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| ORIGINAL ARTICLE |
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| Year : 2016 | Volume
: 53
| Issue : 1 | Page : 28-32 |
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Multifocal electroretinogram in insulin dependent diabetes mellitus type I
Saly H Elkholy1, Zeinab El-Sanabary2, Mona M Nada1, Neveen M El-Fayoumy1, Amira Gohary1, Elham N Fayed1, Mohamed M Al-Kanishy3, Hossam Mohammed2
1 Department of Clinical Neurophysiology, Cairo University, Giza, Egypt
2 Department of Ophthalmology, Cairo University, Giza, Egypt
3 Department of Paediatric Diabetic Unit, Cairo University, Giza, Egypt
| Date of Submission | 03-Jul-2015 |
| Date of Acceptance | 18-Aug-2015 |
| Date of Web Publication | 15-Feb-2016 |
Correspondence Address:
Saly H Elkholy
MD, 15,106 Street, Maadi, 11431
Egypt
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1110-1083.176350
Background
Diabetic retinopathy (DR) is one of the leading causes of new blindness. The multifocal electroretinogram (mfERG) has been demonstrated to be useful in objective assessment of various retinal disorders.
Objective
To evaluate the retinal function by mfERG in adolescents with insulin dependent diabetes mellitus type 1 (IDDMT-1) without clinically evident DR.
Patients and methods
A case/control study carried out on 30 adolescents (30 eyes) with IDDMT-1 for 5 years' duration or more in comparison with 20 healthy adolescents (40 eyes). Cases with DR were excluded based on ophthalmological examination, slit-lamp biomicroscopy and fluorescein angiography. mfERG-P1 wave-peak time and amplitude were measured and expressed in the form of four quadrants and fovea.
Results
In diabetic adolescents, mfERG-P1 wave had small amplitude in the four examined quadrants. The foveal response was small in amplitude and delayed in time as well. There is a significant negative linear correlation between the ages of the diabetic adolescents, the duration of illness, the glycosylated hemoglobin level and the amplitude of mfERG-P1 wave in the upper nasal quadrant only.
Conclusion
Homogeneous reduction of the amplitude of the mfERG test in IDDMT-1 goes with the diffuse nature of the microvascular affection of the retina even before the retinopathy becomes clinically evident. Keywords: Adolescents, amplitude, diabetes mellitus, insulin dependent diabetes mellitus type 1, multifocal electroretinogram
How to cite this article:
Elkholy SH, El-Sanabary Z, Nada MM, El-Fayoumy NM, Gohary A, Fayed EN, Al-Kanishy MM, Mohammed H. Multifocal electroretinogram in insulin dependent diabetes mellitus type I. Egypt J Neurol Psychiatry Neurosurg 2016;53:28-32 |
How to cite this URL:
Elkholy SH, El-Sanabary Z, Nada MM, El-Fayoumy NM, Gohary A, Fayed EN, Al-Kanishy MM, Mohammed H. Multifocal electroretinogram in insulin dependent diabetes mellitus type I. Egypt J Neurol Psychiatry Neurosurg [serial online] 2016 [cited 2023 Nov 29];53:28-32. Available from: http://www.ejnpn.eg.net/text.asp?2016/53/1/28/176350 |
| Introduction | |  |
Insulin dependent diabetes mellitus type 1 (IDDMT-1) has an increasing worldwide incidence to be around 3% and about 78 000 children under age of 15 years develop IDDMT-1 worldwide [1]. In Egypt, the incidence is about 8/100 000 per year in children less than 15 years [2]. Diabetic retinopathy (DR) is one of the leading causes of new blindness. Its prevalence depends more on the duration of the disease rather than the patient's age. The functional abnormality within the retina in diabetes is caused by a variety of factors that lead to changes in one or more of the biochemical pathways or alternatively, hyperglycemia-induced changes in glial cell function [3]. It is a disease of small retinal vessels that are rarely encountered among diabetic children before puberty [4]. An Egyptian study revealed that 4.1% of patients developed DR, 23.07% of whom developed the retinopathy more than 10 years after diagnosis while 76.93% developed it in less than 10 years after diagnosis [2].
The multifocal electroretinogram (mfERG) has been demonstrated to be useful in objective assessment of various retinal disorders [5]. The mfERG reveals local retinal dysfunction - as local response delays - in diabetic eyes even before retinopathy. The location of dysfunction in the retina can be indicative of its future potential impact on vision [6].
| Aim of work | | |
To evaluate the retinal function by mfERG in adolescents with IDDMT-1 without clinically evident DR.
| Patients and methods | | |
Patients
This study is a case-control study that included 30 adolescents (30 examined eyes): 15 males and 15 females - with IDDMT-1 for 5 years' duration or more compared with 20 normal adolescents (40 examined eyes) - 10 males and 10 females. Those adolescents were recruited from the Diabetes Endocrine and Metabolism Pediatric Unit (DEMPU); Abou Elreesh Hospital, Cairo University to have stable hemoglobin A 1c (HbA 1c ) percentage in the last year. Cases with any DR were excluded based on ophthalmological examination, slit-lamp biomicroscopy and fluorescein angiography. The study had received the approval of the Faculty of Medicine, Cairo University research ethical committee in November 2013. For all participants, informed written consent was signed by the adolescent's parent or guardian after full explanation of the methodology and aim of the study.
Methods
Information regarding the date of onset, medication, controlled status, and glycosylated hemoglobin levels in blood (HbA 1c % normal value<5.3%) was verified by reviewing the patients' medical records. Information about puberty was asked upon but no attention was given to the menstrual cycle in relation to the timing of the tests.
The mfERG examinations using the Reti-Scan 21 (Roland Consult, Brandenburg a.d. Havel, Germany) were carried on the Ophthalmic Diagnostic and Laser Unit Cairo University Hospitals. We chose the eye with the better 'best corrected visual acuity' using Snellen chart to be examined in each diabetic patient with a total of 30 examined eyes. The visual acuity of the control cases chose not to be less than 6/9 and both eyes were examined simultaneously with a total of 40 eyes.
mfERG technique
According to International Society for Clinical Electrophysiology of Vision (ISCEV) standards 2011 [7], the recording electrode was HK loop electrode placed over the lower eye lid after 10 min of light adaptation and dilatation of the pupil - not less than 7 mm - with tropicamide hydrochloride 1%. The reference electrode was put on the ipsilateral temple. The ground electrode was placed on the forehead. The impedance was kept below 5 K Ohm. The adolescent was instructed to concentrate his/her eye on a red cross in the center of the stimulating screen. The stimulus consists of 61 hexagons, covering 25°-30° of the visual field and presented on a 20-inch monitor at a viewing distance of 33 cm. Each hexagon was temporally modulated between dark and light change with frame rate of 60 Hz and maximum luminance of 120 cd/m 2 . Each session lasted for 6 min with video monitoring fixation check. To improve fixation, each session was broken into 45 s to 1 min segment and six to eight trials were recorded in total. For each hexagon, peak to trough amplitude of P1 wave and its peak time were calculated. Average responses were calculated for the fovea (corresponding to hexagon number 31) and the four retinal quadrants [Figure 1]. | Figure 1: Multifocal electroretinogram shows the 61 segments, quadrants analysis as well as the fovea (area 31) and their color code; lower nasal (Q1-blue), upper nasal (Q2-red), upper temporal (Q3-green), lower temporal (Q4-orange) and fovea (F-olive).
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Abbreviation of quadrants used: Q1, lower nasal; Q2, upper nasal; Q3, upper temporal; Q4, lower temporal; and F, fovea.
Statistical methods
The data were coded and entered using the statistical package SPSS, version 15 (USA). The data were summarized using descriptive statistics: mean, SD, minimal and maximum values for quantitative variables and number. Statistical differences between groups were tested using independent sample t-test for quantitative normally distributed variables while nonparametric Mann-Whitney test was used for quantitative variables, which are not normally distributed. Correlations were done to test for linear relations between variables. P-values equal to or less than 0.05 were considered significant.
| Results | | |
The age of patients ranged from 10 to 17 years with a mean age of 13+2.16 years with no significant difference as compared with the healthy control group. The duration of illness ranged between 7 and 12 years with a mean of 9.23 ± 1.35 years. Their HbA 1c level ranged from 6.2 to 8.3% with a mean of 7.2 ± 0.51%. The average duration between HbA 1c measurement and multifocal testing was 1 month.
mfERG data were studied for minimum, maximum, mean and SD of the peak time (ms) and amplitude (μV/deg 2 ) of the four quadrants and fovea [Table 1]. The diabetic adolescents had smaller amplitude of the four quadrants' responses. The foveal response was small in amplitude and delayed in time as well [Figure 2]. | Figure 2: Multifocal electroretinogra m-P1 wave-amplitude; minimum, maximum, mean (black squares) and SD in the four quadrants of the retina and fovea (F) for the control group and the adolescents with insulin dependent diabetes mellitus type 1.
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 | Table 1: Multifocal electroretinogram-P1 wave-peak time (ms) and amplitude (nV/deg2) for the four quadrants and fovea
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There was a significant negative correlation between the ages of the diabetic adolescents, the duration of illness, the HbA 1c level and the amplitude of mfERG-P1 wave - in the upper nasal quadrant (Q2). The correlation coefficient (r) were −0.315, −0.320, and −0.258 and the P-values were 0.014, 0.012 and 0.047 respectively [Figure 3],[Figure 4] and [Figure 5]. Regarding the peak time, no correlation could be detected. | Figure 3: Linear negative correlation between multifocal electroretinogram (mfERG)-P1 wave-amplitude in the upper nasal quadrant (Q2) and the age of diabetic patient. The P-value was 0. 014.
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 | Figure 4: Linear negative correlation between multifocal electroretinogram (mfERG)-P1 wave-amplitude in the upper nasal quadrant (Q2) and the duration of illness. The P-value was 0. 012.
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 | Figure 5: Linear negative correlation between multifocal electroretinogram-P1 wave-amplitude in the upper nasal quadrant (Q2) and the HbA1c level. The P-value was 0.047. HbA1c, glycated hemoglobin; mfERG, multifocal electroretinog ram.
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| Discussion | | |
The potential hazards of diabetes mellitus on the visual function represent a huge medical problem worldwide. Its effect on the quality of life needs early detection of DR. Early before either the appearance of visible fundus lesions or retinal vasculature obvious changes, there is pericyte apoptosis and basement membrane thickening in cellular capillaries. Later, edema results from the breakdown of the inner blood retinal barrier and leakage of plasma constituents into the middle retinal layers, which could be focal or diffuse [8].
Standard normative data base for mfERG tests in adolescents (10-15 years) were not yet tested before. Even for adults, ISCEV recommended each lab to establish its normal control base, contributed the reason to the variations in recording equipment and the parameters, which make the use of data from other sources inappropriate. In this work, we tried to apply the same technical consideration recommended for adults to our teenage adolescents for easier comparison between publishing works.
The amplitude of the mfERG-P1 wave showed significant reduction in our adolescent IDDMT-1 patients without DR in the four quadrants and the fovea. This homogeneous reduction of the amplitude goes with the diffuse nature of the microvascular affection of the retina. Despite the lack of published articles discussing the impact of diabetes mellitus type 1 in mfERG in this particular age group to compare with, reduction of the P1 wave-amplitude was the most encountered results of the mfERG in diabetic type 2 patients without DR [9, 10, 11]. Our patients had delayed peak time only for the foveal response; however, implicit time prolongation was detected by Bearse et al. [6] and Han et al. [12] as the main predictive parameter for the development of DR. Elnahri et al. [13] mentioned the implicit time in the lower temporal quadrant as a promising predictor for the development of DR in Egyptian adults with diabetic type 2 patients, the amplitude of the foveal response was statistically smaller than their control. They also found the peak time of the foveal response to be delayed than the other quadrants but not in comparison with the control.
In early diabetes, the photoreceptor layers are not yet affected and the dysfunction is limited to the microvasculature supplying the inner retinal layers leading to ischemia and axonal damage, which is the first to be affected before the outer layers. In such condition amplitude reduction of the mfERG responses is reasonably encountered. With long duration of the disease, the underlying biochemical changes associated with hyperglycemia, for example, increased protein kinase C isomer, accumulation of advanced glycation end products, vitamin D deficiency, increased glucose sorbitol conversion or oxidative stress may be associated with different patterns of mfERG affection.
The age of the patient, the duration of diabetes and the HbA 1c level were negatively correlated with the mfERG amplitude in the upper nasal quadrant only . Elnahri et al. [13] demonstrated a positive linear correlation between the duration of illness and the peak time in the same quadrant (upper nasal). Although the duration of diabetes has implicated a strong risk factor for DR, it was not found to be significantly associated with neuroretinal function in Lakhani et al. [14]. Klemp et al. [5] demonstrated a correlation between HbA 1c and mfERG implicit times in adults DMT1 without DR; however, strict glycemic control in early stages will reduce the amount of defect detected [14]. Higher levels of HbA 1c in uncontrolled diabetes will affect the peak time and amplitude of the P1 wave [15] and will be more obvious with further advancing of age as after a sufficient duration of the disease, the retina is compromised to a severe delay of the peak time of the mfERG [16].
| Conclusion | | |
Homogeneous reduction of the amplitude of mfERG test in IDDMT-1 agrees with the diffuse nature of the microvascular affection of the retina.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | International Diabetes Federation. 6th ed.; 2014 update. Available at: http://www.idf.org/diabetesatlas. Accessed 3 February 2015.  |
| 2. | Ismail NA, Kasem OM, Abou-El-Asrar M, El-Samahy MH. Epidemiology and management of type 1 diabetes mellitus at the Ain Shams University Pediatric Hospital. J Egypt Public Health Assoc 2008; 83 :107-132. |
| 3. | Schneck ME, Bearse MA, Han Y, Barez S, Jacobsen C, Adams AJ. Comparison of mfERG waveform components and implicit time measurement techniques for detecting functional changes in early diabetic eye disease. Doc Ophthalmol 2004; 108 :223-230. |
| 4. | Rudolph CD, Rudolph AM, Hostetter MK, Lister G, Siegel NJ. Diabetes mellitus. Rudolph′s paediatric. 21st ed. New York: McGraw Hill Medical; 2003: 875-876. |
| 5. | Klemp K, Sander B, Brockhoff PB, Vaag A, Lund-Andersen H, Larsen M. The multifocal ERG in diabetic patients without retinopathy during euglycemic clamping. Invest Ophthalmol Vis Sci 2005; 46 :2620-2626. |
| 6. | Bearse MA Jr, Adams AJ, Han Y, Schneck ME, Ng J, Bronson-Castain K, Barez S. A multifocal electroretinogram model predicting the development of diabetic retinopathy. Prog Retin Eye Res 2006; 25 :425-448. |
| 7. | Hood DC, Bach M, Brigell M, Keating D, Kondo M, Lyons JS, et al. International Society for Clinical Electrophysiology of Vision. ISCEV standard for clinical multifocal electroretinography (mfERG) (2011 edition). Doc Ophthalmol 2012; 124 :1-13. |
| 8. | Curtis TM, Gardiner TA, Stitt AW. Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis?. Eye (Lond) 2009; 23 :1496-1508. |
| 9. | Adhikari P, Marasini S, Sah RP, Joshi SN, Shrestha JK. Multifocal electroretinogram responses in Nepalese diabetic patients without retinopathy. Doc Ophthalmol 2014; 129 :39-46. |
| 10. | Abdelkader M. Multifocal electroretinography in diabetic subjects. Saudi J Ophthalmol 2013; 27 :87-96. |
| 11. | Hood DC, Zhang X, Greenstein VC, Kangovi S, Odel JG, Liebmann JM, Ritch R. An interocular comparison of the multifocal VEP: a possible technique for detecting local damage to the optic nerve. Invest Ophthalmol Vis Sci 2000; 41 :1580-1587. |
| 12. | Han Y, Bearse MA Jr, Schneck ME, Barez S, Jacobsen CH, Adams AJ. Multifocal electroretinogram delays predict sites of subsequent diabetic retinopathy. Invest Ophthalmol Vis Sci 2004; 45 :948-954. |
| 13. | Elnahri GA, ElSanabary ZS, El Gohary AM, Ismaiel GA. A study of the preclinical stages of diabetic retinopathy using multifocal electroretinography. Egypt J Neurol Psychiat Neurosurg 2014; 51 :255-263. |
| 14. | Lakhani E, Wright T, Abdolell M, Westall C. Multifocal ERG defects associated with insufficient long-term glycemic control in adolescents with type 1 diabetes. Invest Ophthalmol Vis Sci 2010; 51 :5297-5303. |
| 15. | Holm K, Larsson J, Lövestam-Adrian M. In diabetic retinopathy, foveal thickness of 300 mum seems to correlate with functionally significant loss of vision. Doc Ophthalmol 2007; 114 :117-124. |
| 16. | Bronson-Castain KW, Bearse MA Jr, Han Y, Schneck ME, Barez S, Adams AJ. Association between multifocal ERG implicit time delay and adaptation in patients with diabetes. Invest Ophthalmol Vis Sci 2007; 4 :5250-5256. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1]
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