Evaluation of Fundus Function in Mature Cataract Patients by Visual Electrophysiology

Purpose To explore the value of visual electrophysiology in evaluating the fundus function of mature cataract patients. Methods 124 mature cataract patients (153 eyes) were examined before cataract surgery; the examinations included best corrected visual acuity (BCVA), pattern visual evoked potential (PVEP), full-field electroretinogram (ffERG), and multifocal electroretinogram (mfERG). According to the postoperative fundus conditions, the subjects were divided into two groups: the no fundus disease group and the fundus disease group. Approximately one month after the operation, BCVA was measured, and visual electrophysiology was performed on subjects who had a stable fundus condition and had not received treatment for fundus disease. Results One month after cataract surgery, BCVA ≤ 0.3 logMAR was found in 60 eyes (96.8%) without fundus disease and 59 eyes (64.8%) with fundus disease. Compared with the group without fundus disease, the preoperative electrophysiological examination of the group with fundus disease showed that the amplitude of ffERG waves and the amplitude density of the P1 wave in the 2nd to 5th rings of mfERG were decreased (all P < 0.05). ffERG and mfERG can be used for differential diagnosis of fundus disease (all P < 0.05), while PVEP has no significant diagnostic value for fundus disease (all P > 0.05). In the group without fundus disease, the amplitude of the PVEP 15′ P100 wave and the amplitude of dark-adapted (DA) 0.01 b-wave, DA 3.0 a-wave, and DA 10.0 a-wave were negatively correlated with postoperative logMAR BCVA (all P < 0.05). In the group with fundus disease, the amplitude of PVEP and ffERG and the amplitude density of mfERG were negatively correlated with postoperative logMAR BCVA (all P < 0.05). In the eyes of cortical cataracts, some parameters of PVEP, ffERG, and mfERG were significantly different before and after surgery. In the eyes of nuclear cataracts, some parameters of ffERG and mfERG were significantly different before and after surgery. In the eyes of posterior subcapsular cataracts, some parameters of PVEP and ffERG were significantly different before and after surgery. Conclusions ffERG and mfERG can be used to detect fundus disease in mature cataract patients. The preoperative visual electrophysiological examination has high clinical value in predicting postoperative vision of mature cataract patients with fundus disease. Different types of cataracts have different effects on electrophysiological examination results. When interpreting the electrophysiological report, it is necessary to consider the existence of cataracts. This trial is registered with 2019-K068.


Introduction
Cataract surgery is one of the most frequently performed surgeries in the world.Many patients ask doctors about the recovery of vision after cataract surgery and before cataract surgery and have high expectations for cataract surgery.In fact, if the patient has other problems with the fundus, the improvement of vision after surgery is not particularly ideal.Unfortunately, many patients wait until the lens is completely turbid before coming to the hospital for treatment.Because of the opacity of the lens, many ophthalmic examinations to check the structure and function of the fundus cannot be carried out, and the assessment of the condition of the fundus is more difcult.Failure to identify fundus disease before cataract surgery may make patients have unrealistically high expectations or even make patients think that surgery has caused fundus problems [1].Terefore, it is an important part of preoperative communication between doctors and patients to evaluate fundus function and explain the prognosis before cataract surgery.
At present, the common examination methods for ocular fundus disease include direct/indirect ophthalmoscopy, ocular B-ultrasound, and optical coherence tomography (OCT).Ophthalmoscope and OCT are easily afected by refractive medium turbidity [2].Although ocular Bultrasound is not afected by refractive medium turbidity, its accuracy in diagnosing retinopathy is not high [1,3].In recent years, objective visual electrophysiology technology has been widely studied by cataract experts [4,5].
Te visual electrophysiological examination includes a series of noninvasive tests to provide objective indicators of functions related to diferent positions and cell types of the visual system [6].Although the related research of visual electrophysiology as a preoperative examination of cataract has been reported, the feasibility evaluation of its application in mature cataract patients is diferent [7,8].Moreover, few studies have associated pattern visual evoked potential (PVEP), full-feld electroretinogram (fERG), and multifocal electroretinogram (mfERG) with fundus conditions and postoperative vision.Te purpose of this study is to study the evaluation value of visual electrophysiology on the fundus function of mature cataract patients and provide an objective basis for preoperative doctor-patient communication.

Materials and Methods
2.1.Subjects.Tis study was performed in line with the principles of the Declaration of Helsinki.Approval was granted by the Ethics Committee of the Afliated Hospital of Nantong University.Informed consent was obtained from all participating subjects after they were given an explanation of the study.
Te inclusion criteria included cataract patients with a Lens Opacities Classifcation System III grade of ≥3 for nuclear, cortical, or posterior subcapsular cataracts, and their fundus structure could not be observed.Te exclusion criteria included patients whose pupils cannot be fully dispersed (<7 mm); patients with a history of vitreous surgery; patients whose fundus could not be seen clearly after cataract surgery; patients with serious complications during and after the operation; and patients who could not cooperate in completing various examinations.
All subjects underwent routine eye examination before an operation, including visual acuity test, optometry, intraocular pressure assessment, Pentacam three-dimensional anterior segment analysis, inspection of the optical biometric instruments, ultrasonic biomicroscopy, ophthalmology ultrasound A scan, ophthalmology ultrasound B scans, fundus photography, and OCT.According to the International Society for Clinical Electrophysiology of Vision (ISCEV) standard, the visual electrophysiological apparatus (RETI-Port/Scan 21, Roland) was used to carry out the visual electrophysiological examination for each subject, including pattern visual evoked potential (PVEP), full-feld electroretinogram (fERG), and multifocal electroretinogram (mfERG).
After cataract surgery, all subjects underwent fundus examination after mydriasis, including indirect fundus endoscopy, fundus photography, ophthalmology ultrasound B scans, and OCT.According to the postoperative fundus conditions, the subjects were divided into two groups: the no fundus disease group and the fundus disease group.Approximately one month after the operation, the subjects with stable fundus condition and without treatment for fundus disease were subject to visual electrophysiological examination, and the best corrected visual acuity (BCVA) was recorded.

PVEP.
Te PVEP test was performed in accordance with the ISCEV standards in 2016.[9] A black-and-white checkerboard pattern was reversed to stimulate at a frequency of 2 reversals per second (rps).Two check element sizes were used: 1 °and 15′.Te feld size was 17 °, the mean luminance was 50 cd/m 2 , and the contrast of the black-andwhite checkerboards was 97%.Te pupil of the tested eye was in a natural state, and the subjects with ametropia wore glasses for correction.Te active electrode (gold cup electrode) was placed 2 cm above the occipital trochanter, the reference electrode (gold cup electrode) was placed on the forehead, and the ground electrode (gold cup electrode) was placed on the mastoid process.Under normal lighting, the subject sat 1 m away from the display screen for examination, recorded with one eye, and wore a light-tight eye mask on the opposite eye.In order to ensure repeatability, PVEP was scanned 64 times each time and recorded twice.

fERG.
Te fERG test was conducted following the ISCEV standards in 2015 [10].Te pupils were dilated to the maximum, at least 7 mm, with 0.5% tropicamide, and the cornea was anaesthetized with 0.5% proparacaine hydrochloride (ALCAINE).Te active electrode (gold foil electrode) was placed at the inferior conjunctival fornix, the reference electrode (gold cup electrode) was placed near each orbital rim, and the ground electrode (gold cup electrode) was placed at the forehead.Stimulations were generated by a Ganzfeld Q450 stimulator.After dark adaptation for more than 20 min, dark-adapted (DA) 0.01 ERG, DA 3.0 ERG, DA 3.0 oscillatory potentials (OPs), and DA 10.0 ERG were detected in the dark room in sequence.Ten, lightadapted (LA) 3.0 ERG and LA 30 Hz ERG were performed after 10 min of light adaptation.

mfERG.
Te mfERG test was performed in accordance with the 2021 ISCEV standards [11].Te pupils were dilated to the maximum, at least 7 mm, with 0.5% tropicamide, and the cornea was anaesthetized with 0.5% proparacaine hydrochloride (ALCAINE).Te subjects with ametropia wore glasses for correction.Te placement of the electrode was the same as that used for fERG.Te resolution was 61 hexagonal stimulation units.Te viewing distance from the subject to the monitor was fxed at 30 cm.Te view angle was 27 °.Under normal lighting, monocular recording was performed, and the opposite eye was equipped with an opaque eye mask.

Statistical Analysis.
Statistical analysis was performed using IBM SPSS Statistics for Windows (version 26.0,IBM Corp).Data are presented as the mean ± standard deviation.Visual acuity data were converted to the logarithm of the minimal angle of resolution to calculate the mean.Te results of electrophysiological examination before operation in the group without fundus disease and the group with fundus disease were compared by independent sample t-test.Te area under the receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specifcity of visual electrophysiological examination to distinguish whether there was fundus disease or not.Te optimal diagnostic cutof point was obtained by using the maximum value of the Youden index (YI � sensitivity + specifcity − 1).Pearson's correlation analysis was used to explore the correlation between the preoperative electrophysiological parameters and the postsurgical logMAR BCVA values.Te results of electrophysiological examination before and after operation were compared by paired sample t-test.Signifcance was accepted at the P < 0.05 level.

Clinical Details of Subjects.
A total of 124 cataract patients (153 eyes) aged 42-84 years with an average age of 64.91 ± 9.35 years were recruited.Among them, 61 eyes were age-related cataracts, 57 eyes were diabetes cataracts, 34 eyes were complicated cataracts, and 1 eye was traumatic cataract.Visual acuity prior to cataract surgery ranged between logMAR 4.0 and 0.3.Te postsurgical classifcation of the cataract patients based on the fundus condition within one month after cataract surgery resulted in 62 eyes in the group without fundus disease (aged 48-84 years; average 65.77 ± 8.72) and 91 eyes in the group with fundus disease (aged 42-81 years; average 64.32 ± 9.75).Tere was no signifcant diference in age between the two groups (t � 0.945, P � 0.346).Fundus diseases included 37 eyes of diabetes retinopathy, 30 eyes of high myopia, 8 eyes of retinitis pigmentosa, 5 eyes of macular degeneration, 5 eyes of epiretinal membrane, 3 eyes of old uveitis, 1 eye of central retinal vein occlusion, 1 eye of lamellar hole in the macular region, and 1 eye of amblyopia.Intravitreous drug injection was performed in 12 eyes during cataract surgery, and retinal laser treatment was performed in 4 eyes after cataract surgery.BCVA measurement and visual electrophysiological examination were performed in 29 eyes (46.77%) and 47 eyes (51.65%) of the group without and with fundus disease, respectively, one month after the operation.Te vision of all cataract patients improved after surgery.Te BCVA of the two groups of patients before and after surgery is shown in Table 1.One month after the operation, BCVA ≤ 0.3 log-MAR was found in 60 eyes (96.8%) without fundus disease and 59 eyes (64.8%) with fundus disease.

Comparison of Preoperative Visual Electrophysiology
between Groups without and with Fundus Disease.Te electrophysiological examination results of the group without fundus disease and the group with fundus disease before cataract surgery were compared by independent sample t-test (Table 2).In the group with fundus disease, the peak time of the PVEP 1 °P100 wave was delayed, the amplitude of the fERG wave was decreased, and the amplitude density of the P1 wave in the 2nd to 5th rings of mfERG was decreased (all P < 0.05).However, the peak time and amplitude of the PVEP 1 °and 15′ P100 waves, and the amplitude density of the P1 wave in the frst ring of mfERG were not signifcantly diferent between the two groups (all P > 0.05).

ROC Curves as Diagnostic Indicators for Detecting Fundus
Disease.In all cataract patients, the ROC curves of using visual electrophysiology to detect whether there is fundus disease are shown in Figures 1-3.Te optimal cut-of value, sensitivity, specifcity, and the area under the ROC curve (AUC) of each electrophysiological parameter are shown in Table 3. Te amplitudes of each fERG wave and the amplitude density of P1 waves in the 1st to 5th rings of mfERG can be used to distinguish whether there is fundus disease (all AUC ≥ 0.612, P < 0.05), while the peak time and amplitude of PVEP cannot distinguish whether there is fundus disease (all AUC ≥ 0.503, P ≥ 0.05).

Correlation between Preoperative Electrophysiological Examination and Postoperative BCVA in the Two Groups.
In the group without fundus disease, the amplitudes of the PVEP 15′ P100 wave, fERG DA 0.01 b-wave, DA 3.0 a-wave, and DA 10.0 a-wave were negatively correlated with postoperative logMAR BCVA (all P < 0.05) (Figures 4 and 5).Te peak time and amplitude of the PVEP 1 °P100 wave, the peak time of the PVEP 15′ P100 wave, the amplitude of the fERG DA 3.0 b-wave, DA 10.0 b-wave, DA OP2 wave, LA 3.0 a-wave, LA 3.0 b-wave, and LA 30 Hz P2 wave, and the amplitude density of the P1 wave in the 1st to 5th rings of mfERG have no signifcant correlation with logMAR BCVA after the operation (all P > 0.05) (Figures 4-6).
In the group with fundus disease, the amplitudes of PVEP and fERG were negatively correlated with postoperative logMAR BCVA (all P > 0.05) (Figures 4 and 5).Te amplitude density of the P1 wave in the 1st to 5th rings of mfERG before the operation was negatively correlated with postoperative logMAR BCVA (all P > 0.05) (Figure 6).Tere was no signifcant correlation between the peak time of the PVEP 1 °and 15′ P100 waves and postoperative logMAR BCVA (all P > 0.05) (Figure 4).In the eyes of cortical cataracts, after cataract surgery, the amplitude of the PVEP 1 °and 15′ P100 waves, the amplitude of the fERG LA 3.0 b-wave, and the amplitude density of the  P1 wave in the 1st, 2nd, and 5th rings of mfERG were higher than before surgery (Table 4).
In the eyes of nuclear cataracts, after cataract surgery, the amplitudes of the fERG DA 3.0 a-wave, DA 10.0 a-wave, LA 3.0 b-wave, and LA 30 Hz P2 wave, as well as the amplitude density of the P1 wave in the frst ring of mfERG, were higher than before surgery (Table 5).
In the eyes of the posterior subcapsular cataract, after cataract surgery, the peak time of the PVEP 15′ P100 wave was delayed, the amplitude of the fERG DA 0.01 b-wave decreased, and the amplitude of the fERG LA 3.0 b-wave increased compared to preoperative subcapsular cataract (Table 6).

Discussion
As early as 1951, researchers used visual electrophysiological techniques to predict the postoperative vision of cataract patients [12].Subsequent research shows that preoperative visual electrophysiological examination plays an important  clinical value in the management of cataract with fundus diseases such as diabetes retinopathy, age-related macular degeneration, high myopia, and uveitis [4,[13][14][15].In clinical practice, the fundus diseases of cataract patients are complex and diverse.To accurately identify the location of fundus disease, multiple examination methods may be needed.In this study, the combined application of three visual electrophysiological techniques includes the quantitative positioning function of the optic nerve, macular, and each layer of the retina.PVEP is currently the most important method to detect whether there is conduction dysfunction in optic nerve diseases, and it has the advantages of high sensitivity, stability, and repeatability [6,16].Terefore, to detect optic nerve disease before cataract surgery, PVEP was selected for this study.fERG is the overall response of the retina to a transient fash, which can generally distinguish the dysfunction of the inner or outer retina and the dysfunction of the rod or cone cell system [10,17].However, fERG is mainly produced by the retina rather than the macula, and the role of the macula is very limited.Te electrophysiological assessment of macular function requires the use of diferent techniques, such as pattern ERG or multifocal ERG [6].mfERG technology is a method to record the local electrophysiological response of the posterior pole retina, which is often used to detect macular diseases.Additionally, mfERG can locate lesions and has a unique diagnostic value for some unexplained diseases that lead to reduced vision but no obvious changes in the fundus, such as cone cell dystrophy, acute regional occult outer retinopathy, occult macular dystrophy, and chloroquine toxic retinopathy [11,18].Terefore, to distinguish between macular disease and retinopathy as a whole, we chose mfGER as a supplement to fERG.Fundus disease will not only afect the recovery of vision after cataract surgery but also afect the selection of intraocular lenses before surgery and the selection of a surgical plan.For cataract patients with retinal diseases or vision pathway diseases, the results of visual electrophysiology are usually abnormal.Mori et al. [8] found that patients with abnormal TFC results before cataract surgery were usually found to have complications related to retinal or optic nerve damage after surgery.Wang et al. [4] examined the value of standardized electrophysiological techniques in evaluating the retinal function of diabetes cataract patients and found that the DA 10.0 ERG a-wave dominated by rods may give the most sensitive indication of potential difuse retinal

6
Journal of Ophthalmology dysfunction and retinopathy.In this study, the amplitude of each wave of fERG and the amplitude density of the 2-5th ring of mfERG in cataract patients with fundus disease were signifcantly lower than those in cataract patients without fundus disease.Both fERG and mfERG have diferential diagnostic values in the diagnosis of fundus disease.Among them, the amplitude density of the fourth ring of mfERG has the highest diagnostic value, with AUC of 0.826, sensitivity of 0.790, specifcity of 0.736, and YI of 0.526.In this study, 12 eyes were treated with intravitreal drug injection during cataract surgery, including 10 eyes with diabetes retinopathy, 1 eye with central retinal vein occlusion, and 1 eye with high myopia retinopathy with choroidal neovascularization.Te fundus of these 12 eyes could not be seen clearly before an operation, but the OPs of fERG showed a signifcant abnormality, suggesting the need for treatment.Tis shows that visual electrophysiological examination has important clinical guiding signifcance for the selection of cataract surgery methods.
In our study, almost all cataract patients without fundus disease had a good recovery of vision after surgery, while 35.2% of cataract patients with fundus disease had logMAR BCVA more than 0.3 after surgery.Clinically, we can judge that some cataract patients have fundus lesions according to their medical history, but due to the occlusion of cataracts, we cannot judge the severity of fundus lesions and predict the recovery of visual function after surgery.An et al. [19] performed preoperative electrophysiological examination on 150 cataract patients without obvious other eye diseases and found that the center point amplitude of mfERG, the peak time, and amplitude of fERG DA 3.0 b-wave were related to postoperative vision, while the peak time and amplitude of PVEP and the amplitude density of mfERG were not signifcantly correlated with postoperative vision.In this study, we found that the postoperative vision of cataract patients without fundus disease was only correlated with the amplitude of the PVEP 15′ P100 wave, fERG DA 0.01 b-wave, DA 3.0 a-wave, and DA 10.0 a-wave but not  Journal of Ophthalmology with other indicators.However, we were surprised to fnd that the amplitude of PVEP, the amplitude of fERG, and the amplitude density of mfERG were signifcantly correlated with postoperative vision when we analyzed the correlation between preoperative electrophysiology and postoperative vision in the group with fundus disease.Previously, Ji et al. [14] found that the amplitude and peak time of preoperative ERG were signifcantly correlated with postoperative BCVA when discussing the visual outcome and prognostic factors of patients with Vogt-Koyanagi-Harada syndrome after cataract surgery.Terefore, we believe that preoperative visual electrophysiological examination has high clinical value in predicting the postoperative vision of cataract patients with fundus disease.Some researchers believe that mature cataracts itself will not signifcantly change the results of  [7,20].Some researchers believe that turbid crystals can reduce the clarity of stimulus pattern contour or contrast of stimulus through defocusing and light-absorption effects, thereby reducing visual electrophysiological parameters [21,22].de Waard et al. [23] reported that the diferent types of cataracts display diferent light scatter characteristics.Tam et al. [24] reported that the amplitude density of mfERGs was afected diferently in the diferent areas of the retina because of the light scattering by a cataract.In order to investigate the impact of diferent types of cataracts on electrophysiological examination results, we analyzed the changes in visual electrophysiology before and after surgery for diferent types of cataracts.Our research results indicate that cortical cataract can afect the results of PVEP, fERG, and mfERG, with nuclear cataract having minimal impact on PVEP and posterior subcapsular cataract having minimal impact on mfERG.In future clinical work, we need to consider the presence of cataracts when interpreting electrophysiological results reports.In order to better apply electrophysiological examination to cataract patients, we can choose more suitable electrophysiological examination items based on the type of cataract.
In conclusion, the international standard visual electrophysiological examination can be used to detect whether mature cataract patients have fundus disease before surgery and have high clinical value in predicting the postoperative vision of mature cataract patients with fundus disease.Diferent types of cataracts have diferent efects on electrophysiological examination results.When interpreting electrophysiological results, we need to consider the presence of cataracts.

Figure 5 :
Figure 5: Plots showing the correlation between fERG parameters and postoperative logMAR BCVA.

Table 1 :
BCVA before and after cataract surgery in two groups.
nations based on the main opacity site of the lens.We analyzed the electrophysiological changes before and after surgery in 26 eyes with cortical cataracts, 27 eyes with nuclear cataracts, and 23 eyes with posterior subcapsular cataracts.

Table 2 :
Comparison of preoperative visual electrophysiology between groups without and with fundus disease.

Table 3 :
Optimal cut-of point, sensitivity, specifcity, and AUC of each electrophysiological parameter.

Table 4 :
Changes in visual electrophysiology before and after cortical cataract surgery.