Bilateral Implantation of a Single-Piece Bifocal Diffractive Intraocular Lens in Presbyopic Patients: A Prospective Case Series. John S.M.

ORIGINAL CLINICAL STUDY Bilateral Implantation of a Single-Piece Bifocal Diffractive Intraocular Lens in Presbyopic Patients: A Prospective Case Series John S.M. Chang, MD Purpose: To report visual outcomes and quality after bilateral implantation of a single-piece diffractive multifocal intraocular lens (MIOL) with a bifocal design. Design: Prospective, observational case series. Methods: All presbyopic subjects were implanted with the ZMB00 MIOL (Abbott Medical Optics) at the Hong Kong Sanatorium and Hospital. We evaluated the distance, intermediate, and near visual acuity (VA) under photopic and mesopic conditions; contrast sensitivity with and without glare under photopic and mesopic conditions; quality of vision; and rate of spectacle independence. Results: A total of 36 subjects were included. No intraoperative complications developed. At the 6-month visit, the mean (± standard deviation) monocular uncorrected VAs at distance, intermediate, and near were 0.01 ± 0.12, 0.26 ± 0.17, and 0.09 ± 0.08, respectively. The respective mean binocular uncorrected VAs were 0.05 ± 0.09, 0.12 ± 0.13, and 0.04 ± 0.06. No eyes lost any corrected distance VA. The binocular contrast sensitivity was significantly better without glare than with glare under photopic and mesopic conditions (P < 0.05 for all spatial frequencies under both conditions). A total of 21 (58%) and 21 subjects (58%) reported halo and glare, respectively. Thirty subjects (83%) reported complete spectacle independence. Conclusions: Bilateral implantation of the bifocal MIOL in presbyopic patients with or without cataract was safe in satisfactory vision and a high rate of spectacle independence. Halos and glare were common. especially contribute 2 distinct foci for clear distance and near vision while retaining some intermediate vision. The Tecnis ZMB00 (Abbott Medical Optics, Inc, Santa Ana, CA, US) is a bifocal diffractive MIOL that has been studied in presbyopic patients with and without cataract. 3,5 11 These studies have shown that this MIOL has provided satisfactory vision at distance, intermediate, and near and contrast sensitivity (CS) under photopic and mesopic conditions. Most patients who received this MIOL have also reported high rates of spectacle independence and satisfaction. However, no previous study of this MIOL has simultaneously presented data on CS with and without glare under different light conditions. Kamiya et al 12 reviewed 50 cases of MIOL explantation and identified decreased CS and the presence of glare and other photic phenomena as the most common reasons for the explantation. Therefore, it is important to investigate the effects of glare on the CS of the ZMB00 under different light conditions. The current study evaluated these aspects of visual performance and the ease with which patients performed daily tasks after bilateral implantation of the ZMB00. We also compared the results between patients who underwent presbyopic lens exchange and cataract surgery to assess the difference in level of satisfaction and between the 3- and 6-month postoperative time points to assess the speed of recovery. Key Words: bifocal, cataract, multifocal, presbyopia, phacoemulsification (Asia Pac J Ophthalmol (Phila) 2019;8:12 21) Multifocal intraocular lenses (MIOLs) have been widely used to restore vision at various distances after cataract surgery and refractive lens exchange. 1 4 With a bifocal design, MIOLs From the Department of Ophthalmology, Hong Kong Sanatorium and Hospital, Hong Kong. Submitted April 16, 2018; accepted August 1, 2018. The study was sponsored by a grant by Abbott Medical Optics, Inc for the cost of assessments. The author declares that there is no conflict of interest regarding the publication of this paper. The author received travel expenses from Abbott Medical Optics, Inc.; Alcon Laboratories Inc.; and Technolas Perfect Vision and lecture honorarium from Alcon Laboratories Inc. Reprints: John S.M. Chang, Hong Kong Sanatorium and Hospital, 8/F, Li Shu Pui Block, Phase II, 2 Village Road, Happy Valley, Hong Kong. E-mail: johnchang@hksh.com. Copyright 2019 by Asia Pacific Academy of Ophthalmology ISSN: 2162-0989 DOI: 10.22608/APO.2018152 METHODS Patients This prospective case series included patients who underwent cataract surgery or refractive lens exchange with bilateral implantation of the ZMB00 MIOL between August 2012 and April 2014 at the Hong Kong Sanatorium and Hospital. The inclusion criteria were patients aged 40 years or older with preoperative corneal astigmatism of 1.75 diopters (D) or less. The exclusion criteria were preexisting ocular conditions including age-related macular degeneration and glaucoma, systemic diseases such as uncontrolled diabetes mellitus that might affect the postoperative vision, Fuchs dystrophy, and a history of corneal refractive surgery. The author (J.S.M.C.) performed all surgeries. Patient consent has been obtained. The current study was conducted in accordance with the Declaration of Helsinki and with approval obtained from the hospital ethics committee. Preoperative Examination A comprehensive eye examination was performed preoperatively, which included a detailed history taking with special attention to the presence of dry eye disease, visual 12 www.apjo.org

Bifocal Diffractive IOL in Presbyopic Patients distortion, and systemic diseases such as thyroid dysfunction, uncontrolled diabetes mellitus, and rheumatoid symptoms; noncycloplegic subjective refraction, manual keratometry; and automated keratometry by IOLMaster (Version 5.4; Carl Zeiss Meditec AG, Jena, Germany). Optical coherence tomography was obtained from the macula in case of suspicion of diseases and the patient was not implanted with MIOLs if any abnormality was found. The axial length and anterior chamber depth were measured using the IOLMaster. The Haigis 13 and SRK/T formulas 14 were used for intraocular lens (IOL) power calculations. Intraocular Lens The ZMB00 is a single-piece, foldable, ultraviolet-blocking, acrylic diffractive MIOL with +4 D near addition (about +3.2 D at the spectacle plane). The MIOL has a biconvex design with an anterior aspheric surface and a posterior diffractive surface. The overall diameter is 13 mm and the optic diameter is 6 mm. The energy distribution between the distance and near foci is symmetrical (50/50) and independent of pupil size. 5,6,11 Surgical Technique All surgeries were performed under topical anesthesia (oxybuprocaine 0.4%) and intracameral lidocaine 1% or 2%. Preoperatively, the surgeon used nepafenac ophthalmic suspension 0.1% (Nevanac; Alcon Laboratories Inc, Fort Worth, TX, US), and 0.5% tropicamide 0.5% phenylephrine hydrochloride 0.5% (Mydrin-P, Santen Pharmaceutical Co, Ltd, Osaka, Japan). A 2.25-mm clear corneal incision was created either superiorly or temporally with a keratome. DisCoVisc ophthalmic viscosurgical device (Alcon Laboratories Inc) was injected into the anterior chamber and a manual continuous curvilinear capsulorrhexis was created with a forceps. After hydrodissection and nuclear splitting, coaxial phacoemulsification was performed using the Infiniti Vision System (Alcon Laboratories Inc). Irrigation/ aspiration of the residual cortex and posterior capsule polishing were performed using a coaxial system. All IOLs were placed in the capsular bag. Limbal relaxing incision was indicated when the incision location was not at the steep axis of a corneal astigmatism that exceeded 0.75 D. Postoperative Examination Subjects were evaluated at 1 day, 1 week, and 1, 3, and 6 months postoperatively. Additional follow-up visits were scheduled as needed. To ensure consistent findings, the same optometrist performed all refraction and other visual assessments. The results at the 3- and 6-month visits were reported. The study outcomes under photopic condition were the noncycloplegic subjective refraction; keratometry; monocular and binocular uncorrected distance visual acuity (UDVA) at 3 m, corrected distance VA (CDVA) at 3 m, uncorrected intermediate VA (UIVA) at 67 cm, distance-corrected intermediate VA (DCIVA) at 67 cm, uncorrected near VA (UNVA) at 33 cm, and distancecorrected near VA (DCNVA) at 33 cm; and binocular distancecorrected CS with and without glare at the spatial frequencies of 3, 6, 12, and 18 cycles per degree (cpd). The study outcomes under mesopic condition were the binocular CDVA, DCIVA at 67 cm, and DCNVA at 33 cm under mesopic condition; binocular distance-corrected CS with and without glare at the spatial frequencies of 3, 6, 12, and 18 cpd; and pupil size. The intermediate and near VAs were measured using the SLOAN Two-Side ETDRS Format Near Vision Chart (Precision Vision, La Salle, IL, US) (designed for use at 40 cm). The actual VA at its corresponding distance was calculated by the visual angle subtended and then converted to the logarithm of the minimum angle of resolution (logmar) for statistical analyses. The CS was recorded using the CSV-1000E chart (Vector Vision). The mesopic pupillary size was measured using the Colvard Pupillometer (Oasis Medical Inc, San Dimas, CA, US). Photopic and mesopic assessments were performed at 85 and 3 candelas/m 2, respectively. Glare was simulated using the standardized Halogen Glare Test (CSV-1000HGT, Vector Vision). The same optometrist administered a questionnaire on visual quality and ease of performance of daily tasks at the 3- and 6-month visits after the second eye surgery. Statistical Analysis The statistical analyses included descriptive data of the subject demographics and visual and refractive outcomes. The Kolmogorov-Smirnov test was performed to determine the normality of the data. The paired t test (or Wilcoxon signed-rank test when the assumption of data normality was violated) was performed to compare the mesopic pupillary size, monocular and binocular VAs at different distances and under different conditions, and CS at different spatial frequencies under different conditions between the 3- and 6-month visits. The paired t test (or Wilcoxon signed-rank test) was also performed to show binocular summations, defined as the difference between the binocular and better-eye distance-corrected VA. 15 The McNemar-Bowker test was performed to compare the questionnaire results between the 3- and 6-month visits. The Mann-Whitney U test and χ 2 test (or Fisher exact test) were performed for comparison between subjects who underwent bilateral presbyopic lens exchange [defined as having a preoperative CDVA of 0.00 logmar (20/20) or above in both eyes] bilaterally and cataract surgery in 1 or both eyes [defined as having a preoperative CDVA of worse than 0.00 logmar (20/20) and cataract in 1 or both eyes]. All statistical analyses were performed using the SPSS version 16.0 (SPSS Inc, Chicago, IL, US). RESULTS Table 1 shows the demographics, preoperative ocular parameters, and surgical parameters of the 72 study eyes (36 subjects). The preoperative refraction and CDVA were unavailable for 2 eyes (3%). The mesopic pupil sizes did not differ significantly between the 3-month (mean ± SD, 4.65 ± 0.74 mm; range, 3.0 6.0 mm) and 6-month visits (mean, 4.68 ± 0.80 mm; range, 3.0 6.0 mm) (P = 0.483). Limbal relaxing incision was placed intraoperatively in 6 eyes (8%) at the time of surgery. Table 2 shows the postoperative refractive results at the 3- and 6-month visits. Figure 1 shows the cumulative percentages of the refractive outcomes. Visual Acuity Figure 1 shows the efficacy of the surgery. Table 3 shows the mean CDVA and UDVA under photopic condition at the 3- and 6-month visits. The monocular UDVA, UIVA, UNVA, CDVA, DCIVA, and DCNVA under photopic condition did not differ significantly between the 3- and 6-month visits (P > 0.05 www.apjo.org 13

Chang TABLE 1. Demographics, Preoperative Ocular Parameters, and Surgical Parameters (72 Eyes of 36 Subjects) Mean ± SD Range No. (%) of women 32 (89) Age, y 55.9 ± 6.8 44 to 72 Axial length, mm 24.70 ± 2.03 21.29 to 29.00 Anterior chamber depth, mm 3.18 ± 0.32 2.34 to 3.82 Keratometry, D 43.87 ± 1.42 41.19 to 46.63 Corneal astigmatism, D 0.55 ± 0.36 0.00 to 1.75 Sphere, D* 3.03 ± 4.99 14.00 to 5.75 Cylinder, D* 0.53 ± 0.51 0.00 to 1.75 MRSE, D* 2.76 ± 4.93 13.88 to 5.88 CDVA, logmar* 0.05 ± 0.15 0.12 to 0.88 Intraocular lens power, D 18.13 ± 6.20 5.0 to 30.0 Predicted refraction by SRK/T formula, D 0.29 ± 0.15 0.72 to 0.01 Predicted refraction by Haigis formula, D 0.00 ± 0.33 0.67 to 0.78 CDVA indicates corrected distance visual acuity; MRSE, manifest refraction spherical equivalent. *Data on preoperative refraction and corrected distance visual acuity were unavailable for 2 eyes (3%). TABLE 2. Postoperative Refraction at the 3- and 6-Month Visits (72 Eyes) Mean ± SD, D Range, D 3 Months 6 Months Within 0.50 D of emmetropia, No. (%) Within 1.00 D of emmetropia, No. (%) Mean ± SD, D Range, D Within 0.50 D of emmetropia, No. (%) Within 1.00 D of emmetropia, No. (%) Sphere 0.30 ± 0.41 1.25 to 0.75 53 (74) 71 (99) 0.26 ± 0.41 1.25 to 0.50 58 (81) 71 (99) Cylinder 0.47 ± 0.42 0.00 to 1.50 47 (65) 67 (93) 0.47 ± 0.40 0.00 to 1.50 48 (67) 68 (94) Manifest refraction spherical equivalent 0.06 ± 0.37 0.88 to 1.00 62 (86) 72 (100) 0.02 ± 0.37 0.75 to 0.88 66 (92) 72 (100) for all comparisons). Table 4 shows the mean uncorrected and distance-corrected VAs under photopic and mesopic conditions at the 3- and 6-month visits. The binocular UDVA, UIVA, and UNVA under photopic conditions and binocular CDVA, DCIVA, and DCNVA under photopic and mesopic conditions did not differ significantly between the 2 time points (P > 0.05 for all comparisons). The binocular UIVA, UNVA, DCIVA, and DCNVA were significantly worse under mesopic than photopic condition at 3- and 6-month visit (P < 0.001 for all comparisons). At the 6-month visit, the binocular distance-corrected distance, intermediate, and near VAs were significantly better than the distance-corrected VA of the better eye at corresponding distances under photopic condition (P = 0.046, <0.001, and 0.011, respectively). Figure 2 shows the cumulative percentages of monocular and binocular VA at different distances. Contrast Sensitivity Figure 3 shows the binocular CS at spatial frequencies of 3, 6, 12, and 18 cpd under photopic and mesopic conditions with and without glare at the 6-month visit. At the 3-month visit, the binocular photopic CS was significantly better than the mesopic CS at spatial frequencies of 3, 6, and 18 cpd without glare (P < 0.001, 0.021, and 0.034, respectively) and at 18 cpd with glare (P = 0.030). At the 6-month visit, the binocular photopic CS was significantly better than mesopic CS at the spatial frequencies of 3, 6, and 12 cpd without glare (P = 0.004, 0.002, and 0.025, respectively) and at 12 cpd with glare (P < 0.030). The binocular photopic CS without glare was significantly better than with glare at the 3- and 6-month visits (P 0.001 for all comparisons). The binocular mesopic CS without glare was significantly better than with glare at the 3- and 6-month visits (P 0.001 for all comparisons). The binocular CS did not differ significantly between the 3- and 6-month visits under photopic and mesopic conditions with and without glare (P > 0.05 for all comparisons). Safety and Complications No eyes lost any CDVA [after excluding 2 eyes with a postoperative CDVA of 0.10 logmar (20/15) but without the preoperative CDVA] (Fig. 1). No intraoperative complications developed and no IOL exchange was required. Questionnaire All subjects completed the questionnaire on visual quality and ease of performing daily tasks at the 3- and 6-month visits (Table 5). At the 6-month visit, 33 subjects (92%) were satisfied/ very satisfied with the uncorrected vision. Thirty subjects (83%) achieved complete spectacle independence. A total of 35 (97%), 14 www.apjo.org

Bifocal Diffractive IOL in Presbyopic Patients A B C D Overcorrected y = 0.6288x 0.0234 Undercorrected Mean: +0.00 ± 0.33 D Range: +0.78 to 0.67 D E F % changed >0.50 D Preop 6 mo = 61% Spherical Equivalent Refraction (D) 3 2 1 0 1 2 3 4 5 6 7 8 0.06 0.02 2.76 Preop (70) 3 (72) 6 (72) Time After Surgery (Months) FIGURE 1. Refractive outcomes, efficacy, and safety of 72 eyes at the 6-month visit. A, Uncorrected distance VA. B, Change in corrected distance VA. C, Spherical equivalent attempted vs achieved. D, Spherical equivalent refractive accuracy. E, Refractive astigmatism. F, Stability of spherical equivalent refraction; error bars indicate SD. CDVA indicates corrected-distance visual acuity; D, diopter; Postop, postoperative; Preop, preoperative; SER, spherical equivalent refraction; UDVA, uncorrected distance visual acuity; VA, visual acuity. Haigis-L formula was used in the illustration of SER achieved. www.apjo.org 15

Chang TABLE 3. Monocular Visual Acuity in logmar at the 3- and 6-Month Visits (72 Eyes) 3 Months 6 Months Mean ± SD Range Mean ± SD Range P value (3- vs 6-Month Visits)* Distance Photopic UDVA 0.01 ± 0.11 0.12 to 0.30 0.01 ± 0.12 0.12 to 0.40 0.578 Photopic CDVA 0.09 ± 0.06 0.12 to 0.00 0.10 ± 0.05 0.12 to 0.00 0.317 Intermediate Photopic UIVA 0.24 ± 0.14 0.03 to 0.57 0.26 ± 0.17 0.13 to 0.67 0.316 Photopic DCIVA 0.30 ± 0.12 0.03 to 0.57 0.31 ± 0.15 0.03 to 0.67 0.640 Near Photopic UNVA 0.08 ± 0.07 0.06 to 0.26 0.09 ± 0.08 0.12 to 0.32 0.250 Photopic DCNVA 0.06 ± 0.05 0.06 to 0.18 0.06 ± 0.07 0.06 to 0.22 0.293 CDVA indicates corrected distance visual acuity; DCIVA, distance-corrected intermediate visual acuity; DCNVA, distance-corrected near visual acuity; UDVA, uncorrected distance visual acuity; UIVA, uncorrected intermediate visual acuity; UNVA, uncorrected near visual acuity. *Comparison of the mean values between the 3- and 6-month visits. TABLE 4. Binocular Visual Acuity in logmar at the 3- and 6-Month Visits (36 Subjects) 3 Months 6 Months Mean ± SD Range Mean ± SD Range P value* P value P value Distance Photopic UDVA 0.06 ± 0.08 0.12 to 0.18 0.05 ± 0.09 0.12 to 0.18 0.886 1.000 0.317 Photopic CDVA 0.11 ± 0.04 0.12 to 0.00 0.11 ± 0.04 0.12 to 0.00 0.157 Mesopic CDVA 0.11 ± 0.04 0.12 to 0.00 0.11 ± 0.04 0.12 to 0.00 0.564 Intermediate Photopic UIVA 0.13 ± 0.11 0.07 to 0.37 0.12 ± 0.13 0.13 to 0.39 0.747 <0.001 <0.001 Photopic DCIVA 0.18 ± 0.09 0.03 to 0.37 0.18 ± 0.14 0.13 to 0.39 0.979 Mesopic DCIVA 0.37 ± 0.12 0.17 to 0.57 0.40 ± 0.11 0.07 to 0.59 0.274 Near Photopic UNVA 0.04 ± 0.06 0.06 to 0.20 0.04 ± 0.06 0.12 to 0.20 1.000 <0.001 <0.001 Photopic DCNVA 0.01 ± 0.05 0.12 to 0.14 0.02 ± 0.06 0.06 to 0.22 0.238 Mesopic DCNVA 0.13 ± 0.07 0.02 to 0.28 0.12 ± 0.07 0.00 to 0.30 0.796 CDVA indicates corrected distance visual acuity; DCIVA, distance-corrected intermediate visual acuity; DCNVA, distance-corrected near visual acuity; UDVA, uncorrected distance visual acuity; UIVA, uncorrected intermediate visual acuity; UNVA, uncorrected near visual acuity. *Comparison of the mean values between the 3- and 6-month visits. Comparison of the mean values between photopic and mesopic distance-corrected visual acuities at the 3-month visit. Comparison of the mean values between photopic and mesopic distance-corrected visual acuities at the 6-month visit. 24 (67%), and 25 subjects (69%) reported that it was easy/ very easy for them to perform distance, intermediate, and near activities without optical correction, respectively. Of 15 subjects, 13 (87%) who were drivers reported that it was easy/very easy for them to drive at night without optical correction whereas 1 (7%) reported that it was impossible to do so; 1 subject (7%) reported that she did not drive at that time. A total of 21 (58%), 21 (58%), and no subjects (0%) reported halo, glare, and double images/ ghosting, resepectively. For those experiencing halo and glare, 20 (95%) and 19 of them (90%) reported that it was not bothersome/ mildly bothersome. Among the 4 (11%) and 11 subjects (31%) who reported difficulty in seeing distance and reading small print, respectively all (100%) and 9 of them (82%) found it not bothersome/mildly bothersome. The change in response was not significant between the 3- and 6-month visits (P > 0.05 for all possible comparisons). Comparison Between Patients Who Underwent Presbyopic Lens Exchange and Cataract Extraction Sixteen subjects (44%) underwent bilateral presbyopic lens exchange whereas the remaining (56%) had unilateral or bilateral cataract extraction. The postoperative binocular UDVA, UIVA, and UNVA did not differ significantly between groups (P > 0.05 for all comparisons). The distribution in questionnaire responses did not differ significantly between groups (P > 0.05 for all comparisons). The only subject (3%) who regretted undergoing the surgery had bilateral cataract preoperatively. 16 www.apjo.org

Bifocal Diffractive IOL in Presbyopic Patients A B C D E F FIGURE 2. At 6-month visit: A, Monocular UDVA and CDVA (72 eyes). B, Binocular UDVA, CDVA, and mesopic CDVA (36 subjects). C, Monocular UIVA and DCIVA at 67 cm (72 eyes). D, Binocular UIVA, DCIVA, and mesopic DCIVA at 67 cm (36 subjects). E, Monocular UNVA and DCNVA at 33 cm (72 eyes). F, Binocular UNVA, DCNVA, and mesopic DCNVA (36 subjects) at 33 cm. CDVA indicates corrected distance visual acuity; DCIVA, distance-corrected intermediate visual acuity; DCNVA, distance-corrected near visual acuity; UDVA, uncorrected distance visual acuity; UIVA, uncorrected intermediate visual acuity; UNVA, uncorrected near visual acuity. www.apjo.org 17

Chang A B 2.50 2.50 2.00 2.00 Contrast Sensitivity (log10) 1.50 1.00 Contrast Sensitivity (log10) 1.50 1.00 ZMB00 (binocular photopic without glare) ZMB00 (binocular mesopic without glare) 0.50 Population norm (20-55 years old) (monocular photopic without glare) ZMB00 (binocular photopic with glare) 0.50 ZMB00 (binocular mesopic with glare) Population norm (50-75 years old) (monocular photopic without glare) Population norm (20-55 years old) (monocular mesopic without glare) 0 0 3 6 12 18 3 6 12 18 Spatial Frequency (Cycles Per Degree) Spatial Frequency (Cycles Per Degree) FIGURE 3. At 6-month visit (36 subjects): A, Mean binocular distance-corrected contrast sensitivity under photopic conditions without glare (diamonds) and with glare (squares), mean monocular population norm of 20- to 55-year-old individuals under photopic conditions (stars) (data from VectorVision 21 ), and mean monocular population norm of 50- to 75-year-old individuals under photopic conditions (plusses) (data from Pomerance and Evans 22 and VectorVision 21 ) at different spatial frequencies. B, Mean binocular distance-corrected contrast sensitivity under mesopic conditions without glare (triangles) and with glare (crosses), mean monocular population norm of 20- to 55-year-old individuals under mesopic conditions (circles) (data from VectorVision 21 ) at different spatial frequencies. DISCUSSION The implantation of MIOLs during cataract surgery and refractive lens exchange to treat presbyopia is increasingly common. Apart from traditional subjective parameters such as VA, surgeons and patients are concerned about the visual quality and photic phenomena because they also affect postoperative satisfaction. To obtain a better understanding on the performance of a particular MIOL in real-life situations, the implants should be studied under standardized photopic conditions and challenging conditions such as mesopic and glare conditions. The current mean monocular CDVA was 0.10 logmar (20/16), which was similar to the results achieved with the ZMB00 already reported [range, 0.03 to 0.08 logmar (20/21 to 20/16)]. 3,5 7,9,11 The current binocular CDVA was well maintained at 0.11 logmar (20/16) from photopic to mesopic conditions, which was consistent with the monocular findings that Schmickler et al 7 and Chang et al 10 reported. This might be the result of the pupil-independent design of the ZMB00. 7,10 The current mean monocular DCNVA was 0.06 logmar (20/23) at 33 cm. Previous studies of the ZMB00 have reported comparable DCNVAs of 0.15 to 0.01 logmar (20/28 to 20/20) at 30 to 40 cm or patient-preferred distance. 3,7,9 11 The current binocular DCNVA worsened significantly by 1 line from 0.02 to 0.12 logmar (20/20 to 20/26) from photopic to mesopic conditions. Other studies reported the same. 7,11 Worsening of up to 1 line can be considered clinically insignificant. The current mean monocular DCIVA was 0.31 logmar (20/41) at 67 cm, which was 1 and 2 lines worse than DCNVA and CDVA, respectively. The relatively poor intermediate VA is a well-known characteristic in bifocal MIOLs with high near addition because light is directed mainly to the distance and near foci. 16,17 Nevertheless, a VA of about 20/40 is still clinically useful. 10,18 Previous studies of the ZMB00 have also reported a monocular DCIVA similar to the current values, which ranged from 0.23 to 0.34 logmar (20/44 to 20/34) at 67 to 80 cm 10,11 ; a study reported a poor DCIVA of 0.54 logmar (20/69) but did not specify the working distance. 9 Binocular summation improved the intermediate VA under both photopic and mesopic conditions 11 ; this was also seen in the current study. The current CS was 3% to 6% better under photopic than mesopic conditions without glare and the difference was statistically significant at the spatial frequencies of 3, 6, and 12 cpd; the difference was less obvious with glare where photopic CS was better than mesopic CS by 3% to 6%, with a significant difference detected only at 12 cpd (CS data for each spatial frequency not shown). However, the CS with glare was significantly worse by 12% to 16% than without glare at all spatial frequencies, under both photopic and mesopic conditions (CS data for each spatial frequency not shown). In other words, low background lighting and glare resulted in poor CS, with glare being a more significant factor. Lubiński et al 8 who studied the ZMB00 had similar findings to the current results in that the CS worsened at various spatial frequencies by 2% to 9% when moving from photopic to mesopic 18 www.apjo.org

Bifocal Diffractive IOL in Presbyopic Patients TABLE 5. Questionnaire Results at the 3- and 6-Month Visits (36 Subjects) Question Followup, mo No. (%) of Patients P value* 1. Since your surgery, how satisfied have you been with your vision without contact lenses and/or glasses? Very Satisfied Satisfied Neutral Dissatisfied Very Dissatisfied A. During the day 3 13 (36) 21 (58) 1 (3) 1 (3) 0 (0) 0.317 6 16 (44) 18 (50) 1 (3) 1 (3) 0 (0) B. At night 3 9 (25) 23 (64) 4 (11) 0 (0) 0 (0) N/A 6 12 (33) 21 (58) 2 (6) 1 (3) 0 (0) C. Overall 3 10 (28) 24 (67) 1 (3) 1 (3) 0 (0) 0.319 6 13 (36) 20 (56) 2 (6) 1 (3) 0 (0) 2. Over the past month, how often did you wear the following to correct your vision? Never Hardly Ever Sometimes Often Always A. Glasses 3 31 (86) 1 (3) 2 (6) 0 (0) 2 (6) N/A 6 30 (83) 3 (8) 1 (3) 1 (3) 1 (3) B. Contact lens 3 36 (100) 0 (0) 0 (0) 0 (0) 0 (0) N/A 6 36 (100) 0 (0) 0 (0) 0 (0) 0 (0) 3. During the past month, how much more convenient has it been to see without glasses or contact lenses while performing your normal daily activities? 4. Does having intraocular lenses give you the freedom to perform multiple activities without depending upon glasses and/or contact lenses? Much More More The Same Less Much Less 3 31 (86) 4 (11) 1 (3) 0 (0) 0 (0) N/A 6 32 (89) 1 (3) 2 (6) 1 (3) 0 (0) Always Usually Sometimes Not Often Never 3 34 (94) 0 (0) 1 (3) 0 (0) 1 (3) N/A 6 34 (94) 1 (3) 1 (3) 0 (0) 0 (0) 5. Since your surgery, how easy is it to perform the following activities without glasses and/or contact lenses? Very Easy Easy Difficult Very Difficult Impossible A. Reading small print in dim lights 3 12 (33) 10 (28) 13 (36) 1 (3) 0 (0) 0.298 6 16 (44) 9 (25) 10 (28) 1 (3) 0 (0) B. Seeing at arm s length 3 8 (22) 13 (36) 13 (36) 1 (3) 1 (3) N/A 6 14 (39) 10 (28) 11 (31) 1 (3) 0 (0) C. Seeing far away 3 22 (61) 13 (36) 1 (3) 0 (0) 0 (0) 0.819 6 24 (67) 11 (31) 1 (3) 0 (0) 0 (0) D. Driving at night (15 patients) 3 6 (40) 5 (33) 2 (13) 0 (0) 2 (13) N/A 6 6 (40) 7 (47) 0 (0) 0 (0) 2 (13) 6. Since your surgery, how would you rate the distance at which it is comfortable for you to read? Much Too Close Slightly Too Close Perfect Slight Too Far Much Too Far 3 0 (0) 1 (3) 34 (94) 1 (3) 0 (0) N/A 6 0 (0) 0 (0) 36 (100) 0 (0) 0 (0) 7. How often have you been bothered by fluctuations in your vision when: Never Hardly Ever Sometimes Often Always A. Reading small print in dim lights 3 27 (75) 1 (3) 7 (19) 1 (3) 0 (0) 0.197 6 30 (83) 4 (11) 1 (3) 1 (3) 0 (0) B. Seeing at arm s length 3 30 (83) 3 (8) 1 (3) 1 (3) 1 (3) N/A 6 32 (89) 1 (3) 3 (8) 0 (0) 0 (0) C. Seeing far away 3 35 (97) 0 (0) 0 (0) 1 (3) 0 (0) N/A 6 35 (97) 0 (0) 1 (3) 0 (0) 0 (0) 8. Please indicate any of the following symptoms you currently experience related to your vision: Present But Not Bothersome Mildly Moderately Very Not Present Bothersome Bothersome Bothersome A. Halo around lights 3 10 (28) 23 (64) 3 (8) 0 (0) 0 (0) N/A 6 15 (42) 17 (47) 3 (8) 0 (0) 1 (3) B. Difficulty with glare at night 3 11 (31) 18 (50) 3 (8) 4 (11) 0 (0) 0.415 6 15 (42) 16 (44) 3 (8) 2 (6) 0 (0) C. Double images/ghosting 3 35 (97) 0 (0) 1 (3) 0 (0) 0 (0) N/A 6 36 (100) 0 (0) 0 (0) 0 (0) 0 (0) D. Difficulty reading small print 3 22 (61) 10 (28) 3 (8) 1 (3) 0 (0) 0.199 6 25 (69) 7 (19) 2 (6) 2 (6) 0 (0) E. Difficulty seeing far away 3 32 (89) 1 (3) 3 (8) 0 (0) 0 (0) 0.368 6 32 (89) 2 (6) 2 (6) 0 (0) 0 (0) 9. If given the opportunity, would you elect to be implanted with the same intraocular lenses? *Comparison of the mean values between the 3- and 6-month visits. McNemar-Bowker tests could not be performed with missing cells. Fifteen subjects (42%) were ever drivers at the 3- and/or 6-month visits. Definitely Most Likely Maybe Unlikely Definitely Not 3 32 (89) 3 (8) 0 (0) 0 (0) 1 (3) 0.607 6 32 (89) 3 (8) 0 (0) 0 (0) 1 (3) www.apjo.org 19

Chang conditions. However, Cochener 3 and Chaves et al 9 did not identify obvious or significant differences between photopic CS results with the ZMB00 with and without glare. It is noteworthy that the glare source was not the same among the current study and those of Cochener 3 and Chaves et al, 9 which might have contributed to the different findings. Baykara et al 19 used the same CSV- 1000HGT glare source as in the current study and reported that glare impaired the photopic CS by 5% to 12% after implantation of the Acriva UD Reviol MFB 625 MIOL (VSY Biotechnology BV, Amsterdam, The Netherlands). Hayashi et al 20 reported that a 200-lux glare source in the periphery at 20 degrees of the visual axis did not significantly impact the photopic contrast VA but did worsen the mesopic contrast VA significantly in patients with the ReSTOR SN6AD2 MIOL (Alcon Laboratories Inc). Therefore, we suggest that the effect of glare on the CS may not be straightforward and might be exaggerated by low lighting levels. Despite a poorer CS in challenging conditions, the current binocular CS was still within the population monocular norm in younger (20 55 years old) 21 and older patients (50 75 years old). 21,22 Recent development of MIOLs includes bifocal MIOLs with a lower near addition and trifocal MIOLs. Theoretically, the main advantage of these MIOLs is the improved intermediate vision. However, previous studies of bifocal MIOLs with lower near addition did not provide substantially better intermediate vision than those with higher near addition. 23 In addition, the near vision of these MIOLs could be less favorable than one with a higher near addition 23 because a lower near addition corresponds to a more distant focal point (eg, 53 cm for a +2.5 D near addition), which is not usually consistent with patients habitual reading distance. On the other hand, trifocal MIOLs had substantially better intermediate vision than high-addition bifocal MIOLs while maintaining good near vision. 24,25 A similar conclusion was also reported in a systematic review and meta-analysis by Shen et al. 26 The authors postulated that the additional intermediate focus in trifocal MIOLs may impact CS. However, they did not come to a conclusive result for the difference between bifocal and trifocal MIOLs. The current results showed that the ZMB00 stabilized as early as 3 months postoperatively, as reflected by the insignificant and minimal changes in refraction, VA, and CS between the 3- and 6-month postoperative time points. The single-piece design likely contributed to the axial positional stability. 27 Some items in the current questionnaire are worth highlighting because they affected high percentages of the subjects. First, 11 (31%) and 12 subjects (33%) reported difficulty reading small print and at arm s length, respectively, although 9 (82%) and 11 of them (92%) had binocular UNVA of 0.00 logmar (20/20) or better and binocular UIVA of 0.30 logmar (20/40) or better (question 5A and 5B). These results indicated that good VA with a MIOL is not always correlated with good visual quality. Second, visual symptoms such as halos and difficulty with glare occurred frequently in the current subjects [21 (58%) and 21 (58%), respectively] (question 8A and 8B). Most subjects reported halos [20 subjects (95%)] and glare at night [19 subjects (90%)] but described them as not or mildly bothersome. The outof-focus images produced by the multiple foci in MIOLs induce halos. 17,28 Chang 11 reported that 31% of patients undergoing ZMB00 implantation perceived halos and 60% of them described the symptoms as not or mildly bothersome, whereas Lubiński et al 8 reported that no patients with halos (60%) had severe symptoms with the ZMB00. The current CS results supported the questionnaire results as the mesopic CS with glare was still within the normal range. Informing patients preoperatively regarding the high incidence of halo and glare is very important. Patients who undergo presbyopic lens exchange generally have higher expectations than those with cataract and therefore may be less satisfied postoperatively because they have better preoperative CDVA. However, we did not find a significant difference in questionnaire responses using an ordinal scale in the current study. To reveal possible differences between groups, we dichotomized some of the questionnaire responses as an ancillary analysis. We found that a lower proportion of subjects were satisfied or very satisfied with their postoperative uncorrected vision in patients undergoing presbyopic lens exchange (88%) than cataract surgery (95%) (Fisher exact test, P = 0.574) despite a higher rate of complete spectacle independence (94% vs 75%) (Fisher exact test, P = 0.196). Notably, the difference in postoperative binocular uncorrected VA was clinically and statistically insignificant between both groups at distance [ 0.02 vs 0.07 logmar (20/19 vs 20/17)], intermediate [0.10 vs 0.15 logmar (20/25 vs 20/28)], and near [0.04 vs 0.04 logmar (20/22 vs 20/22)]. Additionally, halo was either not present or not bothersome in a similar proportion of subjects in both groups (88% vs 90%) (Fisher exact test, P = 1.000). Patients undergoing presbyopic lens exchange also had a lower proportion of subjects having difficulty with glare (75%) than cataract surgery (95%) (Fisher exact test, P = 0.149). In other words, surgeons should have thorough preoperative discussion with patients having good preoperative VA and manage their expectations. A 55-year-old female subject in the current study would not elect to implant the same MIOL if she could choose again. She was a low hyperope preoperatively, with a refraction of +0.50/+1.50 10 in the right eye and +1.50/+0.25 170 in the left eye and a CDVA of 0.10 logmar (20/25) bilaterally. She was dissatisfied with both daytime and overall vision (question 1A and 1C), and had difficulty reading small print in dim light (question 5A), inability to drive at night (question 5D), fluctuating vision at different distances (question 7A to 7C), very bothersome halos (question 8A), and moderately bothersome difficulty with glare at night (question 8B). Notably, her postoperative binocular UDVA, UIVA, and UNVA were 0.00 (20/20), 0.39 (20/49), and 0.28 logmar (20/31), respectively. The mesopic pupillary sizes were 4.0 mm bilaterally. The good VA did not explain why she complained of poor vision at different distances. The relatively small pupillary sizes also did not explain her difficulty performing various tasks at night. Apart from the good preoperative VA, it has been suggested that patients with mild refractive error also tend to have higher expectations after MIOL implantation. 29 Therefore, again, careful preoperative counseling remains an important component of postoperative satisfaction. There are limitations in the current study. First, both patients who underwent presbyopic lens exchange and cataract surgery were recruited. The heterogeneity in motivation and expectation between the 2 groups might have averaged out the satisfaction. Therefore, we compared the postoperative results between groups based on their preoperative CDVA, which served as a surrogate of motivation and expectation. The statistically insignificant difference between groups suggests that a larger sample size is needed in future study to confirm the findings for this 20 www.apjo.org

Bifocal Diffractive IOL in Presbyopic Patients MIOL. Second, we included both eyes for monocular analysis. Nonetheless, binocular analysis was the primary outcome, which reflects subjects ability to perform tasks in daily life. Third, the questionnaire is not validated. However, it covers aspects related to visual satisfaction, spectacle independence, ease of performing daily activities, and visual symptoms, which should have adequately reflected the quality of life of subjects who were implanted with the MIOL. In conclusion, bilateral implantation of the ZMB00 bifocal diffractive MIOL provided patients with good distance and near vision and satisfactory intermediate vision. Low lighting conditions affected distance and near vision minimally but reduced intermediate vision substantially. The CS with this MIOL worsened under low light conditions and in the presence of glare, but the interaction between these 2 factors has not yet been explored. Visual symptoms such as halos and difficulty with glare were commonly present but did not largely affect the subjective visual quality. 21 REFERENCES 1. Agresta B, Knorz MC, Kohnen T, et al. Distance and near visual acuity improvement after implantation of multifocal intraocular lenses in cataract patients with presbyopia: a systematic review. J Refract Surg. 2012;28: 426 435. 2. de Silva SR, Evans JR, Kirthi V, et al. Multifocal versus monofocal intraocular lenses after cataract extraction. Cochrane Database Syst Rev. 2016;12:CD003169. 3. Cochener B. Prospective clinical comparison of patient outcomes following implantation of trifocal or bifocal intraocular lenses. J Refract Surg. 2016;32:146 151. 4. Carson D, Hill WE, Hong X, et al. Optical bench performance of AcrySof IQ ReSTOR, AT LISA tri, and FineVision intraocular lenses. Clin Ophthalmol. 2014;8:2105 2113. 5. Bautista CP, González DC, Gómez AC. 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Clinical comparison of patient outcomes following implantation of trifocal or bifocal intraocular lenses: a systematic review and meta-analysis. Sci Rep. 2017;7:45337. 27. Zhong X, Long E, Chen W, et al. Comparisons of the in-the-bag stabilities of single-piece and three-piece intraocular lenses for age-related cataract patients: a randomized controlled trial. BMC Ophthalmol. 2016;16:100. 28. Puell MC, Pérez-Carrasco MJ, Hurtado-Ceña FJ, et al. Disk halo size measured in individuals with monofocal versus diffractive multifocal intraocular lenses. J Cataract Refract Surg. 2015;41:2417 2423. 29. Rosen E, Alió JL, Dick HB, et al. Efficacy and safety of multifocal intraocular lenses following cataract and refractive lens exchange: metaanalysis of peer-reviewed publications. J Cataract Refract Surg. 2016;42:310 328. www.apjo.org 21