Visual Performance after a Unilateral or Bilateral Implantation of Enlarged Depth-of-Focus Intraocular Lens in Patients with Cataract: A Prospective Clinical Trial

Purpose To investigate visual performances after a unilateral or bilateral implantation of enlarged depth-of-focus intraocular lens in patients with cataract. Methods In this prospective study, uneventful phacoemulsification and TECNIS® Symfony intraocular lens implantation were performed in 20 eyes of 17 patients. At postoperative 1, 4, and 12 weeks, the logarithm of the minimal angle of resolution visual acuity at far, intermediate, and near distances and the spherical equivalent in manifest refraction and automated refraction were measured. A questionnaire was used to investigate glare, spectacle dependency, and satisfaction at 12 weeks. The mean numerical error and mean absolute error were compared between intraocular lens formulas to assess the best-fit formula. Results The logarithm of the minimal angle of resolution visual acuity significantly improved to 0.02 at far, 0.02 at intermediate, and 0.27 at near distances at 12 weeks (p < 0.05). Spherical equivalent was −0.79 D on automated refraction and was significantly lower than −0.26 D measured on manifest refraction. Patients' satisfaction score was 9.06, 8.94, and 6.65 for far, intermediate, and near distances, respectively. Near glasses were required in 5 patients and 2 patients complained of photic phenomenon. Visual performances were not significantly different between bilateral and unilateral implanted patients. No patients reported bilateral imbalance due to unilateral surgery. The mean numerical error was closest to 0 D using the Barrett Universal II formula. The mean absolute error was not significantly different between these formulas. Conclusion Unilateral or bilateral implantation of the enlarged depth-of-focus intraocular lens seems to be equally effective in improving visual performances in patients with cataract.


Introduction
With the advancement of the intraocular lens (IOL), cataract surgery has become an operation not only to replace an opaque crystalline lens with a clear intraocular lens but also a procedure to correct the refractive error and presbyopia [1,2]. Initially, bifocal IOLs were available, but as the demand for intermediate vision inpatients using computers increased, trifocal IOLs became popular [3,4]. However, bifocal or trifocal IOLs have limitation that the working distances between these fixed focal points are involved in suboptimal visual acuity [5][6][7]. A newly developed enlarged depth-of-focus (EDOF) IOL may provide better optical quality on the whole addition range than fixed multifocal IOLs with a proprietary achromatic diffractive surface designed to correct chromatic aberration and a echelette feature to extend the range of vision [5,8].
Recently, a few reports comparing TECNIS ® Symfony IOL with other multifocal IOLs have been published and reported good intermediate visual outcomes compared to other IOLs [9,10]. However, most previous studies included only patients who underwent bilateral surgery and did not analyse the refractive changes [11,12]. In addition, few reports investigated the subjective satisfaction with unilateral bifocal IOL implantation but not with EDOF lens [13,14]. is study aimed to report visual performances including refractive outcomes, subjective satisfaction, and spectacle independence in patients undergoing unilateral or bilateral TECNIS ® Symfony IOL implantation.

Patients.
is prospective study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of Seoul National University Hospital (IRB no. 1612-133-820). e study was conducted from February 2017 to May 2018. Twenty eyes of 17 patients who visited ophthalmology outpatient clinic of Seoul National University Hospital for the cataract surgery and were willing to participate in the study were included. All included participants signed a consent form.

Clinical Evaluation.
e primary outcomes of the study were improvement of visual acuity at near, intermediate, and far. Secondary outcomes included presence of photic phenomena and spectacle independence for daily tasks.
Corrected distance visual acuities (CDVA) were measured before the surgery, and 1, 4, and 12 weeks after the surgery to evaluate the safety index. Uncorrected visual acuities (UCVA) were measured at far (5 m), intermediate (66 cm), and near (40 cm) distances preoperatively, and then 1, 4, and 12 weeks postoperatively. Snellen visual acuities were converted to the logarithm of minimal angle of resolution (LogMAR) for statistical analysis. orough ophthalmic examinations including intraocular pressure, slitlamp examination, and keratometry were conducted at every follow-up.
Automated refraction (AR) and manifest refraction (MR) were performed at postoperative 1, 4, and 12 weeks. e IOL master 700 (Carl Zeiss Meditec AG, Jena, Germany) was used to calculate SRK/T, Holladay 2, Haigis, and Hoffer Q formulas. e Barrett Universal II and Hill-RBF formulas were calculated by inputting the values measured by IOL master 700 measurements into the online software. e refraction prediction error was calculated as the difference between the actual postoperative manifest refraction and the predicted refraction for each formula. e mean numerical error (MNE) was defined as the arithmetic mean of the prediction errors, and the mean absolute error (MAE) was defined as the mean of the magnitude of the prediction errors.
To evaluate the patients' subjective outcome, a questionnaire was used as previously described [11]. Patient's satisfaction score in near, intermediate, and far tasks was measured from 0 (unsatisfactory) to 10 (very satisfactory) at postoperative 4 and 12 weeks. Patients were asked regarding their spectacle dependencies at near, far, and intermediate distances with 0%, 25%, 50%, 75%, and 100% of time. Photic phenomena were evaluated using an open question whether the patients had any problems with their vision such as glare or halos.
In order to increase compliance of the patients, each outpatient visit was informed in advance. All data were recorded in electronic medical charts, and all data were collected by two independent ophthalmologists.

Statistical Analysis.
All statistical analyses were conducted using Prism software (GraphPad Prism version 7, Inc. La Jolla, CA, USA). To compare quantitative variable between the data at two time points or between unilateral and bilateral implantation, a nonparametric Mann-Whitney U test was used, and to compare the changes over time within a group, the paired t-test was used. To compare two time points, Wilcoxon matched-pairs signed-rank test was used, and to compare three or more time points, repeated measures analysis of variance (rANOVA) was used. Data were presented as the mean ± standard deviation (SD), and the differences were considered significant at p < 0.05.

Results
A total of 20 eyes of 17 patients were enrolled, and all patients completed a 12-week follow-up. Among them, 3 patients (n � 6 eyes) underwent bilateral EDOF lens implantation and the other 14 patients underwent unilateral EDOF lens implantation. e demographic and preoperative data of patients are summarised in Table 1. Of the 14 patients who underwent unilateral surgery, the opposite eye was excluded because it did not meet the inclusion criteria. Two eyes were pseudophakic, 8 eyes were without significant cataract, 2 eyes had epiretinal membrane, 1 eye had severe astigmatism, and 1 eye had history of previous refractive surgery. e spherical equivalent (SE) of the opposite eyes was −0.26 ± 2.22 D.
e Barrett Universal II formula also had the lowest MAE of 0.25 ± 0.25 D but was not significantly different from other formulas (Figure 3(e)).

Contrast Sensitivity Test and Glare Test.
Contrast sensitivity values at all spatial frequencies were within normal limits at 4 and 12 weeks postoperatively. Contrast sensitivity increased to12 cycles per degree at postoperative 12 weeks compared with that of the postoperative 4 weeks (p � 0.0273, paired t-test) (Figure 4(a)). Mean scores of the glare test was 15796.9 ± 8459.5 at postoperative 4 weeks and 15418.4 ± 7788.3 at postoperative 12 weeks. e difference between the two time points was not statistically significant (p � 0.7197, Wilcoxon matched-pairs signed-rank test) (Figure 4(b)).

Patient Satisfaction, Spectacle Dependence, and Photic
Phenomena. Patients' satisfaction score was 9.06 ± 2.08 for far, 8.94 ± 1.30 for intermediate, and 6.65 ± 2.67 for neardistance vision at postoperative 12 weeks. Patients' satisfaction scores were significantly higher at far (p � 0.0327, rANOVA) and intermediate (p � 0.0031, rANOVA) distance vision than at near vision. No significant difference in patients' satisfaction score was observed between bilateral and unilateral surgery groups at all distances (Figure 2(b)).
All patients did not need a spectacle at far and intermediate distances at 12 weeks postoperatively. In near tasks, two of the unilateral surgery patients required wearing spectacles for <50% of the time, and two unilateral surgery patients and one bilateral surgery patient required spectacles for >50% of the time. No clinically significant difference in spectacle dependency was observed between unilateral and bilateral surgery groups (>0.9999, Fisher's exact test) (Figure 2(c)).
Only two patients complained of glare at postoperative 12 weeks. Only one patient reported bilateral imbalance due to unilateral surgery (7.2%).

Discussion
In the eyes implanted with TECNIS ® Symfony IOL, the UCVA at far, intermediate, and near distances was significantly improved just a day after the surgery and well maintained for 3 months. As with the previous results, [18,19] which ranged from 0.08 to 0.00, excellent mean logMAR UDVA of 0.02 ± 0.11 was also obtained at 12 weeks in our study. is confirms the ability of the EDOF IOL to gain near vision without sacrificing distance vision. e mean logMAR uncorrected intermediate visual acuity (UIVA) of 0.02 and uncorrected near visual acuity (UNVA) of 0.27 were also within the normal range of visual acuities as previously reported [19,20]. Along with previous studies in which the logMAR UNVA ranged from 0.30 to 0.20, [21] the monocular UNVA in our study, when compared with monocular UNVA in other multifocal IOLs measured at 40 cm, was inferior to that of +3.0 D bifocal IOL, AcrySof ® IQ ReSTOR ® (Alcon Laboratories, Inc., Fort Worth, TX, USA), ranging from 0.15 to 0.05, [3,10] but compatible with UNVA of 0.23 with AT Lisa ® tri 839MP (Carl Zeiss Meditec AG, Jena, Germany) or 0.24 with Fine Vision IOL (Physiol, Liege, Belgium) [22,23]. e TECNIS ® Symfony IOL is considered to be better suited for patients who spend more time on intermediate-distance tasks, such as computer work, rather than near-distance tasks, such as reading or using mobile phones. In patients with a demand for near-field work that is closer than 40 cm, a micromonovision technique can be adopted as reported by Cochener et al. [11].

Journal of Ophthalmology
Regarding the refractive outcome, patients achieved SE within ± 0.5 D in 18 eyes (90%) and within ± 1.0 D in all eyes. To the authors' best knowledge, no report has been conducted on the distribution of SE; therefore, our results could not be compared with previous studies. Instead, the mean SE value of all previous reports was within ± 0.5 D [10,11,19]. is excellent refraction predictability is believed to have contributed to good distance visual acuity. One of the important findings revealed in this study is that the SE measured by AR was significantly more myopic than the SE measured by MR, with a mean difference of −0.53 D. Munoz et al. reported that AR showed poor correlation for spherical values with a trend toward more negative values in refractive multifocal IOL [24]. Bissen-Miyajima et al. reported a good correlation between AR and MR in a full aperture diffractive TECNIS ® bifocal IOL with pupil independency [25]. However, TECNIS ® Symfony IOL in a pupil-dependent posterior diffractive design has a dominant peak at the intermediate point, and a pupil of <2 mm produces continuous peak from far to intermediate focus, which may result in a difference between AR and MR [26,27].
To achieve optimal performance of multifocal IOL, accurate IOL power calculation is essential. To the authors' knowledge, no previous report has investigated a formula that fit best in TECNIS ® Symfony IOL, and Cochener et al.  [28]. SRK/T, Holladay 2, Haigis, Hoffer Q, Barrett Universal II, and Hill-RBF formulas used in this study also showed high accuracy of 65 to 85% within ± 0.5 D and 95 to 100% within ±1.0 D. Based on our results, the Barrett Universal II formula showed an MNE that is closest to 0 D and the tendency towards lowest MAE; therefore, the Barrett Universal II formula could be considered as a first reference.
Most previous studies using multifocal IOL have been performed bilaterally, and reports on unilateral surgery are limited [7,12]. According to previous reports, unilateral multifocal IOL implantation could achieve high spectacle independence and stereoacuity, but significantly less than that after the bilateral surgery [29,30]. Unlike the previous studies, the patient satisfaction score was as high as 9.06 for far, 8.94 for intermediate, and 6.65 for near vision, even though the ratio of unilateral surgery patients was 82.4%, showing no significant difference in patient satisfaction score or spectacle dependence between binocular and monocular surgery patients. In addition, 92.8% of patients did not complain of binocular disparity in patients who underwent the unilateral surgery. erefore, EDOF IOL can be effectively used in patients who have presbyopia and unilateral cataract and require good intermediate vision for computer or navigator use.

Conclusions
In conclusion, TECNIS ® Symfony IOL restores excellent visual acuity especially at far and intermediate distances.
High accuracy can be achieved by using third-and fourthgeneration IOL formulas and evaluating postoperative refractions by MR. e satisfaction levels were high in both unilateral and bilateral patients with low spectacle dependence and no binocular disparity in unilateral surgery patients. erefore, TECNIS ® Symfony IOL can be effectively used in not only bilateral cataract patients but also in unilateral patients with presbyopia.

Data Availability
e data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest
e authors declare that there are no conflicts of interest.