Stability and clinical outcomes of a new one piece toric intraocular lens with anchor-wing haptics

Background: To evaluate the safety and e�cacy of a new toric intraocular lens (IOL) with anchor-wing haptics. Methods: The new toric IOL with anchor-wing haptics (NS60YT, NIDEK Co., Ltd.) was implanted in eligible patients with age-related cataracts with preoperative corneal astigmatism of 1.0 D or greater at a university hospital and two private hospitals in Japan. The following IOL cylinder powers were evaluated: 1.50 D (NS60YT3), 2.25 D (NS60YT4), 3.00 D (NS60YT5) and 4.50 D (NS60YT7). All patients were assessed out to 12 months postoperatively. The primary endpoint was uncorrected visual acuity (UCVA) with spherical addition at 6 months postoperatively, and the primary analysis calculated the proportion of eyes with UCVA with spherical addition of 0.1 logMAR or better. The magnitude of rotation was compared to the intended axis of IOL implantation at each postoperative examination. Adverse events were evaluated for the safety analysis. Results: This study enrolled 64 eyes of 53 patients. At 6 months postoperatively, for all IOL powers, UCVA with spherical addition of 0.1 logMAR or better was achieved in 90% [95% con�dence interval (CI): 80-96] of eyes. The mean IOL rotation was 5.3±4.3° at 12 months postoperatively. The mean magnitude of rotation ranged from 1.9° to 2.5° between each postoperative examination from 1 day to 12 months. There were no vision-threatening intraoperative or postoperative complications for the duration of the study. Conclusions: The NS60YT IOL remained stable after implantation and was e�cacious for treating 1.00 D or greater astigmatism in patients with senile cataracts.


Background
The reduction of astigmatism during cataract surgery is an important factor in visual function and postoperative patient satisfaction.Approximately 35% of patients with cataract have preoperative corneal astigmatism of 1.0 D or greater and approximately 20% have 1.5 D or greater astigmatism [1][2][3][4].Residual astigmatism after phacoemulsi cation and intraocular lens (IOL) implantation is a signi cant cause of suboptimal vision, increased spectacle dependence or patient dissatisfaction [5,6].There are a variety of methods currently used for treating cataracts with corneal astigmatism, including but not limited to, implantation of supplementary sulcus-xated IOLs, implantation of pinhole IOLs, or laser refractive surgery for a corneal "touch-up".The advantages of toric IOL implantation include a wider range of correction and the use of one procedure to simultaneously correct the refractive error, reducing the burden on the patient and the surgeon [7].
The Aktis toric (Model NS60YT; Nidek Co., Ltd.) is a newly developed IOL that is based on the existing monofocal Nex-Acri® AA 1P IOL platform (Nidek Co., Ltd.).Rotational stability for this IOL is maintained by anchor-wing haptics.In this prospective, multicenter study, we present the stability and clinical outcomes of NS60YT implantation for the correction of moderate to high astigmatism.

Methods
This single-arm, open-label, multicenter, prospective clinical study evaluated implantation of the NS60YT in patients with age-related cataracts at a university hospital and two private hospitals in Japan.This study was approved by the Jikei University Hospital Institutional Review Board for Medical Devices, the Sugita Eye Hospital Institutional Review Board, and the Joint Institutional Review Board of the hospitals.The study adhered to the Declaration of Helsinki and the Japanese Ministerial Ordinance on Good Clinical Practice for Medical Devices (GCP).This manuscript adheres to the CONSORT guidelines.The study protocol is available at https://clinicaltrials.gov.Written informed consent was obtained from all patients before participation.The study period was from December 2014 to November 2017.The duration of follow up was 12 months postoperatively.

Intraocular lens
The NS60YT is a single-piece toric IOL based on the Nex-Acri® series (Nidek Co., Ltd.) (Fig. 1).The optical diameter is 6.0 mm and the overall diameter is 13.0 mm including the anchor-wing haptics.The lens is a biconvex lens and the rear surface is aspheric (-0.15μm).The cylindrical power is placed on the front of the lens for the correction of corneal astigmatism.The IOL consists of hydrophobic soft acrylic resin with an ultraviolet absorber and proprietary material to enhance compatibility with the injector.The lens has two dots on either side of the optic periphery, indicating the attest meridian for marking the cylinder axis.This study evaluated 4 different toric IOL powers as follows: 1.50 D, 2.25 D, 3.00 D and 4.50 D (Table 1).

Patients
Patients were included if they were over 40 years old with age-related cataracts in one or both eyes with a pupil diameter of 5.0 mm or larger at mydriasis and had 1.0 D or greater preoperative corneal astigmatism.
Other inclusion criteria were, a predicted postoperative astigmatism less than 0.5 D, and the predicted postoperative uncorrected visual acuity (UCVA) with spherical addition of 0.1 logMAR or better."UCVA with spherical addition" is visual acuity measured under conditions where a spherical trial lens is added to correct the postoperative spherical refractive error determined before surgery for each patient.For example, when the target spherical refractive error is -1.5 D preoperatively, the visual acuity value measured with a -1.5 D spherical trial lens added postoperatively, is considered the "UCVA with spherical addition".
Patients were excluded if they had irregular corneal astigmatism, long axial length (28 mm or longer), and other diseases or complications that might affect the e cacy and safety of IOL implantation.

Calculation of intraocular lens power using a toric calculator
The IOL spherical power was selected by the surgeon based on the desired postoperative refractive error for each patient using the biometry values.The SRK/T formula was used for all eyes.The A-constants (119.7) were adjusted for each clinical site based on the constant for the Nex-Acri® AA 1P that is the same shape as NS60YT.The Nidek Toric Calculator For Clinical Trials was used to select cylinder power and to calculate the angle of implantation.Data entry of the preoperative corneal astigmatism, the surgically induced astigmatism for each surgeon, and the location of the incision allows calculation of the predicted postoperative corneal astigmatism, the IOL implantation axis, and the predicted postoperative residual astigmatism for each model.
Based on these variables, the surgeons selected the optimum IOL model that predicted the lowest postoperative astigmatism.

Surgery
Once the axis of implantation was veri ed with topographic data just prior to surgery, the patient was seated at a slit lamp and the surgeon used a gentian violet pen to mark the 3-o'clock, 6-o'clock and 9-o'clock positions.Intraoperatively, once the patient is supine and just prior to IOL implantation, the absence of head tilt is veri ed, and the gentian violet marks are used with a protracting device to nd the target meridian.All surgeries were performed with topical anesthesia using a sterile technique as follows: a 2.2 to 2.5 mm corneal, scleral or sclerocorneal incision was created and the cataractous lens was removed by phacoemulsi cation and aspiration, and an IOL was inserted into the lens capsule so that the toric marks on the IOL were aligned with the marks for axis alignment.An injector (Nex-IJ; Nidek Co., Ltd.) was used for IOL insertion.In patients scheduled for bilateral surgery, the fellow eye underwent surgery after the initial eye was evaluated at 1 week postoperatively and there were no complications.
The IOL axis was measured manually using slit lamp photography or from images obtained with anterior segment imaging devices (KATS-1000; Konan medical Co., Ltd. and Casia; Tomey Corp.).The patient was seated at the slit lamp and the correct head position (no tilt) was veri ed prior to acquiring photographs.
Deviation between the corneal astigmatic axis and the axis marks on the IOL was determined by using a protractor.The image was regarded as horizontal, and the angle was measured between the horizontal line and the toric mark.The patient questionnaire classi ed current vision into ve rankings as follows: "very satis ed", "satis ed", "neither satis ed nor dissatis ed", "dissatis ed", and "very dissatis ed".
Data were collected on all postoperative adverse events irrespective of causality.The following adverse events that may occur after cataract surgery were summarized as anticipated adverse events at every postoperative examination: secondary cataract (requiring posterior capsulotomy), macular degeneration, macular edema, hypopyon, infectious and noninfectious endophthalmitis, pupil block, retinal detachment, corneal edema, iritis, increased intraocular pressure (IOP), and IOL dislocation.Increased IOP was de ned as 23 mm Hg or higher and an increase of 5 mm Hg or higher compared to the preoperative IOP.

Statistical analysis
We used previous studies of toric IOLs that targetted emmetropia as the historical control to determine the number of cases that achieved a postoperative UCVA of 0.1 logMAR or better [8-10].The analysis indicated 47 eyes were required for NS60YT3, NS60YT4, NS60YT5 (signi cance level α = 0.05, power 1-β = 0.80), based on the threshold response rate (π0) 0.5 and the expected response rate (π1) 0.7.For high astigmatism (NS60YT7), data were collected on only 5 eyes due to the lack of appropriate patients.
The primary endpoint was the UCVA with spherical addition 6 months after surgery, and the primary analysis calculated the proportion of UCVA with spherical addition of 0.1 logMAR or better and a 95% con dence interval (CI).The Clopper-Pearson method was used to calculate 95% CIs.Secondary endpoints included UCVA, sphere-corrected VA, BCVA, refractive cylinder correction, and the magnitude of IOL rotation.Visual acuity was recorded in decimal notation at all sites, however for statistical analysis and consistency, all values were reported in logMAR.The magnitude of IOL rotation was calculated as the absolute value of the error between the actual IOL axis and preoperative IOL insertion axis calculated with the Nidek Toric Calculator For Clinical Trials.
Safety endpoints included the presence, absence, and incidence of adverse events after IOL insertion, and the presence or absence of anticipated adverse events.SAS (Version 9.3, SAS Institute Inc.) was used for statistical analysis.P < 0.05 was considered statistically signi cant.

Results
The study sample was comprised of 64 eyes of 53 patients.Two eyes of one patient were excluded from all analyses due to non-compliance with GCP.One patient died after 6 months examination due to reasons unrelated to cataract surgery.Therefore, the full analysis set for e cacy, included 62 eyes of 52 patients at 6 months postoperatively and 61 eyes of 51 patients at 12 months postoperatively.Table 2 presents patient demographics, baseline examination data and IOL calculation data.The mean age at enrollment was 68.6 ± 9.5 years (Table 2).The mean targeted postoperative refraction was -1.1 ± 1.2 D (Table 2).Primary endpoint -uncorrected visual acuity with spherical addition Table 3 presents the postoperative UCVA with spherical addition of 0.1 logMAR or better and the 95% CI.At 6 months, the primary endpoint was achieved in 90% (56/62 eyes) for all models, 100% (21/21 eyes), 80% (16/20 eyes), 93% (14/15 eyes), and 83% (5/6 eyes) for NS60YT3, NS60YT4, NS60YT5 and NS60YT7, respectively.At 12 months, 87% achieved the primary endpoint for all models.Fig. 2 presents the double angle polar plots.There were no remarkable changes observed between the preoperative corneal astigmatism (Fig. 2a) and the 12 months postoperative corneal astigmatism (Fig. 2b).
However, in eyes with subjective cylinder at 12 months postoperatively, the cylinder components tended towards against-the-rule (ATR) astigmatism (Fig. 2c).

Intraocular lens rotation (including additional analysis)
Fig. 3 presents the distribution of the rotation (absolute value) at 12 months compared to the axis of IOL insertion.A deviation less than 10° between the IOL axis and the insertion axis was noted in 89% (54/61 eyes) of all models.No cases required repositioning surgery due to postoperative IOL rotation.
Fig. 4 plots the postoperative changes in rotation relative to the insertion axis.The magnitude of rotation in all models was 5.5 ± 3.8° at 1 day, 5.6 ± 4.0° at 1 week, 5.1 ± 4.2° at 1 month, 5.4 ± 4.2° at 3 months, 5.0 ± 4.4° at 6 months, and 5.3 ± 4.3° at 12 months.Additional analysis indicated that the magnitude of rotation the day after surgery was 5.5°, and the mean rotation between each examination after day 1 was 2.5° or lower (Table 5).A rotation of 5.0° or more occurred in 52% by day 1, however, a rotation of 5.0° or more after day 1 was 7 to 13% for each period (Table 5).At 12 months postoperatively, the IOL rotated clockwise in 61% (37/61) of eyes, counterclockwise in 31% (19/61) of eyes, and the IOL did not rotate in 8% (5/61) of eyes.The direction of rotation and the preoperative corneal cylinder axis were not statistically associated (Fisher's exact test, P = 0.781).

Safety
Postoperative adverse events where a causal relationship could not be ruled out included 4 eyes (6%) with mild posterior capsule opaci cation.Anticipated adverse events (de ned separately at the beginning of the study) developed in 6 eyes of 5 patients.These included 2 eyes (3%) with secondary cataract (requiring posterior capsulotomy) and 4 eyes (6%) with increased IOP.One patient died during the course of the study due to multiple organ failure which was a non-ocular adverse event and had no causal relationship to cataract surgery or IOL implantation.

Discussion
This prospective evaluation of a new toric IOL (NS60YT) indicated the majority of eyes had excellent vision after cataract surgery.For example, BCVA at 12 months postoperatively was -0.10 ± 0.06 logMAR.The primary endpoint of the study was UCVA with spherical addition for this Japanese population.This index was used as the primary endpoint taking into consideration the tendency of lens selection in Japan.Japanese cataract patients tend to prefer some nearsightedness instead of emmetropia postoperatively.Using an UCVA with spherical addition as the primary endpoint enabled comparison with the published literature on toric IOLs targeting emmetropia despite targeting postoperative myopia (in the current study).
At 6 months postoperatively, 90% (56/62 eyes) of all eyes achieved UCVA with spherical addition of 0.1 logMAR or better.The lower limit (80%) of the 95% CI exceeded the expected response rate of 70%, which was the basis for determining the number of cases.This outcome indicates, that patients achieved equivalent or better postoperative visual acuity with the NS60YT in comparison with commercially available toric IOLs as the historical controls.
In contrast to the UCVA with spherical addition, sphere-corrected VA is the visual acuity obtained by further correcting the postoperative spherical refractive error only.In addition, the BCVA is the best visual acuity obtained by further correcting the residual postoperative cylindrical power from the sphere-corrected VA.This means that the difference between the UCVA with spherical addition and the sphere-corrected VA is the spherical refractive error with respect to the target refractive power.Additionally, the difference between the sphere-corrected VA and the BCVA is the cylindrical refractive error.Twelve months after surgery, the outcomes of the current study indicate a sphere-corrected VA of less than 0.1 logMAR in only one eye (2%), and 0.1 logMAR or better in the other 60 eyes (98%).This outcome indicates excellent cylinder correction with the NS60YT.
Vector analysis indicated that the postoperative subjective cylinder had a distribution toward ATR astigmatism.This trend is similar to the outcomes of wavefront analysis reported by Ninomiya et al [11].The primary cause of ATR astigmatism after surgery could be due to the effect of posterior corneal astigmatism.
As this study was designed in 2014, the protocol did not incorporate the effect of posterior corneal curvature.The current study used only the anterior corneal surface to evaluate corneal astigmatism, and the Nidek Toric Calculator For Clinical Trials did not consider the posterior corneal astigmatism for lens selection.Koch et al [12] have reported that posterior corneal astigmatism causes overcorrection of with-the-rule (WTR) astigmatism and decreases the correction of ATR astigmatism when the lens selection is based on the anterior corneal astigmatism only.Hence, our outcomes are consistent with Koch et al's observations [13].
Savini et al have published nomograms for selecting the IOL power when only the anterior corneal astigmatism is used.For preoperative WTR astigmatism, residual astigmatism is calculated based on the result from subtracting 0.59 D to 0.70 D from the predicted postoperative corneal astigmatism [14].For preoperative ATR astigmatism, residual astigmatism is calculated based on the result of adding 0.32 D to 0.70 D to the predicted postoperative corneal astigmatism [14].The current version of the Nidek Toric Calculator includes the Baylor nomogram to compensate for the posterior surface power when only anterior corneal surface data are used [12,13].
Accurate cylinder axis marking and rotational stability in the eye are important because the IOL correction of astigmatism decreases by 3.3% for an axial misalignment of 1°, and toric IOL implantation is completely ineffective when the misalignment is 30° or greater [15].The outcomes of the current study indicate the NS60YT has good rotational stability.For example, the mean IOL rotation at 6 months was 5.0 ± 4.4°for all models combined which is well within the range reported for other IOLs.Previous studies have reported rotation of single-piece toric IOLs between the intended axis and the observed axis from 2° to 9° at 6 months postoperatively [9,[16][17][18][19][20].Additionally, in the current study, the magnitude of rotation ranged from 1.9° to 2.5°b etween each postoperative examination from 1 day to 12 months and the mean rotation was 3.1± 2.9°.The tendency to rotate early in the postoperative period and then stabilize was similar to the previous literature on existing single-piece toric IOLs [21][22][23].
The anchor wing-haptic design contributes to the stability of the NS60YT toric IOL.The 90° orientation of the anchor wing-haptic design makes it di cult to generate a force in the rotational direction from compression due to the pressure from capsular contraction.Additionally, the width between the haptic shoulders is based on an average capsular diameter.The design geometry allows a secure t within the capsular bag using the shoulders to stabilize the IOL without relying on the overall haptics ('arms') of the IOL.Table 6 presents data on seven cases with a rotation of 10° or greater at 12 months postoperatively relative to the IOL insertion axis.Five cases (except Cases 3 and 4) rotated 10° or more at 1 day.In Case 4, a rotation of 10° or more was observed initially at 1 month.This case had an incomplete closed capsulorhexis with 2 tears.Perhaps postoperative healing and suboptimal capsular contraction due to the tears may have played a role in the rotation.Case 3 presented with a rotation of 10° or more initially at 12 months.The subsequent rotations were as follows: -4° at 1 week; -2° at 1 month; -9° at 3 months; -9° at 6 months; and -13° at 12 months.We are at a loss to explain the IOL rotation between visits.However we can rule out abnormal head positioning as experienced technicians, familiar with the equipment ensured the patient's head was in correct position prior to acquiring images.Although abnormal head position may have been missed at one visit, it would be highly unlikely in consecutive visits with the same patient.Additionally, the observation that the majority of patients were not symptomatic concurs with the low magnitude of rotation reported in the current study and indicates that relatively good image acquisition techniques and accurate measurements were used in the current study.
The cause of rotation in this case is unknown, however, the patient was asymptomatic and there were no postoperative sequelae.In these cases, the UCVA with spherical addition was 0.1 logMAR or better with Cases 2 and 4 excluded, and the sphere corrected VA was 0.05 logMAR or better with Case 2 excluded.Patient satisfaction with their vision remained high in all cases with a rotation of 10° or more.
This study evaluated the difference of the IOL axis at each postoperative examination relative to the insertion axis.Therefore, the evaluation included xed axis deviation of the IOL intraoperatively and the rotation from the early postoperative phase onwards.To verify the rotation from the insertion axis more accurately, the amount of rotation immediately after insertion of the IOL needs to be evaluated.
Design speci cations of the NS60YT intraocular lens The shape of anchor-wing haptics contributes to intraocular lens stability because it is di cult to generate a force in the rotational direction by compression.Additionally, the contact area in the capsule is large which contributes to good xational stability.

Table 1
Cylindrical power of each model of the NS60YT intraocular lens.

Table 2
Demographics and preoperative data of patients scheduled to undergo cataract surgery with implantation of the NS60YT intraocular lens.

Table 3
Uncorrected visual acuity with spherical addition of 0.1 logMAR or better, 6 and 12 months after cataract surgery with implantation of the NS60YT intraocular lens.

Table 4
Mean efficacy parameters for eyes that underwent cataract surgery with NS60YT intraocular lens implantation.

Table 5
Rotational stability of the NS60YT intraocular lens.

Table 6
Cases with rotation of 10° or greater at 12 months postoperatively.