Oscillatory potential findings in patients with acute ischaemic central retinal vein occlusion

Abstract

Aims

To explore the sensitive components of full-field electroretinography (ERG) as indicators of retina function at the onset of acute ischaemic central retinal vein occlusion (CRVO).

Methods

11 patients (11 eyes) with ischaemic CRVO and 32 patients (32 eyes) with non-ischaemic CRVO who presented with first-episode unilateral CRVO within 1 month of symptom onset and with no previous intervention were examined by the International Society for Clinical Electrophysiology of Vision standard ERG.

Results

A significant amplitude decline and peak time delay in light-adapted (LA) 3 ERG and LA 30 Hz flicker ERG (p<0.05 for all) was found in the ischaemic CRVO eyes, compared with the non-ischaemic CRVO eyes. The b/a amplitude ratio of dark-adapted (DA) 3 ERG, DA 10 ERG and LA 3 ERG was significantly different between the ischaemic and non-ischaemic groups (p<0.05 for all). Regarding oscillatory potentials (OPs), the amplitudes of OP1, OP2 and OP3 as well as the sum of DA 3 OP1–4 amplitudes (∑OPs) showed significant changes (p<0.01 for all) between two groups. No peak time delay of OPs was found between the ischaemic and non-ischaemic CRVO eyes.

Conclusion

The amplitude of DA 0.01 ERG, components of LA 3 ERG and LA 30 Hz flicker ERG, and the b/a amplitude ratio could be among the most sensitive indicators in patients with acute ischaemic CRVO. The amplitudes of OP1, OP2, OP3 and ∑OPs in the CRVO eyes were reduced to 40% of the control values, showing that this quantitative method is reliable for detecting ischaemic retinal diseases, even in early stage.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• With previous ISCEV standard, full-field electroretinography (ERG) is an important technique to evaluate the ischemic state of retinas with a CRVO.

WHAT THIS STUDY ADDS

• With new ISCEV standard 2015＆2022, more detailed ERG components, especially the amplitudes of oscillatory potentials (OPs), could be the sensitive indicators for detecting ischemic CRVO.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• Results of this study may be a helpful practice guide for ERG testing in the diagnosis of ischemic CRVO. This information may assist ophthalmologists to evaluate the ischemic state of retina in CRVO, not only for the prognosis but also for the selection of treatment strategies.

Introduction

Central retinal vein occlusion (CRVO) is a common retinal vascular disorder. Although the exact aetiology of a CRVO has not been determined, it is important to evaluate the ischaemic state of retinas in CRVO for the prognosis and selection of treatment strategies.¹ Fundus fluorescein angiography (FFA) has been traditionally used to classify eyes with a CRVO into ischaemic and non-ischaemic types based on the extent of the capillary non-perfused areas.² The ‘ischemic CRVO’ was identified by the Central Retinal Vein Occlusion Study (CVOS) using an angiographic criterion of 10 disc areas or more of capillary non-perfusion on FFA, and functional tests (visual acuity, visual fields, relative afferent pupillary defect and electroretinography (ERG)) have demonstrated a high sensitivity and specificity for predicting ‘ischemic CRVO’.^{3 4}

Full-field ERG is an objective method of evaluating the retinal function by investigating the response of the entire retina, and could be a highly suitable method of identifying ocular ischaemia, especially when FFA is not feasible.^{5 6} Several studies have investigated which ERG parameter is most useful for monitoring ischaemic CRVO eyes,^{7 8} involving the cone a-wave, b-wave,^{2 9} 30 Hz flicker^{10 11} and photopic negative response (PhNR).^{9 12} However, there have been few reports comparing oscillatory potentials (OPs) between ischaemic and non-ischaemic CRVOs. The purpose of this study was to evaluate the electrophysiological status of eyes with ischaemic or non-ischaemic CRVO by ERG, and to determine the most sensitive ERG parameter for early identification of acute treatment-naive CRVO with the International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocol for clinical ERG.^{13 14} More sensitive and reliable components are needed in clinical practices to differentiate ischaemic from non-ischaemic CRVO in the acute stage.

Materials and methods

Study design

All patients underwent a detailed ophthalmological examination including measurements of the best corrected visual acuity, with a Snellen chart, slit-lamp biomicroscopy and indirect ophthalmoscopy at the initial visit and throughout the follow-up period. FFA and ERG were performed, and all CRVO eyes were classified as the ischaemic type or non-ischaemic type based on the findings of the FFA performed at the initial visit.

The inclusion criteria called for male or female patients with the first episode of ischaemic or non-ischaemic CRVO at the onset of acute CRVO (≤1 month). Their contralateral unaffected eyes were considered as the control group. The exclusion criteria included all those patients who previously had an episode of CRVO, those who were unable to cooperate for FFA or ERG recording and those who had other causes of vision loss (eg, diabetic retinopathy, high myopia, cataract, glaucoma or other severe eye disease).

Fluorescein angiography measurements

All CRVO eyes were classified as the ischaemic type or non-ischaemic type based on the findings of the FFA performed at the initial visit. An intravenous bolus injection of fluorescein sodium solution (2 mL of 25% solution) was given when performing the FFA. According to the CVOS, pictures of the central fundus and of the mid-periphery in all four quadrants were taken. The area of the optic disc was used as a reference area to evaluate the degree of ischaemia. CRVO was classified as the ischaemic type if the eye had at least a 10-disc area of retinal capillary non-perfusion within the area of a standard photographic field.¹⁵

Full-field ERG recordings

The amplitude of the a-wave was measured from the isoelectric line to the wave trough and the a-wave peak time was measured from the stimulus onset to the a-wave trough. The amplitude of the b-wave was measured from the a-wave trough to the wave peak and the b-wave peak time was measured from the stimulus onset to the b-wave peak.¹⁶

The ISCEV standard full-field ERGs assess generalised retinal function under dark-adapted (DA) and light-adapted (LA) conditions. The DA ERGs include responses to flash strengths (in photopic units; phot) of 0.01, 3 and 10 phot cd·s/m² (DA 0.01 ERG; DA 3 ERG; DA 10 ERG). The LA ERGs are to a flash strength of 3 phot cd·s/m², superimposed on a light-adapting background (luminance 30 cd/m²) as single flashes (LA 3 ERG) and at a frequency close to 30 Hz (LA 30 Hz ERG). Full-field ERG (Espion; Diagnosys, USA) was performed in accordance with the ISCEV standard 2015 and 2022.^{13 14} The ERG signals from both eyes of all the subjects were collected for six different stimuli, including four records in the darkness (DA 0.01, DA 3, DA 3 OPs and DA 10) and two records in brightness (LA 3 and LA 30 Hz flicker). Before recording, the pupils were dilated to at least 7 mm in diameter in all cases. Oxybuprocaine hydrochloride eye-drops (Santen Pharmaceutical) were used as topical anaesthesia, and a jet electrode was used as the corneal electrode.

OP calculation

DA 3 OP ERG was performed. Four main components of OPs have been described: OP1, OP2, OP3 and OP4. Two main parameters are derived from the OP, conventionally known as amplitude in microvolts (μV) and peak time in milliseconds (ms). The OP1 amplitude was measured from the baseline to the peak of the wave. The OP2, OP3 and OP4 amplitudes were measured from the trough of the preceding wave to the peak of the corresponding wave. Peak time denotes the time taken to reach the maximum amplitude of each wave. Additionally, the summed amplitude of the four OPs (∑OPs) was calculated for each eye.

Statistical analysis

All statistical analyses were performed with SPSS V.25.0 (SPSS). Continuous variables were described as means±SDs (${\displaystyle \overline{\mathrm{X}}\pm \mathrm{S}}$). When the data were normally distributed, a one-sample t-test was used. When the data were not normally distributed, the significance of each difference was assessed using the Mann-Whitney U test. A p≤0.05 was considered statistically significant.

Results

Clinical details

Between October 2016 and October 2020, a total of 43 patients (25 men and 18 women) with a mean±SD age of 54.3±16.4 years, with a range of 17–79 years, were retrospectively analysed in the study. Among the patients who presented with first-episode CRVO within 1 month of symptom onset and had not received any previous intervention, 11 eyes of 11 patients (9 men and 2 women, aged 67.0±9.7 years) had ischaemic CRVO, and 32 eyes of 32 patients (16 men and 16 women, aged 49.9±16.0 years) had non-ischaemic CRVO.

Electroretinographic findings

As the table 1 displays, eight waves of five stimuli (16 components), including the amplitude and peak time for each wave, were recorded. For the ischaemic CRVO group, 13 components from ischaemic CRVO eye showed significant changes in the amplitude or peak time of each stimulus from contralateral unaffected eyes (p<0.05 for all), while the following three components did not: the peak time of the b-wave of DA 10 ERG, the amplitude of the a-wave of DA 10 ERG and the amplitude of the a-wave of LA 3 ERG. For the non-ischaemic CRVO group, nine components from the CRVO eye were found to be significantly different from the values for contralateral unaffected eyes; importantly, the peak time of the response to each stimulus was significantly different between groups. Non-ischaemic CRVO had a little effect on the amplitude of each wave, except for the b-wave of DA 0.01 ERG.

Table 1. Summary of p values for the two-group comparisons in full-field electroretinogram findings of acute CRVO.

Parameter	CRVO eye versus unaffected eye in ischaemic CRVO group		CRVO eye versus unaffected eye in non-ischaemic CRVO group		Ischaemic versus non-ischaemic CRVO eye
	P value	Comparison	P value	Comparison	P value	Comparison
DA 0.01 ERG b-wave am (μV)	0.000	***	0.047	*	0.000	***
DA 0.01 ERG b-wave pt (ms)	0.034	*	0.029	*	0.296	****
DA 3 ERG a-wave am (μV)	0.030	*	0.440	****	0.008	**
DA 3 ERG a-wave pt (ms)	0.035	*	0.002	**	0.005	**
DA 3 ERG b-wave am (μV)	0.002	**	0.795	****	0.000	**
DA 3 ERG b-wave pt (ms)	0.001	***	0.000	***	0.253	****
DA 10 ERG a-wave am (μV)	0.229	****	0.722	****	0.068	****
DA 10 ERG a-wave pt (ms)	0.002	**	0.000	***	0.006	**
DA 10 ERG b-wave am (μV)	0.005	**	0.974	****	0.000	***
DA 10 ERG b-wave pt (ms)	0.413	****	0.006	**	0.884	****
LA 3 ERG a-wave am (μV)	0.108	****	0.167	****	0.001	***
LA 3 ERG a-wave pt (ms)	0.006	**	0.001	***	0.040	*
LA 3 ERG b-wave am (μV)	0.000	***	0.063	****	0.000	***
LA 3 ERG b-wave pt (ms)	0.000	***	0.000	***	0.000	***
LA 30 Hz flicker ERG am (μV)	0.000	**	0.087	****	0.000	***
LA 30 Hz flicker ERG pt (ms)	0.000	***	0.000	***	0.000	***

The significant differences between the groups are indicated as *p≤0.05, **p≤0.01, ***p≤0.001, ****p>0.05.

amamplitudeCRVOcentral retinal vein occlusionDAdark-adaptedERGelectroretinographyLAlight-adaptedOpsoscillatory potentialsptpeak time

Compared with the CRVO eyes in the non-ischaemic CRVO group, an amplitude decline and a peak time delay were found in the response to each stimulus by the CRVO eyes in the ischaemic CRVO group, especially DA 0.01 ERG, LA 3 ERG and LA 30 Hz flicker ERG (p<0.05 for all). The amplitude decline and peak time delay associated with ischaemic CRVO eyes were more significant than those associated with non-ischaemic CRVO eyes. The significant changes in amplitude were strongest in the b-wave of DA 0.01 ERG (p=0.000) in both ischaemic and non-ischaemic CRVO eyes, with both of these categories having significantly lower b-wave amplitude than the contralateral unaffected eyes; the decrease in ischaemic CRVO eyes was significantly greater than that in non-ischaemic CRVO eyes. ERG records from two patients with acute CRVO are shown in figure 1.

Figure 1. Full-field electroretinogram (ERG) recordings from two patients with acute central retinal vein occlusion (CRVO). (A1–A7) Fundus fluorescein angiography (FFA) and full-field ERG of a patient with non-ischaemic CRVO. Not all amplitudes and peak times of these six stimuli were changed in the non-ischaemic CRVO eye. For example, amplitudes of dark-adapted (DA) 0.01 ERG b-wave (A2), DA 3 ∑OPs (A4), light-adapted (LA) 3 ERG b-wave (A6) and LA 30 Hz flicker ERG (A7) were slightly reduced to 90.75%, 50.1%, 77.33% and 64.06%, respectively, compared with the unaffected eye. (B1–B7) FFA and ERG of a patient with ischaemic CRVO. The area of retinal angiographic non-perfusion was delineated by yellow line (B1). The amplitude decline and peak time delay of each stimulus were found in the ischaemic CRVO eye. For example, amplitudes of DA 0.01 ERG b-wave (B2), DA 3 ∑OPs (B4), LA 3 ERG b-wave (B6) and LA 30 Hz flicker ERG (B7) were dramatically reduced to 20.04%, 19.61%, 31.64% and 38.73%, respectively, compared with the unaffected eye. ∑OPs, sum of DA 3 OP1–4 amplitudes.

b/a amplitude ratio

For the ischaemic and non-ischaemic CRVO eyes, respectively, the b/a amplitude ratios were 1.34±0.52 and 2.31±0.83 for DA 3 ERG, 1.12±0.31 and 1.69±0.37 for DA 10 ERG and 1.66±0.42 and 3.13±0.85 for LA 3 ERG. For the ischaemic CRVO group, the b/a amplitude ratios of the DA 3, DA 10 and LA 3 ERG recordings were significantly lower than those of the contralateral unaffected eyes of the same group of subjects (p<0.05 for all), but such differences were not found in the non-ischaemic CRVO group. In addition, the b/a amplitude ratios of these three stimuli were statistically significant between the ischaemic CRVO eyes and the non-ischaemic CRVO eyes (p<0.05 for all) (table 2).

Table 2. b/a amplitude ratio of full-field electroretinogram in acute CRVO.

	Ischaemic CRVO group (n=11)			Non-ischaemic CRVO group (n=32)			Ischaemic versus non-ischaemic CRVO eye
	CRVO eye	Unaffected eye	P value	CRVO eye	Unaffected eye	P value	P value
b/a amplitude ratio of DA 3 ERG	1.34±0.52	1.9±0.41	0.011*	2.31±0.83	2.16±0.51	0.386	0.001**
b/a amplitude ratio of DA 10 ERG	1.12±0.31	1.65±0.36	0.001**	1.69±0.37	1.7±0.32	0.921	0.000**
b/a amplitude ratio of LA 3 ERG	1.66±0.42	3.23±0.68	0.000**	3.13±0.85	3.13±0.88	0.983	0.000**

The significant differences between the groups are indicated as *p≤0.05, **p≤0.001.

CRVOcentral retinal vein occlusionDAdark-adaptedERGelectroretinographyLAlight-adapted

OP results

The amplitude and peak time of OP1, OP2, OP3, OP4 and ∑OPs were individually evaluated (table 3). In the ischaemic CRVO eye group, the average amplitudes of OP1, OP2, OP3, OP4 and ∑OPs were 3.41±1.07, 8.31±3.30, 7.80±2.16, 2.90±1.39 and 22.38±7.01 μV, respectively, which decreased to 22.7%, 21.2%, 37.8%, 33.6% and 26.2% of those of the unaffected eyes; the amplitudes of OP1 (p=0.000), OP2 (p=0.003), OP3 (p=0.001) and ∑OPs (p=0.003) showed significant changes, while the amplitude of OP4 did not (p=0.05). In the non-ischaemic CRVO eye group, the average amplitudes of OP1, OP2, OP3, OP4 and ∑OPs were 10.72±1.13, 25.19±3.45, 14.72±1.94, 6.27±1.18 and 56.92±6.79 μV, respectively, which equalled 55.6%, 56.5%, 49.4%, 40.0% and 52.1% of those of the unaffected eyes, which showed significant difference between groups (p<0.001 for all). Compared with the non-ischaemic CRVO eyes, the ischaemic CRVO eyes had significantly different amplitudes of OP1 (p=0.001), OP2 (p=0.001), OP3 (p=0.042) and ∑OPs (p=0.002) and were found to be statistically different. There were no differences in the amplitudes of OP4 between groups (p=0.148) (figure 2A).

Table 3. Oscillatory potential findings of acute CRVO.

	Ischaemic CRVO (n=11)			Non-ischaemic CRVO (n=32)			Ischaemic versusnon-ischaemic CRVO eye
	CRVO eye	Unaffected eye	P value	CRVO eye	Unaffected eye	P value	P value
DA 3 OP1 am (μV)	3.41±1.07	15.04±1.57	0.000***	10.72±1.13	19.28±1.51	0.000***	0.001***
DA 3 OP1 pt (ms)	18.22±0.49	18.91±0.44	0.314	19.21±0.39	19.65±1.48	0.761	0.064
DA 3 OP2 am (μV)	8.31±3.30	39.22±5.90	0.003**	25.19±3.45	44.60±3.71	0.000***	0.001***
DA 3 OP2 pt (ms)	25.91±0.59	25.46±0.45	0.471	26.01±0.39	25.21±0.45	0.136	0.673
DA 3 OP3 am (μV)	7.80±2.16	20.66±2.97	0.001***	14.72±1.94	29.80±2.58	0.000***	0.042*
DA 3 OP3 pt (ms)	32.83±1.11	31.77±0.57	0.279	32.08±1.11	31.77±0.39	0.015*	0.855
DA 3 OP4 am (μV)	2.90±1.39	8.62±1.98	0.050*	6.27±1.18	15.67±1.56	0.000***	0.148
DA 3 OP4 pt (ms)	40.39±1.23	39.40±0.69	0.394	39.30±0.45	37.72±0.34	0.004**	0.694
∑OPs (μV)	22.38±7.01	83.53±9.93	0.003**	56.92±6.79	109.20±8.05	0.000***	0.002**

The significant differences between the groups are indicated as *p≤0.05, **p≤0.01, ***p≤0.001.

amamplitudeCRVOcentral retinal vein occlusionDAdark-adaptedLAlight-adaptedOPoscillatory potential∑OPssum of DA 3 OP1–4 amplitudesptpeak time

Figure 2. Dark-adapted 3 oscillatory potential (OP) electroretinography (ERG) parameters. The mean amplitude (A) and peak time (B) of dark-adapted 3 OP component characteristics are shown for each group. The significant differences between the groups are indicated as *p≤0.05, **p≤0.01, ***p≤0.001. CRVO, central retinal vein occlusion.

No peak time delay was found in any of the OPs, even in the ischaemic CRVO eye. There were no differences in peak time for OP1, OP2 or OP3 (p=0.314, p=0.471 and p=0.279, respectively) in the ischaemic CRVO groups, or for OP1, OP2 or OP3 (p=0.761, p=0.136 and p=0.015, respectively) in the non-ischaemic CRVO groups. Additionally, these parameters did not significantly differ between the ischaemic and non-ischaemic CRVO groups (p=0.064, p=0.673 and p=0.855, respectively) . The peak time of OP4 was 40.39±1.23 ms (39.40±0.69 ms for unaffected eye, p=0.394) in ischaemic CRVO eyes versus 39.30±0.45 ms (37.72±0.34 ms for unaffected eye, p=0.003) in non-ischaemic CRVO eyes. This difference was not significant between groups (p=0.694) (figure 2B).

Discussion

In acute CRVO, it is necessary to evaluate the ischaemic or non-ischaemic status for subsequent treatment. ERG is a non-invasive functional test and an objective measure of retinal function, and has been demonstrated to have high sensitivity and specificity for predicting ‘ischemic CRVO’. Which ERG parameter is most useful for monitoring the ischaemic CRVO is in controversy with the previous ISCEV standard; therefore, we explored this parameter again according to the new ISCEV standard 2015 and 2022 with more detailed ERG components in this study.^{10 17}

Earlier studies revealed that the best ERG parameter (in both photopic and scotopic ERGs) for differentiating ischaemic from non-ischaemic CRVO was the b-wave amplitude.^{7 18} Hayreh et al found that the b-wave amplitude was reduced to ≤60% or by >1 SD from the normal mean value, or to ≤64–69% of that in the contralateral unaffected eye, with a sensitivity of 80–90% and a specificity of 70–80% for ischaemic CRVO when single-flash photopic and scotopic ERGs were recorded.⁷ Then, the third criterion, the ratio between the CRVO eye and the contralateral unaffected eye was corrected to ≤60–70%.¹⁷ In our study, the significant changes in the amplitude were focused on the b-wave, including those of DA 0.01 ERG, DA 3 ERG, DA 10 ERG and LA 3 ERG, and the amplitude of DA 0.01 ERG b-wave was significantly changed within and between all groups. Only the b-wave amplitudes of DA 3 ERG and DA 10 ERG in the non-ischaemic CRVO group were unchanged, which means that they were not suitable for non-ischaemic CRVO assessment but were sensitive for ischaemic CRVO.

The ERG b-wave, which is induced by potassium efflux shunted from ‘on’ bipolar cells into the vitreous humour by the Müller cells in response to retinal illumine, is generated in the middle retinal layer in which the blood supply is provided mainly by the retinal circulation. The extent of the reduction in b-wave amplitude corresponds to the severity of ischaemia.² The ERG a-wave is generated by photoreceptors in the outer layer of the retina, is provided by the choroidal circulation and is rarely affected by retinal vascular disorders.⁸ The b/a amplitude ratio is a more accurate assessment of the degree of retinal ischaemia than the b-wave amplitude alone, because the individual ERG components will be modified by multiple factors, such as preretinal or vitreous haemorrhage.¹⁹

Therefore, the b/a amplitude ratio for photopic and scotopic ERGs in the ischaemic CRVO eye was considered, because the single white flash b/a amplitude ratio was found to be the best predictor, with a sensitivity of 87.5% and specificity of 78%.⁸ If the ERG shows a low b/a amplitude ratio, the prognosis is guarded; if the b/a amplitude ratio is normal or higher than normal, the prognosis is more favourable. This complication of neovascular glaucoma did not develop in any patient with a b/a amplitude ratio greater than 1.¹⁹ Brown et al found that the eyes with electroretinogram b-wave amplitude reduction to ≤60% of the corresponding a-wave amplitude were at the high risk of preproliferative (ischaemic) CRVO.¹⁸ In our study, all the b/a amplitude ratios of the ischaemic CRVO eyes were significantly lower in the ischaemic CRVO group than in the contralateral unaffected eyes, but were not changed in the non-ischaemic CRVO group. Our study confirmed again that the b-wave amplitudes (reduced ≤60%), especially for DA 0.01 ERG and LA 3 ERG, and the b/a amplitude ratios for DA 3 ERG, DA 10 ERG and LA 3 ERG are especially useful ERG-based indicators of ischaemia.

Retinal ischaemia caused by CRVO may lead to reduced photoreceptor sensitivity and a delayed peak time. There is evidence that the cone peak times, especially the cone b-wave peak times in both photopic and scotopic 30 Hz flicker ERGs, could be a suitable method of identifying ocular ischaemia and constitute reasonable criteria for the prediction of neovascularisation development.^{20 21} It was suggested that ischaemic CRVO should be defined by a peak time of ≥37 ms in the 30 Hz flicker ERG.^{22 23} Kjeka et al reported that a peak time of >35.0 ms (>0.5 SD from mean) for photopic cone b-wave in 30 Hz flicker was a good indicator of ocular neovascularisation.²⁴ Another study found that initial retinal ischaemia could be verified using the cone b-wave peak time in 30 Hz flicker ERG, with peak times of 33.7±2.4 ms in the non-ischaemic patients and 38.8±1.8 ms in patients with ischaemia.²⁰ Among the ERG component features, we found that both the peak time and the amplitude of 30 Hz flicker ERG seem to be especially good indicators of ischaemia, with criteria of peak time ≥36 ms and amplitude ≤35% of the value from unaffected eyes.

The amplitudes of the inner retinal components of ERG, such as the DA 3 OPs and PhNR amplitudes, were predominantly affected by CRVO.¹² As the most sensitive markers of ERG, OPs are reported to be a reliable quantitative method for detecting ischaemic retinal diseases in early stages, even though other ERG changes are not obvious at that time.²⁵ The averaged OP amplitudes of the maximum responses of the full-field ERGs were significantly reduced at baseline compared with those of the contralateral unaffected eyes.^{12 26} We found that the ∑OP amplitude was reduced to 26.2% in ischaemic CRVO eyes and 52.1% in non-ischaemic CRVO eyes compared with that of the unaffected eyes. The ∑OP amplitudes of ischaemic CRVO eyes were 39.3% of that of non-ischaemic CRVO eyes.

Increased attention to analytical methods for OPs and measurement could be helpful in increasing ERG sensitivity to CRVO.^{27 28} OPs are low-amplitude, high-frequency potentials seen riding on the ascending limb of the b-wave of ERG. There are usually three main positive peaks often followed by a fourth smaller peak. Early OPs have been attributed to activity in bipolar and photoreceptor cells in the outer retina, whereas later OPs are associated with the inner retinal ganglion and amacrine cells.^{12 29} Recently, the individual analysis of OP1–4 instead of the merged OPs was proposed to measuring for more thorough diagnosis and analysis of patients with retinal disease.³⁰ We found that the OP amplitude was reduced to 26.2–37.8% in ischaemic CRVO eyes and 40.0–52.1% in non-ischaemic CRVO eyes from that of unaffected eyes. The significant changes in OP amplitude were focused on OP1, OP2 and OP3 since they expressed the highest OP amplitude. The reduced OPs suggest the early involvement of amacrine cells in CRVO eyes which are thought to reflect the function of the inner and middle retina and to be sensitive to changes in retinal circulation.³¹ The amplitudes of OP1, OP2, OP3 and ∑OPs were reduced to 40% in the CRVO eyes compared with the controls, making OP measurement a reliable quantitative method for detecting ischaemic retinal diseases, even in early stage. No significant difference was found between the groups for OP4 amplitude, which was in accordance with Sefandarmaz’s report.²⁷ However, Li et al suggested the amplitude of OP4 as a good measure for early detection of retinal damage in diabetic retinopathy.³² Among OP wavelets, the final OP4 physiologically shows the smallest amplitude, allowing a longer time for detection of changes compared with the other wavelets. Significantly, the peak time of OP wave was not involved, which indicated that ischaemia had little effect on it. It has been frequently observed that the alterations primarily concern wave amplitudes, while the peak times do not seem to be affected until later, when the changes have progressed further.³¹

In conclusion, ERG investigates the response of the entire retina and is widely used for functional assessment in retinal vein occlusion. Although the diagnosis of CRVO is mostly clinical and is usually confirmed by some imaging evidence, our proposed method by using the ERG signal may help ophthalmologists to definitively diagnose ischaemic CRVO in some equivocal cases; such information on the ischaemic severity of CRVO can inform future treatment strategies.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.