|Year : 2020 | Volume
| Issue : 1 | Page : 35-42
Multifocal electroretinogram changes in patients with retinal vein occlusion
Heba M Shafik, Amin E Nawar
Department of Ophthalmology, Faculty of Medicine, Tanta University, Tanta, Egypt
|Date of Submission||16-May-2019|
|Date of Decision||07-Nov-2019|
|Date of Acceptance||26-Nov-2019|
|Date of Web Publication||28-Feb-2020|
Heba M Shafik
Department of Ophthalmology, Tanta University, El Nadi Street, Kasr El Nadi Building, In Front of Zahran Market, 8th Floor, Tanta 31516
Source of Support: None, Conflict of Interest: None
Background Retinal vein occlusion (RVO) is one of the most common vascular retinal disorders that lead to macular edema. There is often discrepancy between visual prognosis and optical coherence tomography (OCT) changes. Multifocal electroretinogram (mfERG) provides useful information about retinal function in affected parts of the retina in patients with RVO.
Purpose The aim of this study was to assess the functional changes in patients with RVO by mfERG and to correlate these changes with OCT findings in those patients.
Patients and methods This is a prospective study of 30 eyes of patients with RVO, with their fellow eyes being taken as control. Thirteen eyes with central RVO, 12 eyes with branch RVO, and five eyes with hemi-RVO were included in the study. OCT to measure the central macular thickness was done in all patients. mfERG was also done in all patients. P wave amplitude and p wave implicit times were measured in the central area and all quadrants.
Results mfERG responses were markedly affected in all quadrants in central RVO, in the affected quadrants in branch RVO, and in the affected hemiretina in hemi-RVO. The differences between the p amplitude and p implicit time between the affected eyes and the fellow eyes were statistically significant in all patients. There was a significant correlation between the central macular thickness and p amplitude in the affected half of the retina in hemi-RVO.
Conclusion mfERG is a sensitive tool for assessment of retinal function in patients with RVO. mfERG can assess local retinal dysfunction in patients with RVO, which is sensitive to morphological changes detected by OCT.
Keywords: branch retinal vein occlusion, central retinal vein occlusion, fluorescein angiography, hemiretinal vein occlusion, multifocal electroretinogram, optical coherence tomography
|How to cite this article:|
Shafik HM, Nawar AE. Multifocal electroretinogram changes in patients with retinal vein occlusion. Delta J Ophthalmol 2020;21:35-42
|How to cite this URL:|
Shafik HM, Nawar AE. Multifocal electroretinogram changes in patients with retinal vein occlusion. Delta J Ophthalmol [serial online] 2020 [cited 2020 Apr 6];21:35-42. Available from: http://www.djo.eg.net/text.asp?2020/21/1/35/279717
| Introduction|| |
Retinal vein occlusion (RVO) is one of the commonest vascular diseases of the retina. Ischemic central retinal vein occlusion (CRVO) can lead to macular edema and severe visual loss ,. Variable degrees of ischemia and capillary nonperfusion can occur ,. Although baseline visual acuity is a strong predictor of final vision, visual improvement does not differ significantly between ischemic and nonischemic types ,.
Optical coherence tomography (OCT) assesses retinal thickness and morphology in RVO with macular edema, but there is often discrepancy between OCT findings and visual prognosis ,,. Multifocal electroretinogram (mfERG) is an objective, reproducible measure of inner retinal function ,. It is less time consuming and better tolerated than standard ERG .
In this study, the functional and anatomical changes in patients with RVO were correlated by mfERG and OCT, which can give a clue for prediction of prognosis.
| Patients and methods|| |
This is a prospective study that included 30 patients with RVO, comprising 13 patients with CRVO, 12 patients with branch retinal vein occlusion (BRVO), and five patients with hemi-RVO. The study was performed in Tanta University Eye Hospital in the period from January 2018 till January 2019 after taking patient’s approval by a signed written informed consent form for the investigations as a noninvasive maneuver for diagnosis. Patients also signed a written informed consent form to participate in the research and for publication of data without any mention of their identities. The study was approved by the Ethical committee of Tanta University and was consistent with the Helsinki declaration of 1975.
Patients with recent-onset RVO of less than 2-month duration were included. We excluded patients with previous intraocular surgery (including cataract extraction) within 6 months before diagnosis, diabetic retinopathy, and coincident retinal pathology, such as choroidal neovascular membrane and age-related macular degeneration. Moreover, patients with previous laser photocoagulation, intravitreal injection of triamcinolone acetonide or anti-vascular endothelial growth factor agents, and patients with prior ocular inflammation or retinal degeneration or neovascularization were excluded.
All patients underwent ophthalmic evaluation including measurement of best corrected visual acuity using illiterate E chart, which was converted to log MAR for statistical analysis; anterior segment examination using slit lamp; intraocular pressure measurement using applanation tonometry; and posterior segment examination using slit lamp biomicroscopy and indirect ophthalmoscopy.
At presentation, all patients did fundus fluorescein angiography by Topcon fundus camera 3D OCT-2000 (Topcon, Itabashi-Ku, Tokyo, Japan). In addition, OCT was done by Spectralis spectral domain OCT machine (Heidelberg Engineering, Heidelberg, Germany). mfERG was done by Retimax device (CSO, Pisa, Italy). mfERG responses were recorded simultaneously from both eyes.
The first-order mfERG response, namely, the P1 amplitude and P1 latency, were analyzed. The P1 amplitude was measured from the most negative trough of the waveform to the most positive peak of mfERG waveform. The P1 latency was defined as the time taken from the onset of the stimulus to reach the most positive peak of the waveform. Skin electrodes were attached lateral to the temporal canthi, and a reference electrode was attached to the glabellar region. HK-loop electrodes were placed in the lower fornix of each eye. The patient was seated 30 cm in front of a 61 hexagon array and maintained fixation on a central target with a screen luminance of 1500 cd/m2. The total mfERG recording time was 8 min broken into 30-s segments to facilitate good fixation. The patient’s fixation on the central target was observed throughout the test. The raw waveform was visible throughout the recording, and segments were rejected if there was saturation owing to excessive blinking or evidence of poor fixation. An appropriate pseudorandom binary m-sequence was used to control the 61 hexagonal elements. To analyze the 61 mfERG responses from each eye, the results were grouped into rings and quadrants. The P1 amplitude and P latency were grouped and averaged over the central ring and the four quadrants.
Data were analyzed using statistical package for social science (SPSS), version 17 (IBM Company, New York, New York, USA). c2 test of significance was used for comparison between groups. Spearman’s correlation coefficient was used to calculate the correlation between variables (P<0.05 was considered statistically significant; r≥0.5 indicated good correlation).
| Results|| |
The study included 13 patients with CRVO in one eye with cystoid macular edema. They comprised seven (53.8%) males and six (46.2%) females, with an age range of 45–65 years (mean±SD, 55.92±7.15 years). Ten patients were hypertensive, receiving antihypertensive medications, and five patients were diabetic, but no diabetic retinopathy changes were detected ([Table 1]). Regarding mfERG findings, it was found that the central p amplitude was decreased in CRVO eyes in comparison with the fellow eyes, and the central p implicit time was prolonged in CRVO eyes in comparison with the fellow eyes ([Figure 1]a–d), and the values were clinically significant ([Table 2]). In addition, there was a negative correlation between the central macular thickness and both the central p amplitude and the central p implicit time, but the results were statistically nonsignificant ([Table 3]). Five patients were ischemic by fluorescein angiography, whereas eight patients were not. The central p wave amplitude was decreased more in ischemic CRVO cases than nonischemic cases (P=0.011). In addition, the p wave implicit time was prolonged more in ischemic patients (P=0.002, [Table 4]).
|Figure 1 Fluorescein angiography, optical coherence tomography, and mfERG of a case of left central retinal vein occlusion and fellow eye. (a) Fluorescein angiography of affected eye. (b) OCT of affected eye showing macular edema and increased thickness. (c)mfERG trace array shows abnormal form and shape (the curve is full of irregularity). (d) Fellow eye in which N1 trough and P1 peak is present and clear. mfERG, multifocal electroretinogram; OCT, optical coherence tomography.|
Click here to view
|Table 2 Multifocal electroretinogram in the central area in eyes with central retinal vein occlusion and in fellow eyes|
Click here to view
|Table 3 The correlation between the central macular thickness and the central p amplitude and the central p implicit time in central retinal vein occlusion eyes|
Click here to view
|Table 4 The changes in p wave amplitude and implicit time in ischemic and nonischemic central retinal vein occlusion and branch retinal vein occlusion|
Click here to view
The study included five patients with hemi-RVO; all patients were hypertensive on medical treatment.
In these patients, it was found that the p amplitude was markedly reduced in the affected half of the retina compared with the unaffected half and with the fellow eye. In contrast, the p implicit time was greater in the affected half as compared with the unaffected half ([Figure 2]a–d) and fellow eye, and the values were statistically significant ([Table 5]).
|Figure 2 Fluorescein angiography, optical coherence tomography, and mfERG quadrant analysis of a case of left hemiretinal vein occlusion. (a) Fluorescein angiography. (b) OCT showing cystoid macular edema of left eye. (c) mfERG trace array of left hemiretinal vein occlusion shows abnormal form and shape of waves in the affected hemiretina. (d) Quadrant analysis of the affected eye. mfERG, multifocal electroretinogram; OCT, optical coherence tomography.|
Click here to view
|Table 5 Multifocal electroretinogram in patients with hemiretinal vein occlusion|
Click here to view
In addition, it was found that there was a significant negative correlation between the central macular thickness and p amplitude ([Table 6]).
|Table 6 The correlation between the central macular thickness and the p amplitude and p implicit time in the affected half in hemiretinal vein occlusion patients|
Click here to view
As for BRVO, the study included 12 patients. All patients were hypertensive receiving antihypertensive medications. The p amplitude was less in the affected quadrant than the unaffected quadrants and the same quadrant in the fellow eyes. However, the implicit time was greater in the affected quadrant when compared with the unaffected quadrants and the fellow eyes ([Figure 3]a–d and [Figure 4]a, b), and the values were statistically significant ([Table 7]). Moreover, there was a negative correlation between the central macular thickness in the affected quadrant and the p amplitude in patients with BRVO, but it was statistically nonsignificant ([Table 8]). Four patients were ischemic by fluorescein angiography, whereas eight patients were not. The central p wave amplitude was decreased more in ischemic patients with BRVO than nonischemic patients (P=0.006). In addition, the p wave implicit time was prolonged more in ischemic patients (P=0.017, [Table 4]).
|Figure 3 Fluorescein angiography, optical coherence tomography, and mfERG quadrant analysis of a case of left upper temporal branch retinal vein occlusion. (a) Fluorescein angiography. (b) OCT showing macular edema. (c) Quadrant analysis of affected eye. (d) Fellow eye showing decreased p amplitude and delayed implicit time in the affected quadrant compared with the fellow eye. mfERG, multifocal electroretinogram; OCT, optical coherence tomography.|
Click here to view
|Figure 4 (a) mfERG trace array of left upper temporal branch retinal vein occlusion (same case of Fig. 3) shows abnormal form and shape of waves in the affected quadrant. (b) mfERG trace array of the fellow eye. mfERG, multifocal electroretinogram.|
Click here to view
|Table 7 Multifocal electroretinogram changes in the affected quadrant, unaffected quadrants and the fellow eyes in patients with branch retinal vein occlusion|
Click here to view
|Table 8 The correlation between the central macular thickness and the p amplitude and p implicit time in branch retinal vein occlusion patients|
Click here to view
On the contrary, in patients who showed photoreceptors disruption by OCT, there was a significant decrease in central p wave amplitude and more prolonged implicit time than other patients with no photoreceptors disruption ([Table 9]).
|Table 9 The differences in central p wave amplitude and implicit time in central retinal vein occlusion, branch retinal vein occlusion, and hemiretinal vein occlusion with and without photoreceptor disruption by optical coherence tomography|
Click here to view
| Discussion|| |
The present study evaluated different techniques for interpretation of retinal insult, both anatomically and functionally, in patients with RVO. The OCT was used to measure the thickness and morphological changes of the retina, whereas fluorescein angiography mainly gives information about the vascular status, to differentiate ischemic from nonischemic retina, as well as evaluation of the amount and site of the retinal leakage. mfERG, on contrary, gives us functional analysis that reflects the actual physiological changes of the retinal neurons.
The study was conducted on 13 eyes of 13 patients with CRVO. The first-order responses obtained from the 13 eyes with CRVO were significantly different from those derived from the fellow unaffected eyes. Moreover, the central p amplitudes were greatly reduced than that of the fellow eyes, whereas the central p implicit times were significantly prolonged. There was a negative correlation between mfERG p amplitudes and latencies in the affected eyes and central retinal thickness measured by OCT in the central area, but it was statistically insignificant. This finding is consistent with previous reports of mfERG response in patients with CRVO, in whom P amplitudes were reduced and implicit times were delayed in affected eyes ,,.
Five cases of hemi-RVO were included in this study. There was prolongation of implicit time of p wave of mfERG in the affected hemiretinae than in unaffected hemiretinae. In addition, the p amplitude was greatly reduced than that of the unaffected half of the retina. Moreover, the p amplitude was reduced and p implicit time was prolonged in affected hemiretinae in comparison with symmetrical half of retinae in the fellow eyes. These findings agree with Dolan and colleagues, who evaluated hemi-RVO using mfERG and compared the responses from affected hemiretina and unaffected hemiretina in each affected eye and also compared the responses from each affected hemiretina and the symmetrical hemiretina of each fellow eye. They found that mfERG p implicit time was greater in the affected hemiretina than that in the unaffected hemiretina, and p wave amplitude was reduced in affected eyes when compared with the fellow eyes .
In the 12 cases of BRVO, there was a delay in implicit time of p wave with subnormal amplitude in affected quadrants. This was similar to the findings of Ikeda et al. , who observed abnormal response amplitude in the affected quadrants and in the central area with delay in implicit times. In addition, Hvarfner et al.  found a significant difference in the mean amplitude (P=0.01) and latency (P=0.001) between the affected and nonaffected quadrants of the retina in the same eyes.
In general, there was a significant difference between the mfERG response of affected eyes in all subgroups and the unaffected eyes with RVO. In spite of that difference between affected and nonaffected fellow eyes, mfERG abnormalities were noted in the fellow eyes, which probably reflect abnormal retinal function in these patients owing to associated systemic diseases, such as hypertension (in 27 cases) and diabetes mellitus (in five cases). This was supported by previous ERG studies for patients with RVO, which found 36% of fellow eyes to have abnormal response ,. Moreover, comparing central macular thickness measured by OCT and mfERG p wave amplitudes and p wave implicit time, there was a significant negative correlation between p amplitudes in the affected eyes and central macular thickness measured by OCT in patients with hemi-RVO (P=0.010).
This is nearly similar to the studies of Ikeda et al. , who also found a significant correlation between foveal retinal thickness and mfERG P1 response density. On the contrary, Hvarfner et al.  reported nonsignificant correlation between mfERG and OCT finding, despite that macular ischemia measured by fluorescein angiography correlated well with prolonged implicit time of mfERG. Therefore, it is likely that mfERG reflects more of nonlinear processes in the retina that is potentially affected by retinal ischemia owing to changes in adaptive mechanisms of the retina secondary to the underlying disease caused by the vein occlusion. Most studies agree that RVO causes ERG abnormalities and that highly abnormal ERG is associated with a poorer prognosis ,.
| Conclusion|| |
RVO affected mfERG amplitude and implicit time. The site of amplitude reduction and implicit time delay vary according to the area of RVO and is more pronounced in ischemic than nonischemic cases. The degree of amplitude reduction and implicit time delay increases as the severity of RVO increases, which is an indicator of poorer prognosis, especially in cases with photoreceptor disruption by OCT. OCT and mfERG provide anatomical and functional assessment of the retina in RVO.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Quinlan PM, Elman MJ, Bhatt AK, Mardesich P, Enger C. The natural course of central retinal vein occlusion. Am J Ophthalmol 1990; 110:118–123.
Glacet-Bernard A, Kuhn D, Vine AK, Oubraham H, Coscas G, Soubrane G. Treatment of recent onset central retinal vein occlusion with intravitreal tissue plasminogen activator: a pilot study. Br J Ophthalmol 2000; 84:609–613.
Beak SU, Kwon SI, Park IW, Choi KJ. Consecutive macular edema and visual outcome in branch retinal vein occlusion, J Ophthalmol 2014; ID 439483:6.
Hood DC. Assessing retinal function with multifocal technique. Prog Retinal Eye Res 2000; 19:607–616.
The Central Vein Occlusion Study Group. Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol 1997; 115:486–491.
Hayreh SS, Zimmerman MB. Branch retinal vein occlusion: natural history and visual outcome. JAMA Ophthalmol 2014; 123:13–22.
Hayreh SS, Zimmerman MB. Fundus changes in central retinal vein occlusion. Retina 2015; 35:29–42.
Martínez-Jardón CS, Meza-de Regil A, Dalma-Weiszhausz J, Leizaola-Fernandez C, Morales-Canton V, Guerrero-Naranjo JL et al.
Radial optic neurotomy for ischaemic central vein occlusion. Br J Ophthalmol 2005; 89:558–561.
Kumagai K, Furukawa M, Ogino N, Uemura A, Larson E. Long-term outcomes of vitrectomy with or without arteriovenous sheathotomy in branch retinal vein occlusion. Retina 2007; 27:49–54.
Ilginis T, Clarke J, Patel PJ. Ophthalmic imaging, Br Med Bulletin 2014; 111:77–88.
Seeliger MW, Kretschmann UH, Apfelstedt-Sylla E, Zrenner E. Implicit time topography of multifocal electroretinograms. Invest Ophthalmol Vis Sci 1998; 39:718–723.
Hood DC, Frishman LJ, Saszik S, Viswanathan S. Retinal origins of the primate multifocal ERG: implications for the human response. Invest Ophthalmol Vis Sci 2002; 43:1673–1685.
Dolan FM, Parks S, Keating D, Dutton GN, Evans AL. Multifocal electroretinographic features of central retinal vein occlusion. Invest Ophthalmol Vis Sci 2003; 44:4954–4959.
Hasegawa S, Ohshima A, Hayakawa Y, Takagi M, Abe H. Multifocal electroretinograms in patients with branch retinal artery occlusion. Invest Ophthalmol Vis Sci 2001; 42:298–304.
Moschos MM, Moschos M. Intraocular bevacizumab for macular edema due to CRVO. A multifocal-ERG and OCT study. Doc Ophthalmol 2008; 116:147–152.
Dolan FM, Parks S, Keating D. Wide field multifocal and standard full field electroretinographic features of hemiretinal vein occlus. DOC Ophthalmol 2006; 112:43–52.
IKeda J, Hasegawa S, Suzuki K. Evaluation of macula in patients with branch retinal vein occlusion using multifocal electroretinogram and optical coherence tomography. Nippon Ganka Zasshi 2005; 109:142–147.
Hvarfner C, Andreasson S, Larsson J. Multifocal electroretinogram in branch retinal vein occlusion. Am J Ophthalmol 2003; 136:1163–1165.
Johnson MA, Marcus S, Elman MJ. Neovascularization in central retinal vein occlusion. Electroretinographic findings. Arch Ophthalmol 1988; 106:348–352.
Morrell AJ, Thompson DA, Gibson JM. Electroretinography as a prognostic indicator of neovascularization in CRVO. Eye 1991; 5:362–368.
IKeda J, Hasegawa S, Suzuki K. Multifocal electroretinograms in patients with retinal vein occlusion. Nippon Ganka Gakkai Zasshi 2004; 108:84–91.
Larsson J, Andreasson S. Photopic 30Hz flicker ERG as a predictor for rubeosis in central retinal vein occlusion. Br J Ophthalmol 2001; 85:683–685.
Yasuda S, Kachi S, Kondo M. Significant correlation between electroretinogram parameters and ocular vascular endothelial growth factor concentration in central retinal vein occlusion eyes. Invest Ophthalmol Vis Sci 2011; 52:5737–5742.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]