease could not be studied. An undiagnosed case of neuropathy may have interfered with the VEP latency results.
| Conclusion|| |
DR is the most common and dreadful ocular complication of DM. There are more and more evidences coming out that retinopathy is not the first eye changes affecting the eye. It is the neurodegeneration of the retina and the VEP changes that occur before the appearance of microaneurysms. Our study also establishes this fact.
Patients with DM are overdiagnosed accidently. Hence, the process of diabetes and the complications arising from it are often set in when they are diagnosed. If no retinopathy sets in, as per the current early treatment diabetic retinopathy study (ETDRS) and united kingdom prospective diabetes study (UKPDS) study, annual examination of the eyes should be done. And, on every visit, VEP for P100 latency and N75-P100 amplitude should be measured to predict and prevent this dreadful DR well in advance.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]