Tear Film Stability Affects Visual Acuity After Implantations of Monofocal and Multifocal Intraocular Lenses: An Evaluation by Objective Scatter Index

Abstract

Purpose: To assess the impact of tear film on postoperative visual acuity after cataract surgery to implant an intraocular lens (IOL).

Methods: Tear break-up time (TBUT), Schirmer I test, objective scatter index (OSI), and uncorrected distance visual acuity (UCDVA), intermediate visual acuity (UCIVA), and near visual acuity (UCNVA) were collected 6 months after cataract surgery.

Results: Fifteen eyes with monofocal (Mo-) IOLs and 15 eyes with multifocal (Mu-) IOLs from 30 subjects were included. The Mu-IOL group exhibited higher baseline OSI (1.92 ± 0.69, P < 0.001). Negative correlations—both groups: tear film–related OSI (TF-OSI) and TBUT/Schirmer I test; Mo-IOL: TBUT and logMAR UCDVA—and positive correlations—both groups: TF-OSI and baseline OSI, baseline OSI/TF-OSI and logMAR UCDVA; Mu-IOL: baseline OSI/TF-OSI and logMAR UCIVA/UCNVA—were found. Linear regression showed associations between TF-OSI and TBUT (Mo-IOL: R² = 0.455, P = 0.006; Mu-IOL: R² = 0.454, P = 0.006)/Schirmer I test (Mo-IOL: R² = 0.527, P = 0.002; Mu-IOL: R² = 0.266, P = 0.049). Multiple regression showed associations between baseline OSI (Mo-IOL: R² = 0.309, P = 0.032; Mu-IOL: R² = 0.305, P = 0.033)/TF-OSI (Mo-IOL: R² = 0.332, P = 0.025; Mu-IOL: R² = 0.523, P = 0.002)/TBUT (Mo-IOL only: R² = 0.315, P = 0.029) and logMAR UCDVA.

Conclusions: TF-OSI reflects the UCDVA performance in eyes with IOLs and facilitates a better understanding of the effects of the tear film.

Translational Relevance: TF-OSI offers a developmental and objective approach to assessing the changing visual performance caused by tear film after cataract surgery and IOL implantation in clinical practices.

Introduction

Age-related cataract is a common disease in the elderly population. In modern days, cataract surgery has been profoundly enhanced. With the introduction and advancement of intraocular lens (IOL) technology, postsurgical refractive errors can be effectively corrected.¹ Monofocal (Mo-) IOL offers sufficient distance vision, but presbyopic spectacles are needed for intermediate and near demands.² With advances in optical design, refractive cataract surgery with multifocal (Mu-) IOL implantation provides patients who are pursuing spectacle independence with other options. The technology of diffractive rings enables the Mu-IOLs to separate light into different foci, thus forging images both distant and near.³ 

Nonetheless, patients may experience a decline in visual quality and ocular discomfort due to tear film dysfunction, and the results of surgery may fall short of their expectations.⁴ Dry eye resulting from abnormal tear quantity or quality occurs in more than one in 10 patients undergoing cataract surgery.⁵ The abnormity is a multifactorial result of ocular surface inflammation, goblet cell loss, incisional corneal nerve damage, eye drop preservatives, meibomian gland dysfunction, and intraoperative trauma.^4,6 Consequently, the jeopardized integrity of the tear film results in optical disturbances, including aberrations and light scattering in dry eyes. In contrast with the expectations of patients who have had IOLs implanted, tear film instability leads to complaints of blur, glare, and decreased visual acuity.^7,8 The dissatisfying visual acuity caused by unstable tear film may easily be ignored by ophthalmologists in their clinical practices. It is difficult to objectively evaluate the reduction in visual acuity caused by malfunctioning tear film with routine inspection,⁹ and questionnaires can reflect an unexpected bias.¹⁰ The dynamic objective scatter index (OSI) collected over a span of 20 seconds provides a reliable means to detect interference with optical quality due to tear film instability.¹¹ The variations in optical quality are objectively recorded by calculating serial light beams reflected from the retina in a double-pass system,¹² which assists ophthalmologists in evaluating visual performance after cataract surgery. 

The objective of the current study was to assess the effectiveness of OSI in evaluating the impact of tear film stability on visual acuity. Moreover, differences in visual acuity influenced by tear film in eyes implanted with Mo-IOLs and Mu-IOLs were investigated to provide possible references for clinical application. 

Materials and Methods

Subjects

A total of 30 subjects underwent cataract surgery at the Department of Ophthalmology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University; they were randomly recruited for this case–control study. The study involved 15 eyes with Mo-IOLs and 15 eyes with Mu-IOLs from these 30 subjects 6 months after cataract surgery. All surgeries were performed by an experienced surgeon. Topical anesthesia and standard phacoemulsification with IOL implantation were performed. There were no surgical complications. 

This study was approved by the institutional review board of Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University (ethical number: 2023027-01). All study protocols adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained from all participants. 

All of the subjects met the following inclusion criteria: axial length range of 22.0 to 25.0 mm, corneal astigmatism less than 1.0 diopter (D), corneal endothelial cell density greater than 2000/mm², and no pupillary abnormality. The exclusion criteria were as follows: history of dry eye preoperatively (the subjects included in this study had no dry eye symptoms such as dryness, foreign body sensation, burning sensation, fatigue, discomfort, redness, itching, or visual fluctuations); preoperative tear break-up time (TBUT) ≥ 10 seconds; negative fluorescein sodium corneal and conjunctival staining; surgery other than cataract surgery; ocular trauma; corneal pathology; glaucoma; uveitis; retinopathy; optic neuropathy; high myopia; systemic diseases; or rupture of the posterior capsule during the cataract surgery. 

Assessment

Six months after the cataract surgery, the subjects underwent comprehensive inspections that included uncorrected distance visual acuity (UCDVA), TBUT measurement, Schirmer I test, and OSI examination. For those who received Mu-IOL implantation, uncorrected intermediate visual acuity (UCIVA) and uncorrected near visual acuity (UCNVA) were evaluated. An experienced ophthalmologist obtained TBUT measurements and Schirmer I tests for all of the subjects. 

Visual acuity was assessed by using logarithm of the minimum angle of resolution (logMAR) acuity charts to convert visual acuity into logMAR values. The logMAR Early Treatment of Diabetic Retinopathy Study (ETDRS) tumbling-E charts of distance vision (5 m), intermediate vision (60 cm), and near vision (33 cm) were presented in front of the examined subjects at the corresponding distances. The eye not being tested was covered by an opaque occluder during the visual acuity assessment. The score was recorded as the logMAR level of the last attempted line with the total value of the missed letters on that line and the previous line, with each letter equaling 0.02. The monocular UCDVA was recorded at 5 m, the monocular UCIVA was recorded at 60 cm, and the monocular UCNVA was recorded at 33 cm. Tear film stability was measured using TBUT. A single fluorescein strip was moistened with a drop of preservative-free normal saline and placed over the inferior tear meniscus to measure TBUT. The seconds were counted from the first blink until the tear film surface ruptured, halting another blink. The average times of three tests were recorded. Tear production was examined after TBUT measurement by using the Schirmer I test without topical anesthesia. A standard paper strip was inserted into one-third of the mid-lateral area of the lower fornix and the length of the wetting column was measured in millimeters after 5 minutes. An optical quality analysis system (OQAS II; Visiometrics, Terrassa, Spain) was used to evaluate the baseline OSI and mean value of the 20-second dynamic OSI. The dynamic OSI was recorded with the OQAS by measuring the objective scattering index value every 0.5 second for 20 seconds, which varied with changes in the tear film. The average plotting curve depicting the scattering index changes over time is shown in Supplementary Data S1. The tear film–related OSI (TF-OSI) was calculated by subtracting the baseline OSI from the mean value of the dynamic real-time OSI obtained from each inspection. The same experienced ophthalmic technician conducted all of the aforementioned examinations on the same day for each subject. 

Intraocular Lenses

PCB00 (Mo-IOL)

The TECNIS Monofocal ZMB00 IOL (Abbott Medical Optics, Santa Ana, CA) is a modified, preloaded, C-loop Mo-IOL that is made from hydrophobic acrylic polymers and has an aspheric optical design. The overall length of the IOL is 13 mm, and it has an optic diameter of 6 mm.¹³ 

ZMB00 (Mu-IOL)

The TECNIS Multifocal ZMB00 IOL (Abbott Medical Optics) is composed of hydrophobic acrylic material and is designed as a single piece with a C-loop and square edges. With a near addition of 4.0 D (3.0 D on the spectacle plane), the back of the IOL features 22 concentric diffractive rings. The IOL has an overall length of 13 mm and an optic diameter of 6 mm.¹⁴ 

Statistical Analysis

We compared the sociodemographic and clinical variables of the two groups using a two-sample t-test for continuous variables and Pearson's χ² test for categorical variables. Results are presented as means ± standard deviations (SDs). To examine the relationships between continuous variables of interest in the two groups separately, we conducted Pearson's correlation (r) tests. Spearman's correlation tests (r_s) were conducted for categorical variables. We then conducted linear regression models with the baseline OSI or TF-OSI as the dependent variable to investigate the association of the TBUT or Schirmer I test result with the objective OSI parameters. Later, we explored multivariable linear regression models with UCDVA, UCIVA, and UCNVA as the dependent variable in order to investigate the association of the baseline OSI, TF-OSI, TBUT, or Schirmer I test with visual acuity. Age, gender, laterality of the eye, and ocular axial length (AL) were included as covariates. We used Cook's distance to detect potential influential points that may have affected our models, but we did not find any. The sample size was evaluated by using PASS 15 software, and the power for each multiple regression was above 0.85. We conducted the statistical analysis using SPSS Statistics 26 (IBM, Chicago, IL). 

Results

Characteristics of the Subjects

The present study included a cohort of 30 subjects (Table 1). The mean age was 68.60 years. Nineteen of the 30 participants were female. Sixteen of the 30 eyes investigated were right eyes. The mean AL was 23.64 mm. The baseline OSI of the Mu-IOL group (1.92 ± 0.69) was significantly higher than that of the Mo-IOL group (1.00 ± 0.43) (***P < 0.001). The two groups did not differ in age, gender, laterality of eye, AL, TBUT, Schirmer I test, TF-OSI, or logMAR UCDVA (P > 0.05). The logMAR UCIVA and UCNVA were not examined for the Mo-IOL group. Additionally, there were no significant differences between the two groups in terms of pupil size, spherical diopter, cylindrical diopter, spherical equivalent, preoperative TBUT, or TBUT variation (the difference between preoperative and postoperative TBUT) as shown in Supplementary Data S2, S3, and S4. 

Table 1.

 

Characteristics of the Subjects 6 Months After Cataract Surgery

 

Correlations Among Variables

The relationships among the variables were investigated. Pearson's correlation tests were performed on the continuous variables, including age, AL, TBUT, Schirmer I test, baseline OSI, TF-OSI, UCDVA, UCIVA, and UCNVA. The correlations among gender, ocular laterality, and the other variables were analyzed by Spearman's correlation tests. 

Among all of the variables of the Mo-IOL group (Table 2), TBUT was negatively correlated with TF-OSI (r = –0.674, **P = 0.006) and logMAR UCDVA (r = –0.562, *P = 0.029); Schirmer I test was found to be negatively correlated with TF-OSI (r = –0.726, **P = 0.002); basline OSI was found to be positively correlated with TF-OSI (r = 0.533, *P = 0.041) and logMAR UCDVA (r = 0.556, *P = 0.032); and TF-OSI was also found to be positively correlated with logMAR UCDVA (r = 0.576, *P = 0.025). 

Table 2.

 

Correlation of Parameters in the Subjects Who Received Mo-IOL Implantation

 

Similar relationships were observed in the Mu-IOL group (Table 3). A negative correlation was found between TBUT and TF-OSI (r = –0.673, **P = 0.006). Another negative correlation was found between the Schirmer I test and TF-OSI (r = –0.516, *P = 0.049). Positive correlations were found between baseline OSI and TF-OSI (r = 0.730, **P = 0.002), baseline OSI and logMAR UCDVA (r = 0.552, *P = 0.033), TF-OSI and logMAR UCDVA (r = 0.723, **P = 0.002), and logMAR UCIVA and logMAR UCNVA (r = 0.596, *P = 0.019). 

Table 3.

 

Correlation of Parameters in the Subjects Who Received Mu-IOL Implantation

 

TF-OSI is Associated With Objective Dry Eye Indicators

To further evaluate the capability of OSI in predicting dry eye, we assessed the associations between the objective dry eye indicators (TBUT as well as Schirmer I test) and the OSI parameters (baseline OSI as well as TF-OSI). Linear regression was performed between the variables (Table 4, Fig.). TF-OSI was found to be negatively associated with TBUT in the Mo-IOL group (R² = 0.455, β = –2.906, **P = 0.006) and the Mu-IOL group (R² = 0.454, β = –3.881, **P = 0.006). Similarly, negative associations were also found between TF-OSI and the Schirmer I test in the Mo-IOL group (R² = 0.527, β = –3.225, **P = 0.002) and the Mu-IOL group (R² = 0.266, β = –2.778, *P = 0.049). However, there was no significant association between baseline OSI and the objective dry eye indicators in the two groups. 

Table 4.

 

Exploratory Model of OSI Associated With TBUT and Schirmer I Test by Linear Regression

 

Figure.

 

Exploratory models of linear regression were used to examine the association between TF-OSI and TBUT (A), as well as the association between TF-OSI and the Schirmer I test (B), in both the Mo-IOL and Mu-IOL groups. After adjusting for age, gender, laterality of eye, and AL, exploratory models of multiple linear regression were utilized to investigate the association between baseline OSI and logMAR UCDVA (C), the association between TF-OSI and logMAR UCDVA (D), and the association between TBUT and logMAR UCDVA (D), in both the Mo-IOL and Mu-IOL groups. Significant models were established for baseline OSI/TF-OSI and logMAR UCDVA in both groups. However, only the model for TBUT and logMAR UCDVA in the Mo-IOL group was found to be significant (E). *P < 0.05, **P < 0.01, ***P < 0.001, n. s. = not significant.

Associations Among Different Factors and Visual Acuity

Forward multiple linear regression models was performed to explore the identifying factors associated with logMAR UCDVA in the Mo-IOL group or logMAR UCDVA, UCIVA, or UCNVA in the Mu-IOL group (Table 5). No significant model was found when the TBUT, Schirmer I test, baseline OSI, and OSI were simultaneously entered for regression exploration. Stepwise, we investigated models that associate visual acuity with TBUT, Schirmer I test, baseline OSI, or OSI alone, with adjustment of age, gender, laterality of eye, and AL. Several models were established (Fig.). Baseline OSI was positively associated with logMAR UCDVA in both the Mo-IOL group (R² = 0.309, β = 0.065, *P = 0.032) and the Mu-IOL group (R² = 0.305, β = 0.067, *P = 0.033). TF-OSI was also positively associated with logMAR UCDVA in both the Mo-IOL group (R² = 0.332, β = 0.056, *P = 0.025) and the Mu-IOL group (R² = 0.523, β = 0.108, **P = 0.002). Finally, TBUT was found to be negatively associated with logMAR UCDVA in the Mo-IOL group (R² = 0.315, β = –0.013, *P = 0.029). No other significant association was found among the variables. 

Table 5.

 

Exploratory Model of Factors Associated With UCDVA, UCIVA and UCNVA by Stepwise Multiple Regression

 

Discussion

The visual differences related to Mo-IOL and Mu-IOL have long been hotly debated in cataract research. However, there has been little research on how tear film stability affects the varying visual acuity of different types of IOLs. In the formation of optical imaging of the eyes, tear film corrects the intercellular irregularities of corneal epithelium as a component of the refractive system.¹⁵ Universally, cataract surgery poses a risk to the production and stability of tear film due to inflammation and trauma of the ocular surface, which can lead to dysfunction of the meibomian glands, loss of goblet cells, and damage to the corneal, as well as conjunctival epithelium.^6,16 Furthermore, elderly individuals are more susceptible to light scattering within the visual system due to dry environments then young individuals, suggesting that patients with age-related cataract who receive IOL implants are easily affected by tear film instability.¹⁷ Despite the successful implementation of cataract surgery and IOL implantation, unstable tear film leads to blurred vision, visual fluctuations, and reduced contrast sensitivity.^18,19 Therefore, there is a need for accurate evaluation of indicators to provide better evaluation of visual acuity correlated with tear film function after cataract surgery and IOL implantation. 

In the present study, we compared the capability of the TBUT and Schirmer I test and the baseline OSI and TF-OSI in evaluating the tear film–related changes in visual quality for eyes implanted with either Mo-IOLs or Mu-IOLs. Although tear film stability and tear secretion could be detected by TBUT and the Schirmer I test,²⁰ simultaneous real-time OSI also allows the ophthalmologists to dynamically assess the tear film optical quality in a controllable environment.²¹ Previous research has shown that the OSI, in combination with pupil retro-illumination and contrast sensitivity, is helpful in evaluating tear film dynamics.²² The OSI serves as an objective approach to evaluating the stability and permeability of the ocular refractive system. This is achieved by measuring the eccentric intensity of light-beam scattering during double-pass imaging at the visual axis.¹¹ After excluding the baseline index, the TF-OSI represents the mean value of tear film–related dynamic OSI variations.²³ Nevertheless, questionnaires were not used in the current study due to concerns about potential bias resulting from cultural and emotional differences among the cataract patients.^10,24 Other objective index values, including noninvasive tear film break-up time (NITBUT), conjunctival redness score (CRS), and tear meniscus height (TMH), were reported to monitor stability of the tear film. Previous studies found that the quality of vision was significant improved by treatment with intense pulsed light in patients with evaporative dry eye or meibomian gland dysfunction, along with improvement of the NITBUT, CRS, and other subjective parameters.^25,26 Another study reported no enhanced visual acuity and TMH in the dry eye patients who received elastic silicon punctal plugs.²⁷ These objective parameters can be collected by a computerized system based on slit-lamp microscopy. We believe that these objective index values offer their own advantages in reflecting tear film condition. The NITBUT captures the time point of damage to the surface integrity of the tear film with an automated camera. Different from the TBUT as measured by ophthalmologists, the NITBUT is more accurate in timing; however, it is a technical extension of measuring the TBUT and is not able to represent the average status of a tear film in a time frame as dynamically as OSI. The CRS, nevertheless, is easily affected by ocular surface inflammation, and the TMH can be influenced by the conjunctival sac volume. Therefore, we consider that TF-OSI is an advancement in evaluating tear film stability over a period of time. 

No significant differences were found between the two groups in terms of age, gender, laterality of eye, AL, TBUT, Schirmer I test, TF-OSI, or logMAR UCDVA (Table 1), thus indicating a consistency in the basic backgrounds of the included subjects. UCDVA was studied based on the realistic expectation of providing good spectacle-independent distance visual acuity²⁸ due to advancements made in IOL technology. The comparable results of logMAR UCDVA between the two groups are consistent with the reports of several former studies.^29–31 

UCIVA and UCNVA were not investigated in the Mo-IOL study, as the use of presbyopic spectacles may cause background differences when compared with the Mu-IOL. As is shown (Table 1), the baseline OSI of the Mo-IOL group showed significantly better performance than that of the Mu-IOL group. An earlier study reported a similarly higher baseline OSI in the patients who received Mu-IOL implants than those with Mo-IOLs.³² The difference may be attributed to the distinct optical structures of the two types of IOLs. As light-distortion indices could be enhanced by the diffractive rings characterizing Mu-IOL structure,³³ the baseline OSI is hence increased. 

Several variables involved in the current study were interrelated. Significant correlations were found among the TBUT, Schirmer I test, baseline OSI, logMAR UCDVA, and TF-OSI, as well as between baseline OSI and logMAR UCDVA, in both the Mo-IOL and Mu-IOL groups (Tables 2, 3). Given its capacity to serve as a dry eye indicator and to evaluate the overall ocular scattering state and distance vision, TF-OSI is a sensitive indicator. 

The TF-OSI measures the scattering power of the ocular refractive system over a period. Therefore, the only factor that can cause refractive power changes in the ocular surface during this short period is variation in the tear film. As reported in a previous study,³⁴ apparently higher TF-OSI was found in the dry eye patients, and it was also positively correlated with the lipid layer thickness of tear film. Respectively, the sensitivity and specificity of TF-OSI were 0.811 and 0.810, with an area under the curve of 0.900. Moreover, linear regression models incorporating TF-OSI and independent dry eye indicators were successfully implemented in the current study (Table 4, Fig.), revealing the potential of TF-OSI to predict tear film stability. 

An earlier study reported a positive correlation between the baseline OSI before intranasal neurostimulation and TF-OSI.³⁵ TF-OSI provides a continuous record of the ocular scattering power that reflects the tear film–related component of the total OSI. This accounts for the significant correlation between TF-OSI and baseline OSI (Tables 2, 3). Additionally, a greater ocular scattering power usually leads to decreased visual acuity due to extensive optical degradation,^36,37 which is why there was a correlation between TF-OSI and baseline OSI, and logMAR UCDVA. The multiple linear regression model was used to predict the visual acuities of different distances based on baseline OSI, TF-OSI, TBUT, or Schirmer I test values (Table 5). After adjusting for age, gender, laterality of eye, and AL, significant models were only established for the dependent variable of logMAR UCDVA with baseline OSI and TF-OSI in both the Mo-IOL and Mu-IOL groups (Fig.). Subsequently, better UCDVA was predicted for lower baseline OSI and TF-OSI. Unexpectedly, the logMAR UCDVA demonstrated a correlation with the baseline OSI in the Mo-IOL group but not in the Mu-IOL group. We propose that the position of the tear film breaking point may be the underlying cause. During clinical examinations of TBUT, we observed that the tear film membrane ruptured spontaneously at random sites on the corneal surface. When a subject with the Mu-IOL looks into the distance, accommodation relaxes and the pupil dilates, exposing the outer diffractive rings.³ The light refracted by the inner diffractive rings focuses in front of the retina, leaving the rupturing tear film in the inner pupillary area without being noticed. In contrast, tear film ruptures in the pupil area interfere with the light refracted by the Mo-IOL with its single refractive surface. This result reveals the limitation of the TBUT examination. However, further experiments are still necessary to confirm this hypothesis. In the cases of UCIVA and UCNVA, no significant models were developed for the Mu-IOL group. This possibly resulted from the fact that the OSI is recorded through retinal imaging in an optical double-pass system with corrected distance vision.³⁸ 

The capability of baseline OSI and TF-OSI to predict UCDVA for the Mu-IOL and Mo-IOL groups attracted our attention. The regression models based on the baseline OSI accounted for 30.9% and 30.5% of the variations in logMAR UCDVA observed in the Mo-IOL and Mu-IOL groups, respectively (Table 5). The similarity of the β and t values between the two groups resulted in similar effects of baseline OSI on UCDVA in the eyes with Mo-IOLs and Mu-IOLs. The model of TF-OSI showed different patterns. The model accounted for 33.2% of the logMAR UCDVA with the TF-OSI in the Mo-IOL group, but 52.3% in the Mu-IOL group (Table 5). The β and t values were also higher in the Mu-IOL group. These results demonstrate that the ability of TF-OSI to predict UCDVA is greater in eyes implanted with Mu-IOLs. This may also be attributed to the characteristics of diffractive rings. The changing refraction of the tear film may have a great impact on the Mu-IOL due to the optical rings.^3,39 This result is distinct from the association between the TBUT and Schirmer I test and UCDVA (Table 5). A possible explanation is that TF-OSI reveals the comprehensive stability of a tear film in a simultaneous dynamic period, making it a robust approach. Despite their accessibility, traditional examinations that include the TBUT and Schirmer I test may lead to unsatisfactory reliability.⁴⁰ 

Conclusions

The impact of tear film stability on visual acuity following cataract surgery with IOL implantation was investigated in this study as a developmental application of OSI. Whereas the baseline OSI measures the overall extent of light scattering in the refractive system of the eye, associations between the TF-OSI and dry eye indicators reflect the variations in tear film over a specific period of time. The TF-OSI showed greater sensitivity in predicting the UCDVA of eyes with IOLs. Compared with the traditional indicators of dry eye, the mild effects of tear film instability on UCDVA can also be sensitively reflected by TF-OSI, especially in eyes with Mu-IOLs. The tear film state represented by TF-OSI had a more significant impact on the UCDVA of eyes with Mu-IOLs than on eyes with Mo-IOLs. TF-OSI could be an effective parameter for evaluating the distance visual acuity of eyes with IOL implants in future clinical practices. 

Acknowledgments

Supported by the Initial Scientific Research Fund of Doctors in Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University. 

Disclosure: H. Huang, None; J. Yan, None; B. Li, None; M. Huang, None; S. Guo, None; A. Fan, None; W. Liu, None